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PODCAST: Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU

 

Progress in advanced prostate cancer has led to more personalized treatment options and individualized care for people with this diagnosis. Dr. Xin Gao discusses how the results of essential testing can help guide a patient’s prognosis and treatment path, reviews available therapies, and shares advice for self-advocacy.

Bio:
Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about Dr. Gao.

Download Resource Guide

See More From INSIST! Prostate Cancer

Transcript:

Katherine:

Hello and welcome. I’m your host Katherine Banwell. Today’s program focuses on how people with advanced prostate cancer can access the best treatment in care. We’ll review essential testing, discuss the latest research, and share tips for self-advocacy. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a resource guide. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Xin Gao. Dr. Gao, welcome. Would you please introduce yourself? 

Dr. Gao:

Yeah. Thank you very much for having me. My name is Xin Gao. I’m a medical oncologist at Mass General Cancer Center in Boston, Massachusetts. I focus on prostate cancer and other cancers involving the urinary system. I’m also involved in our clinical trials program where we’re studying newer and what we hope are better treatments for these types of cancers.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy guy.  

Dr. Gao:

I’m happy to be here.  

Katherine:

Good. Dr. Gao, this program is focusing on advanced prostate cancer. Would you walk us through how the disease progresses in each stage? 

Dr. Gao:

Sure. I think advanced prostate cancer can mean a lot of different things, but in general, it means a prostate cancer that has either spread out from the prostate gland itself to other areas of the body or has recurred despite either surgery or radiation-based therapy to the primary prostate tumor. 

In each of these situations, typically the focus would on medication types of treatments and we think about advanced prostate cancer as either hormone-sensitive or hormone-resistant, or the other term in the field for it would be castration-resistant, meaning that the prostate cancer is either sensitive to hormonal therapies or perhaps it’s no longer sensitive to the most common type of hormone therapy called androgen deprivation therapy. So, those are sort of the ways that the cancer can progress, and typically all these cancers start as hormone-sensitive prostate cancers and over time, they may evolve and become resistant and become what we call castration-resistant prostate cancer. 

Katherine:

Okay. So, they’re not numbered as in a lot of other cancers, like stage I, stage II?  

Dr. Gao:

Meaning by stage, oh. So, there are stages. All advanced prostate cancers are by definition stage IV. All advanced cancers, in general, are stage IV but advanced prostate cancer would be stage IV. Most prostate cancers actually present as localized prostate cancer, stage I, stage II, even stage III prostate cancers and the majority of localized prostate cancers are actually fortunately quite curable with either surgery or radiation-based therapies.  

Unfortunately, not all are curable and some will recur despite these curative intent treatments and others might just be inherently more aggressive biologically and they could even present with metastatic disease or stage IV disease having spread to other sites outside of the prostate gland, even at diagnosis. 

When prostate cancer metastasizes or spreads, it commonly spreads by lymphatic vessels or by the bloodstream and most commonly, they tend to go to either lymph nodes or bones or some combination of both. More common areas of lymph node spread are in the pelvic areas, kind of near where the prostate gland is, or deep in the abdomen in an area called the retroperitoneum. And then bones more commonly could be in sort of the back or spine bones or in the pelvic bones, but it could go to other areas less common as well.  

Katherine:

What are common symptoms of advanced disease, and how are the symptoms managed? 

Dr. Gao:

So, with advanced disease, the symptoms can present in a variety of different ways.  

They’re often related to where the cancer has spread to. If there’s a tumor in the prostate gland itself or next to it, some patients might experience urinary symptoms, urinary frequency, feeling of incomplete emptying or a weak urinary flow. Or even pain or discomfort of leading with urination. That’s sort of the primary prostate tumor itself. Bone metastases can cause bone pain and commonly this involves bones in the spine or back or in the pelvis.   

There’s also a heightened risk of fractures with bone metastases and obviously that can sometimes cause pain. However, I think I should mention, many bone metastases actually don’t cause pain. It’s not uncommon that we see a bone scan or a CAT scan that the cancer is in multiple bones, but the patient actually, you know, I think fortunately, doesn’t feel any pain from that. 

Lymph node spread, I would say, rarely causes symptoms early on, but if there’s significant enlargement of these lymph nodes or in risking anatomic areas, sometimes the lymph nodes can cause discomfort or pain. Sometimes they can compress upon major veins or blood vessels or on the ureters that drain the kidneys and cause either blood clots or lower extremity swelling if it’s the major veins or cause kidney dysfunction because the ureters aren’t draining the kidneys appropriately. And then, I think in general, as with any advanced cancer, advanced prostate cancer can commonly cause fatigue and cause patients to just kind of generally feel unwell in sort of a hard to pinpoint type of way.  

I think it’s sort of the general toll that the cancer – the burden of the cancer is causing on the body and maybe taking, you know, essential nutrients or other things away from normal body organs or body cells.  

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

So, pain, if people have pain, it’s typically managed with analgesics and pain medications, whether it’s Tylenol or ibuprofen. Other NSAID types of medications. Opiates and narcotic pain medications are commonly used for advanced prostate cancers as well to control and manage and treat the pain. And patients with cancers involving the bones that have become resistant to standard hormone therapy, we also commonly give medications called bisphosphonates. 

Zoledronic acid is a common one. Or a related medication called denosumab to try to reduce the risk of fractures, to strengthen the bones a bit. And these medications can also help with bone pain to some extent. And sometimes we treat other symptoms of cancer with medications that might help improve energy levels and improve the fatigue, for example.  

So, methylphenidate or methylphenidate  (Ritalin) is a common medication that is used to try to help with energy levels or reduced energy in advanced cancer patients. Sometimes steroid medications can do that as well, could be helpful. Appetite, reduced appetite with advanced cancer is not uncommon, although I think for prostate cancer, we see it to a lesser extent compared to other advanced cancers. 

There are other medications, steroids being one of them, and medications like mirtazapine or Remeron can be used to help try to simulate the appetite a little bit more. In terms of other symptoms, urinary symptoms, let’s say from the primary prostate tumor, that’s often co-managed with my colleagues in urology. There are medications that can be used to try to help with the urinary flow or stream in some situations or perhaps procedural interventions that might be able to help open up the urinary outlet a little bit more. Those things can be considered as well.  

Katherine:

I’d like to talk about what goes into deciding on a treatment pass. What testing is used to understand a patient’s individual disease? 

Dr. Gao:

There is a lot of testing that we do for – to try and characterize a patient’s individual disease and try to select an optimal management strategy for their specific cancer and their specific situation. 

We look at the biopsy, the pathology. The most common type of prostate cancer is called adenocarcinoma, but rarely we see certain other types under the microscope, things like neuroendocrine or small cell prostate cancers that tend to be treated in a different way. We look at things like the Gleason score.  

That tells us a bit more about sort of the aggressiveness of this cancer, as well as the PSA, you know, it’s a very good correlate for how the cancer is doing in general once somebody has been diagnosed with prostate cancer. For imaging tests, we commonly rely on imaging. We look at prostate MRIs to get an idea of the local extent of the prostate tumor. We get things like bone scans and CAT scans to look at the entire rest of the body to see if or where the cancer may have spread to.  

And there are newer imaging tests like the PSMA PET scan, which we commonly use now, which is a much more sensitive test for detecting prostate cancer in 2023 compared to traditional scans like CAT scans and bone scans. I also commonly make use of genetic testing and molecular information.  

So, for any patient with an advanced prostate cancer, I do recommend both what we call a germline test, which is testing for inherited cancer genes that a patient could have gotten from the parents and pass onto their kids, as well as somatic testing, which is testing the cancer itself to see what genetic mutations or alterations might’ve developed within their cancer. And that can actually factor into certain treatments that the patient may or may not be more likely to benefit from if they have these genetic mutations.  

Katherine:

Dr. Gao, a patient sent in this question prior to the program. What other genetic testing, beside BRCA markers, are important for deciding future targeted therapies and how are each of them used? 

Dr. Gao:

Yeah, that’s a great question. Targeted therapies have been used in a lot of different cancers and it’s only really within the past few years that we’re using them as a standard of care routinely in prostate cancers. So, BRCA II and BRCA I mutations are some of the more common mutations or genetic alterations that are targetable in prostate cancer. Recently, there have been multiple FDA approvals of different drugs that are called PARP inhibitor, which are able to target the cancer if they have BRCA II or BRCA I mutations.   

Beyond BRCA II and BRCA I, there’s a panel of what’s called homologous recombination repair genes and that’s defined differently in varying extents, depending on the specific drug. That has been FDA approved, but in general, it’s about 12-14 genes total and they actually include the BRCA II and BRCA I genes.  

So, some of the ones that have been…it seems like the data shows maybe more activity or better efficacy with these PARP inhibitors include a gene called PALB2, P-A-L-B 2. It’s not a very common mutation that we see, but it is something that we should look for because even if it’s not common overall for the patient who has it, it could be a very helpful and useful gene to know that that they have and it certainly would warrant treatment with a PARP inhibitor. 

The other sort of dozen  or so…10-12 genes in this homologous recombination repair pathway, the data, I would say, is still early and it is still somewhat limited in terms of how much people with those gene mutations truly benefit from these PARP inhibitors, but I do think it’s important to look for them, to know that if they do have one of these genetic mutations that it does make a PARP inhibitor an option for them. And then, beyond these HRR genes, I always look for something called a microsatellite instability or mismatched repair deficiency. These are sort of genetic features or really a panel of about four genes involved in a cellular process called – a DNA repair process called mismatch repair.  

For those patients that have either mismatched repair deficiency or microsatellite instability high cancers, I do recommend that they consider an immunotherapy medication called pembrolizumab which is FDA-approved regardless of cancer type for any MSI high or mismatched repair cancer and they’ve shown pretty solid activity for those kinds of cancers.  

Katherine:

Dr. Gao, now that we know what goes into understanding a patient’s disease, I’d like to talk about treatment, starting with treatment goals. How do goals vary by patient, if they vary at all? 

Dr. Gao:

Sure, yeah. I do think they vary and I think it is important to be clear about what the realistic goals of treatment might be so that the patient can make an informed decision on how the prostate cancer should be treated or managed. 

Some prostate cancers are highly curable, although there isn’t anything that’s 100 percent, right? And others are curable, but we acknowledge that there may still be a significant risk of relapse despite treatment. And maybe that rough percentage, the probability of cure and sort of the potential downsides or side effects of treatment, that’s something that the patient has to weigh in terms of whether they want to proceed with that treatment or not.  

And then, there are cancers, especially with advanced prostate cancers, that are unfortunately not curable, but yet treatments have the ability to significantly prolong somebody’s life, to slow the cancer progression down or even to shrink it, and to improve cancer-associated symptoms and other sources of distress that we talked about earlier. 

And so, with each patient, I think it is important to talk about these treatment goals because it may not be readily clear, is this a curable cancer or not? And it might not be clear how much benefit they might expect with treatment or are we talking about a marginal benefit? And then that way, you know, they can think about it, talk about it with their family, and kind of factor into their overall benefit risk calculation about whether to do something or not.  

Katherine:

Would you provide an overview of current treatment options for advanced disease? 

Dr. Gao:

Sure. So, it’s a big, very open-ended question, I think.  

So, I think you can divide it up into sort of the major treatment modalities, so things like radiation or radiation types of therapies, chemotherapy, hormonal therapies which are the mainstay of prostate cancer treatments, targeted therapies, and immunotherapies.   

Starting with hormonal therapies which are the backbone of prostate cancer treatments, for advanced prostate cancer, androgen deprivation therapy or ADT is often given indefinitely as the typical standard of care treatment and there are various forms of ADT, most commonly in the form of long-lasting injectable medications – leuprolide (Eligard/Lupron Depot), goserelin (Zoladex), sometimes degarelix (Firmagaon)  is used. And then more recently, there was an FDA approval a couple years ago of an oral pill called relugolix (Orgovyx), which is also a form of ADT or androgen deprivation therapy.   

These medications block the body’s ability to make testosterone which is important for prostate cancer survival and spread. In addition, abiraterone is an oral medication that is also considered a hormonal therapy. It blocks the production on androgens or male sex hormones outside of the testes. That includes the adrenal glands and some other tissues such as prostate cancer itself. And abiraterone (Zytiga) is commonly used in advanced prostate cancer management, in addition to androgen deprivation therapy whereas ADT blocks the testes from making testosterone and androgens, abiraterone blocks the production of androgens outside of the testes. 

And then finally, oral anti-androgen medications that block the prostate cancers from being able to detect androgens or male hormones and to block the androgen receptors on prostate cancers from sending cellular signals for growth and survival are also very commonly used.  

There are older anti-androgen medications like bicalutamide (Casodex), flutamide (Eulexin), lutamide, and there are newer ones, stronger versions, called enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). For most patients who present with advanced prostate cancer, I think this is much easier, ADT along with either abiraterone or one of the newer, stronger anti-androgens, is the standard of care for most advanced prostate cancer patients with metastatic disease.  

And then, sometimes for patients with higher volume or more aggressive cancers even in the group with metastatic disease, we even add on another treatment, usually chemotherapy, something called docetaxel for what we call triple therapy. And then, maybe that’s a segue to chemotherapy, so docetaxel chemotherapy is a common chemotherapy used for prostate cancer, certainly advanced prostate cancers. Cabazitaxel (Jevtana) is also a common chemotherapy in this situation. These two are related drugs in a family of drugs called taxane chemotherapies and basically they kind of block the trafficking of important components within cancer cells and cause the cancer cell death.  

Docetaxel (Taxotere) is the more commonly used one. It’s typically used earlier, before cabazitaxel. And like I said earlier, for certain patients with what we call high volume metastatic prostate cancer, it’s often used in combination with hormonal therapies early on, what we call upfront therapy for six cycles. If a patient doesn’t receive docetaxel up front, docetaxel is commonly used after progression, after the cancer has progressed on ADT and one of the oral hormone medications.  

Cabazitaxel is more commonly used after a patient has previously received or progressed on docetaxel. Both drugs have been evaluated in randomized Phase III clinical trials and have shown to provide efficacy for patients with advanced prostate cancers. 

In addition to these taxane chemotherapies, platinum chemotherapy, such as carboplatin or cisplatin, are sometimes used for advanced prostate cancers as well, especially for certain neuroendocrine or small cell prostate cancers. These are rarer cancers, but they tend to respond better to platinum-based chemotherapies.  

Or for certain what we call aggressive variant prostate cancers, these platinum-based chemotherapies are also used in combination with either one of the taxanes or with another chemotherapy drug called etoposide. In terms of other treatment modalities, I think recently what we call radiotherapeutics or radioligand therapies have gotten a lot of press with the approval of a new medication called lutetium PSMA or 177 lutetium PSMA 617 (Pluvicto). 

The brand name for that in the U.S. is Pluvicto and what this is is a drug that’s a small molecule that binds to PSMA, which is a protein highly expressed in close to 90% of prostate cancer, advanced prostate cancers. And the small molecule will home to the cancer and it’s linked to radioactive lutetium and the lutetium will decay in that area and lead to cancer cell death.  

So, Pluvicto or lutetium was FDA approved in spring of 2022 based on randomized Phase III trials that show significant efficacy for patients with metastatic castration-resistant prostate cancer who have previously received a second-generation androgen receptor pathway inhibitor, such as abiraterone and enzalutamide, as well as a taxane chemotherapy, like docetaxel or cabazitaxel.  

The medication is given intravenously, once every six weeks, for up to six doses, and there are ongoing clinical trials, actually, that are trying to evaluate this medication in earlier settings where patients haven’t gotten prior chemotherapy before. There was a press release from about half a year ago stating that they’re seeing some early encouraging signs of efficacy with this drug, even in patients who had never received chemotherapy before, so it may be a medication that is going to be used more and more so in more patients even earlier in their course of disease. 

Katherine:

This actually leads me to my next question which is about research news. 

Prostate cancer research is evolving quickly, like so many other cancers. And it’s important for patients to stay up to date on developing news. So, are there research advances that patients should be aware of? 

Dr. Gao:

Yeah, I mean some of the treatments that I just mentioned, PARP inhibitors, pembrolizumab (Keytruda) for MSI higher and mismatch repair deficient tumors and lutetium. Those have come out of recent major clinical trials and have become the standard of care in a lot of different…in various different settings for patients. And there are always new research trials, clinical trials, that are going to either move some of these established treatments to earlier lines of setting, earlier lines of treatment, or using them in maybe combination with other drugs where we might learn that they’re more useful if we combine it with another drug or maybe combine it with hormone treatments earlier rather than later. 

So, there are always clinical trials for advanced prostate cancer. There are even newer trials, novel therapies, completely new treatments that have been studied in the laboratory in say petri dish models of cancer or animal, mouse models of prostate cancer, but have shown enough early exciting data to try to move them into human beings and hopefully help advanced prostate cancer patients. 

Katherine:

Dr. Gao, if a patient is feeling like they’re not getting proper care or if they’re just not comfortable with their care team, what steps would you recommend they take to change the situation? 

Dr. Gao:

Yeah, I think that’s a difficult question to answer and it depends on sort of what the specifics are, but I will always encourage people to be up front with their providers, with their oncologists and their oncology team. I think it’s… it really is a collaboration and it really needs mutual trust and open communication.  

And to be able to say these are the things that I wish could be a bit better or not that different or could you clarify this or answer this or what about this idea or this thing that maybe I heard about. See what their thoughts are. I think clear communication is always important and it shouldn’t – I tell my patients that I view my role as sort of advising them about what the reasonable treatment or management strategies might be in their situation and what the data shows and what is recommended. 

But ultimately, it is a shared decision and the patient is in charge of their own body and own health and they can make the decision on what makes sense for them. So, again, I think it’ s a two-way street and open communication is the most important thing.  

Katherine:

As we wrap up, Dr. Gao, I’d like to get your thoughts. How do you feel about where we stand with advanced prostate cancer care? 

Dr. Gao:

Yeah. I think there have been a lot of advances in advanced prostate cancer care in recent years. Newer and better treatment strategies seem to come along every couple of years and I think what we’ve seen for advanced prostate cancer patients over the past, really, since probably 2015 or so, is a significant improvement in outcomes, long-term outcomes like survival and slowing down of the cancer. 

And it’s… I think it’s important to acknowledge that and to acknowledge that the clinical trials in recent years have really led to a lot of improvements and really the hope that in the coming years, there’s going to be additional research, additional clinical trials, newer treatments hopefully, that will continue to improve outcomes for advanced prostate cancer patients. I also think that it’s really critical to evaluate the specific patients’ cancer characteristics, things like the genetic testing that I mentioned earlier, as well as their sort of life situations and other medical comorbidities to come to a shared decision about what makes the most sense in terms of their cancer management.  

Genetic testing might open up the option for certain FDA-approved therapies or consideration of certain targeted therapies that still might be in clinical trials. And clinical trials, again, are also an option for additional treatment strategies that otherwise would not be available. 

Katherine:

Dr. Gao, thank you so much for taking the time to join us today. 

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this program. It will help us as we plan future webinars. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. 

Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU

Advanced Prostate Cancer: How to Access the Best Care and Treatment for YOU from Patient Empowerment Network on Vimeo.

Progress in advanced prostate cancer has led to more personalized treatment options and individualized care for people with this diagnosis. Dr. Xin Gao discusses how the results of essential testing can help guide a patient’s prognosis and treatment path, reviews available therapies, and shares advice for self-advocacy.

Bio:
Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about Dr. Gao.

Download Resource Guide

See More From INSIST! Prostate Cancer

Related Resources

Prostate Cancer Research | Updates From ASCO 2023

Prostate Cancer Research Updates from ASCO 2023

What Key Factors Impact Prostate Cancer Treatment Decisions?

What Key Factors Impact Prostate Cancer Treatment Decisions?

What Are Current Prostate Cancer Treatment Options?

What Are Current Prostate Cancer Treatment Options?


Transcript:

Katherine:

Hello and welcome. I’m your host Katherine Banwell. Today’s program focuses on how people with advanced prostate cancer can access the best treatment in care. We’ll review essential testing, discuss the latest research, and share tips for self-advocacy. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to a resource guide. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Xin Gao. Dr. Gao, welcome. Would you please introduce yourself? 

Dr. Gao:

Yeah. Thank you very much for having me. My name is Xin Gao. I’m a medical oncologist at Mass General Cancer Center in Boston, Massachusetts. I focus on prostate cancer and other cancers involving the urinary system. I’m also involved in our clinical trials program where we’re studying newer and what we hope are better treatments for these types of cancers.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy guy.  

Dr. Gao:

I’m happy to be here.  

Katherine:

Good. Dr. Gao, this program is focusing on advanced prostate cancer. Would you walk us through how the disease progresses in each stage? 

Dr. Gao:

Sure. I think advanced prostate cancer can mean a lot of different things, but in general, it means a prostate cancer that has either spread out from the prostate gland itself to other areas of the body or has recurred despite either surgery or radiation-based therapy to the primary prostate tumor. 

In each of these situations, typically the focus would on medication types of treatments and we think about advanced prostate cancer as either hormone-sensitive or hormone-resistant, or the other term in the field for it would be castration-resistant, meaning that the prostate cancer is either sensitive to hormonal therapies or perhaps it’s no longer sensitive to the most common type of hormone therapy called androgen deprivation therapy. So, those are sort of the ways that the cancer can progress, and typically all these cancers start as hormone-sensitive prostate cancers and over time, they may evolve and become resistant and become what we call castration-resistant prostate cancer. 

Katherine:

Okay. So, they’re not numbered as in a lot of other cancers, like stage I, stage II?  

Dr. Gao:

Meaning by stage, oh. So, there are stages. All advanced prostate cancers are by definition stage IV. All advanced cancers, in general, are stage IV but advanced prostate cancer would be stage IV. Most prostate cancers actually present as localized prostate cancer, stage I, stage II, even stage III prostate cancers and the majority of localized prostate cancers are actually fortunately quite curable with either surgery or radiation-based therapies.  

Unfortunately, not all are curable and some will recur despite these curative intent treatments and others might just be inherently more aggressive biologically and they could even present with metastatic disease or stage IV disease having spread to other sites outside of the prostate gland, even at diagnosis. 

When prostate cancer metastasizes or spreads, it commonly spreads by lymphatic vessels or by the bloodstream and most commonly, they tend to go to either lymph nodes or bones or some combination of both. More common areas of lymph node spread are in the pelvic areas, kind of near where the prostate gland is, or deep in the abdomen in an area called the retroperitoneum. And then bones more commonly could be in sort of the back or spine bones or in the pelvic bones, but it could go to other areas less common as well.  

Katherine:

What are common symptoms of advanced disease, and how are the symptoms managed? 

Dr. Gao:

So, with advanced disease, the symptoms can present in a variety of different ways.  

They’re often related to where the cancer has spread to. If there’s a tumor in the prostate gland itself or next to it, some patients might experience urinary symptoms, urinary frequency, feeling of incomplete emptying or a weak urinary flow. Or even pain or discomfort of leading with urination. That’s sort of the primary prostate tumor itself. Bone metastases can cause bone pain and commonly this involves bones in the spine or back or in the pelvis.   

There’s also a heightened risk of fractures with bone metastases and obviously that can sometimes cause pain. However, I think I should mention, many bone metastases actually don’t cause pain. It’s not uncommon that we see a bone scan or a CAT scan that the cancer is in multiple bones, but the patient actually, you know, I think fortunately, doesn’t feel any pain from that. 

Lymph node spread, I would say, rarely causes symptoms early on, but if there’s significant enlargement of these lymph nodes or in risking anatomic areas, sometimes the lymph nodes can cause discomfort or pain. Sometimes they can compress upon major veins or blood vessels or on the ureters that drain the kidneys and cause either blood clots or lower extremity swelling if it’s the major veins or cause kidney dysfunction because the ureters aren’t draining the kidneys appropriately. And then, I think in general, as with any advanced cancer, advanced prostate cancer can commonly cause fatigue and cause patients to just kind of generally feel unwell in sort of a hard to pinpoint type of way.  

I think it’s sort of the general toll that the cancer – the burden of the cancer is causing on the body and maybe taking, you know, essential nutrients or other things away from normal body organs or body cells.  

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

So, pain, if people have pain, it’s typically managed with analgesics and pain medications, whether it’s Tylenol or ibuprofen. Other NSAID types of medications. Opiates and narcotic pain medications are commonly used for advanced prostate cancers as well to control and manage and treat the pain. And patients with cancers involving the bones that have become resistant to standard hormone therapy, we also commonly give medications called bisphosphonates. 

Zoledronic acid is a common one. Or a related medication called denosumab to try to reduce the risk of fractures, to strengthen the bones a bit. And these medications can also help with bone pain to some extent. And sometimes we treat other symptoms of cancer with medications that might help improve energy levels and improve the fatigue, for example.  

So, methylphenidate or methylphenidate  (Ritalin) is a common medication that is used to try to help with energy levels or reduced energy in advanced cancer patients. Sometimes steroid medications can do that as well, could be helpful. Appetite, reduced appetite with advanced cancer is not uncommon, although I think for prostate cancer, we see it to a lesser extent compared to other advanced cancers. 

There are other medications, steroids being one of them, and medications like mirtazapine or Remeron can be used to help try to simulate the appetite a little bit more. In terms of other symptoms, urinary symptoms, let’s say from the primary prostate tumor, that’s often co-managed with my colleagues in urology. There are medications that can be used to try to help with the urinary flow or stream in some situations or perhaps procedural interventions that might be able to help open up the urinary outlet a little bit more. Those things can be considered as well.  

Katherine:

I’d like to talk about what goes into deciding on a treatment pass. What testing is used to understand a patient’s individual disease? 

Dr. Gao:

There is a lot of testing that we do for – to try and characterize a patient’s individual disease and try to select an optimal management strategy for their specific cancer and their specific situation. 

We look at the biopsy, the pathology. The most common type of prostate cancer is called adenocarcinoma, but rarely we see certain other types under the microscope, things like neuroendocrine or small cell prostate cancers that tend to be treated in a different way. We look at things like the Gleason score.  

That tells us a bit more about sort of the aggressiveness of this cancer, as well as the PSA, you know, it’s a very good correlate for how the cancer is doing in general once somebody has been diagnosed with prostate cancer. For imaging tests, we commonly rely on imaging. We look at prostate MRIs to get an idea of the local extent of the prostate tumor. We get things like bone scans and CAT scans to look at the entire rest of the body to see if or where the cancer may have spread to.  

And there are newer imaging tests like the PSMA PET scan, which we commonly use now, which is a much more sensitive test for detecting prostate cancer in 2023 compared to traditional scans like CAT scans and bone scans. I also commonly make use of genetic testing and molecular information.  

So, for any patient with an advanced prostate cancer, I do recommend both what we call a germline test, which is testing for inherited cancer genes that a patient could have gotten from the parents and pass onto their kids, as well as somatic testing, which is testing the cancer itself to see what genetic mutations or alterations might’ve developed within their cancer. And that can actually factor into certain treatments that the patient may or may not be more likely to benefit from if they have these genetic mutations.  

Katherine:

Dr. Gao, a patient sent in this question prior to the program. What other genetic testing, beside BRCA markers, are important for deciding future targeted therapies and how are each of them used? 

Dr. Gao:

Yeah, that’s a great question. Targeted therapies have been used in a lot of different cancers and it’s only really within the past few years that we’re using them as a standard of care routinely in prostate cancers. So, BRCA II and BRCA I mutations are some of the more common mutations or genetic alterations that are targetable in prostate cancer. Recently, there have been multiple FDA approvals of different drugs that are called PARP inhibitor, which are able to target the cancer if they have BRCA II or BRCA I mutations.   

Beyond BRCA2 and BRCA1, there’s a panel of what’s called homologous recombination repair genes and that’s defined differently in varying extents, depending on the specific drug. That has been FDA approved, but in general, it’s about 12-14 genes total and they actually include the BRCA2 and BRCA1 genes.  

So, some of the ones that have been…it seems like the data shows maybe more activity or better efficacy with these PARP inhibitors include a gene called PALB2, P-A-L-B 2. It’s not a very common mutation that we see, but it is something that we should look for because even if it’s not common overall for the patient who has it, it could be a very helpful and useful gene to know that that they have and it certainly would warrant treatment with a PARP inhibitor. 

The other sort of dozen  or so…10-12 genes in this homologous recombination repair pathway, the data, I would say, is still early and it is still somewhat limited in terms of how much people with those gene mutations truly benefit from these PARP inhibitors, but I do think it’s important to look for them, to know that if they do have one of these genetic mutations that it does make a PARP inhibitor an option for them. And then, beyond these HRR genes, I always look for something called a microsatellite instability or mismatched repair deficiency. These are sort of genetic features or really a panel of about four genes involved in a cellular process called – a DNA repair process called mismatch repair.  

For those patients that have either mismatched repair deficiency or microsatellite instability high cancers, I do recommend that they consider an immunotherapy medication called pembrolizumab which is FDA-approved regardless of cancer type for any MSI high or mismatched repair cancer and they’ve shown pretty solid activity for those kinds of cancers.  

Katherine:

Dr. Gao, now that we know what goes into understanding a patient’s disease, I’d like to talk about treatment, starting with treatment goals. How do goals vary by patient, if they vary at all? 

Dr. Gao:

Sure, yeah. I do think they vary and I think it is important to be clear about what the realistic goals of treatment might be so that the patient can make an informed decision on how the prostate cancer should be treated or managed. 

Some prostate cancers are highly curable, although there isn’t anything that’s 100 percent, right? And others are curable, but we acknowledge that there may still be a significant risk of relapse despite treatment. And maybe that rough percentage, the probability of cure and sort of the potential downsides or side effects of treatment, that’s something that the patient has to weigh in terms of whether they want to proceed with that treatment or not.  

And then, there are cancers, especially with advanced prostate cancers, that are unfortunately not curable, but yet treatments have the ability to significantly prolong somebody’s life, to slow the cancer progression down or even to shrink it, and to improve cancer-associated symptoms and other sources of distress that we talked about earlier. 

And so, with each patient, I think it is important to talk about these treatment goals because it may not be readily clear, is this a curable cancer or not? And it might not be clear how much benefit they might expect with treatment or are we talking about a marginal benefit? And then that way, you know, they can think about it, talk about it with their family, and kind of factor into their overall benefit risk calculation about whether to do something or not.  

Katherine:

Would you provide an overview of current treatment options for advanced disease? 

Dr. Gao:

Sure. So, it’s a big, very open-ended question, I think.  

So, I think you can divide it up into sort of the major treatment modalities, so things like radiation or radiation types of therapies, chemotherapy, hormonal therapies which are the mainstay of prostate cancer treatments, targeted therapies, and immunotherapies.   

Starting with hormonal therapies which are the backbone of prostate cancer treatments, for advanced prostate cancer, androgen deprivation therapy or ADT is often given indefinitely as the typical standard of care treatment and there are various forms of ADT, most commonly in the form of long-lasting injectable medications – leuprolide (Eligard/Lupron Depot), goserelin (Zoladex), sometimes degarelix (Firmagaon)  is used. And then more recently, there was an FDA approval a couple years ago of an oral pill called relugolix (Orgovyx), which is also a form of ADT or androgen deprivation therapy.   

These medications block the body’s ability to make testosterone which is important for prostate cancer survival and spread. In addition, abiraterone is an oral medication that is also considered a hormonal therapy. It blocks the production on androgens or male sex hormones outside of the testes. That includes the adrenal glands and some other tissues such as prostate cancer itself. And abiraterone (Zytiga) is commonly used in advanced prostate cancer management, in addition to androgen deprivation therapy whereas ADT blocks the testes from making testosterone and androgens, abiraterone blocks the production of androgens outside of the testes. 

And then finally, oral anti-androgen medications that block the prostate cancers from being able to detect androgens or male hormones and to block the androgen receptors on prostate cancers from sending cellular signals for growth and survival are also very commonly used.  

There are older anti-androgen medications like bicalutamide (Casodex), flutamide (Eulexin), lutamide, and there are newer ones, stronger versions, called enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). For most patients who present with advanced prostate cancer, I think this is much easier, ADT along with either abiraterone or one of the newer, stronger anti-androgens, is the standard of care for most advanced prostate cancer patients with metastatic disease.  

And then, sometimes for patients with higher volume or more aggressive cancers even in the group with metastatic disease, we even add on another treatment, usually chemotherapy, something called docetaxel for what we call triple therapy. And then, maybe that’s a segue to chemotherapy, so docetaxel chemotherapy is a common chemotherapy used for prostate cancer, certainly advanced prostate cancers. Cabazitaxel (Jevtana) is also a common chemotherapy in this situation. These two are related drugs in a family of drugs called taxane chemotherapies and basically they kind of block the trafficking of important components within cancer cells and cause the cancer cell death.  

Docetaxel (Taxotere) is the more commonly used one. It’s typically used earlier, before cabazitaxel. And like I said earlier, for certain patients with what we call high volume metastatic prostate cancer, it’s often used in combination with hormonal therapies early on, what we call upfront therapy for six cycles. If a patient doesn’t receive docetaxel up front, docetaxel is commonly used after progression, after the cancer has progressed on ADT and one of the oral hormone medications.  

Cabazitaxel is more commonly used after a patient has previously received or progressed on docetaxel. Both drugs have been evaluated in randomized Phase III clinical trials and have shown to provide efficacy for patients with advanced prostate cancers. 

In addition to these taxane chemotherapies, platinum chemotherapy, such as carboplatin or cisplatin, are sometimes used for advanced prostate cancers as well, especially for certain neuroendocrine or small cell prostate cancers. These are rarer cancers, but they tend to respond better to platinum-based chemotherapies.  

Or for certain what we call aggressive variant prostate cancers, these platinum-based chemotherapies are also used in combination with either one of the taxanes or with another chemotherapy drug called etoposide. In terms of other treatment modalities, I think recently what we call radiotherapeutics or radioligand therapies have gotten a lot of press with the approval of a new medication called lutetium PSMA or 177 lutetium PSMA 617 (Pluvicto). 

The brand name for that in the U.S. is Pluvicto and what this is is a drug that’s a small molecule that binds to PSMA, which is a protein highly expressed in close to 90 percent of prostate cancer, advanced prostate cancers. And the small molecule will home to the cancer and it’s linked to radioactive lutetium and the lutetium will decay in that area and lead to cancer cell death.  

So, Pluvicto or lutetium was FDA approved in spring of 2022 based on randomized Phase III trials that show significant efficacy for patients with metastatic castration-resistant prostate cancer who have previously received a second-generation androgen receptor pathway inhibitor, such as abiraterone and enzalutamide, as well as a taxane chemotherapy, like docetaxel or cabazitaxel.  

The medication is given intravenously, once every six weeks, for up to six doses, and there are ongoing clinical trials, actually, that are trying to evaluate this medication in earlier settings where patients haven’t gotten prior chemotherapy before. There was a press release from about half a year ago stating that they’re seeing some early encouraging signs of efficacy with this drug, even in patients who had never received chemotherapy before, so it may be a medication that is going to be used more and more so in more patients even earlier in their course of disease. 

Katherine:

This actually leads me to my next question which is about research news. 

Prostate cancer research is evolving quickly, like so many other cancers. And it’s important for patients to stay up to date on developing news. So, are there research advances that patients should be aware of? 

Dr. Gao:

Yeah, I mean some of the treatments that I just mentioned, PARP inhibitors, pembrolizumab (Keytruda) for MSI higher and mismatch repair deficient tumors and lutetium. Those have come out of recent major clinical trials and have become the standard of care in a lot of different…in various different settings for patients. And there are always new research trials, clinical trials, that are going to either move some of these established treatments to earlier lines of setting, earlier lines of treatment, or using them in maybe combination with other drugs where we might learn that they’re more useful if we combine it with another drug or maybe combine it with hormone treatments earlier rather than later. 

So, there are always clinical trials for advanced prostate cancer. There are even newer trials, novel therapies, completely new treatments that have been studied in the laboratory in say petri dish models of cancer or animal, mouse models of prostate cancer, but have shown enough early exciting data to try to move them into human beings and hopefully help advanced prostate cancer patients. 

Katherine:

Dr. Gao, if a patient is feeling like they’re not getting proper care or if they’re just not comfortable with their care team, what steps would you recommend they take to change the situation? 

Dr. Gao:

Yeah, I think that’s a difficult question to answer and it depends on sort of what the specifics are, but I will always encourage people to be up front with their providers, with their oncologists and their oncology team. I think it’s… it really is a collaboration and it really needs mutual trust and open communication.  

And to be able to say these are the things that I wish could be a bit better or not that different or could you clarify this or answer this or what about this idea or this thing that maybe I heard about. See what their thoughts are. I think clear communication is always important and it shouldn’t – I tell my patients that I view my role as sort of advising them about what the reasonable treatment or management strategies might be in their situation and what the data shows and what is recommended. 

But ultimately, it is a shared decision and the patient is in charge of their own body and own health and they can make the decision on what makes sense for them. So, again, I think it’ s a two-way street and open communication is the most important thing.  

Katherine:

As we wrap up, Dr. Gao, I’d like to get your thoughts. How do you feel about where we stand with advanced prostate cancer care? 

Dr. Gao:

Yeah. I think there have been a lot of advances in advanced prostate cancer care in recent years. Newer and better treatment strategies seem to come along every couple of years and I think what we’ve seen for advanced prostate cancer patients over the past, really, since probably 2015 or so, is a significant improvement in outcomes, long-term outcomes like survival and slowing down of the cancer. 

And it’s… I think it’s important to acknowledge that and to acknowledge that the clinical trials in recent years have really led to a lot of improvements and really the hope that in the coming years, there’s going to be additional research, additional clinical trials, newer treatments hopefully, that will continue to improve outcomes for advanced prostate cancer patients. I also think that it’s really critical to evaluate the specific patients’ cancer characteristics, things like the genetic testing that I mentioned earlier, as well as their sort of life situations and other medical comorbidities to come to a shared decision about what makes the most sense in terms of their cancer management.  

Genetic testing might open up the option for certain FDA-approved therapies or consideration of certain targeted therapies that still might be in clinical trials. And clinical trials, again, are also an option for additional treatment strategies that otherwise would not be available. 

Katherine:

Dr. Gao, thank you so much for taking the time to join us today. 

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this program. It will help us as we plan future webinars. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. 

PODCAST: What Do You Need to Know About Emerging Endometrial Cancer Research?

 

Endometrial cancer treatment and research is evolving quickly. Dr. Emily Ko provides an update on new and emerging approaches, explains how these therapies work to treat endometrial cancer, and shares tips for partnering with your team on key decisions.
 
Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.

See More from Evolve Endometrial Cancer

Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with endometrial cancer learn more about evolving research and treatments. We’re also going to discuss how patients can collaborate with their team on care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. 

At the end of the program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Emily Ko. Dr. Ko, welcome. Would you please introduce yourself? 

Dr. Ko:

Surely. Thank you so much. My name is Dr. Emily Ko, and I am a gynecologic oncologist. Currently, I’m an associate professor at the University of Pennsylvania, and as part of my daily work, I see patients, I provide surgical and medical treatments for gynecologic cancers, and I also am a researcher involved particularly in endometrial cancer. 

Katherine:

Thank you so much for taking the time out of your schedule to join us today. 

Dr. Ko:

Thank you. 

Katherine:

Well, let’s start by learning about the latest research news. Just this June, endometrial cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology meeting, or ASCO, in Chicago. Can you walk us through the highlights that patients should know about? 

Dr. Ko:

Sure. So, the ASCO meeting is a very big meeting that happens once a year in June, and really, it is a national – actually, international – meeting where the biggest breakthroughs in cancer therapy are really presented and discussed. 

So, within the field of gynecologic cancer and specifically endometrial cancer, we really saw a couple breakthrough clinical trial results, if you will. The two specific trials that have hit the spotlight – and, it was presented at ASCO; they were also previously presented at the Society of Gynecologic Oncology annual meeting in March of 2023. These two trials – one of them is called GY018, and the other one is called RUBY, and these two trials specifically were geared at patients with endometrial cancer of either advanced stage, meaning stage III or IV at diagnosis, or patients who have recurrent endometrial cancer.  

And, these both trials were very large, multisite, international trials enrolling a huge number of patients. They were randomized controlled trials, meaning that they were specifically testing what we call a standard therapy, Taxol-carboplatin, versus a standard therapy plus a newer agent, and that newer agent falls in the realm of an immunotherapy drug. 

So, with this kind of novel approach, where we’re combining standardly used chemotherapy plus a newer immunotherapy drug, the question was if you did this combination, would patients have a better outcome? And, in fact, the groundbreaking news was that yes, patients did have a better outcome with this new combination of therapy, and this was shown in various forms of results. 

One of the primary outcomes is always something called survival, and with the GY018, they looked at progression-free survival as a primary outcome, and it did show that patients on this new combination did better with progression-free survival. And the difference was about median of about three months. Now, that may not sound like a whole lot. However, in the realm of cancer therapy, when you take a very large group of patients, that was a meaningful difference that was statistically significant. 

And furthermore, as we’re moving forward with our therapy drugs, we are moving into this era of targeted therapy, precision medicine, where we’re really trying to hone into more the specifics of the biology of each person’s cancer, and not treating everyone the same. 

What’s interesting with these two trials is when they looked at different subpopulations of patients with advanced or recurrent endometrial cancer, whether they had a type of endometrial cancer that was considered MSI-high, or a microsatellite instable type of cancer, which basically refers to a certain biology of these endometrial cancers, it has to deal with how the cells – the cancer cells – behave, how they’re able to not follow the rules and be able to replicate themselves. 

The patients who are MSI-high particularly had a really great response with this chemotherapy, so it was even beyond just a three-month difference. With that being said, even in patients who are what we call microsatellite-stable, who didn’t have this unique signature, they still saw a benefit with this novel combination, and to add to that, the nice thing about it is the toxicities were not bad. Even this new combination was very well-tolerated. 

It was not a high rate of severe toxicities or side effects, if you will, and that actually, the great majority of patients were able to stay on this therapy and really get through – complete the therapy course. 

So, there are some sort of nuanced differences between the two trials I mentioned, GY018 versus the RUBY. And some of those details are with regards to the even specific subtype of endometrial cancer, which we haven’t talked about yet, for example, uterine carcinosarcoma versus uterine serous carcinoma, uterine clear cell, uterine endometrioid – these are all specific subtypes of endometrial cancer. So there are some nuances where the RUBY trial was able to include patients with uterine carcinosarcoma, whereas the GY018 did not. 

But suffice it to say, now we have enough data that virtually all endometrial cancer patients with advanced stage, regardless of what histology, there is essentially a trial that can apply to you where it demonstrated this added benefit to doing this novel combination, and that was found with microsatellite-stable patients as well as microsatellite-instable in both randomized controlled trials that I mentioned. 

Katherine:

Such exciting news! That’s great! Well, beyond ASCO, Dr. Ko, are there other research or treatment advances that patients should know about?  

Dr. Ko:

Certainly. Like I mentioned, we’re really moving towards the realm of treating with a targeted therapy approach, and within endometrial cancer, the prior paradigm was much simpler, but really not in the space of target therapy. So, for example, what does that mean? 

So, as we’re realizing that there are very unique biologic signatures to different patients’ endometrial cancer – there could be, for example, some cancers that are particularly receptive to hormonal therapy, meaning their specific cancer, when we send it for detailed – we call it genomic or somatic testing, we can discover, oh, they have estrogen-receptor-positive, progesterone-receptor-positive, and so, those type of cancers may be very responsive to hormonal-based therapy, and in that space, we have a standard available drugs, but we also have clinical trials that are trying newer drugs. 

If, for example, the standard aromatase inhibitor or the standard progesterone agent may be helpful, but there are even more in that space that this point – CDK inhibitors that you can combine with these aromatase inhibitors or hormonal agents that have been around for longer that have shown a lot of promise, a lot of data in breast cancer. But now we’re realizing, wow, there could be some efficacy in endometrial cancer as well, so that’s just one example. 

And there’s other unique biologic gene signatures, again, kind of a good list now out there, that are being studied in various clinical trials, whether they’re PARP inhibitors, whether they’re drugs that target CCNE1, whether they’re drugs that target ARID1A, so there are actually many more that are available. So, they’re really expanding the opportunity for treatment for endometrial cancer patients. 

Katherine:

Well, you just mentioned clinical trials, and I think it’s a good topic to cover a little bit. Why is it important for patients to actually consider enrolling? What are the benefits for them? 

Dr. Ko:

Sure.

So, while we certainly have a good armamentarium of standard-of-care therapies already, and I should mention that does include our classic chemotherapy drugs like paclitaxel (Abraxane), carboplatin (Paraplatin), and even doxorubicin (Adriamycin), if you will, or doxorubicin Hcl (Doxil), there are the immunotherapy drugs now that have become standard of care as well, like pembrolizumab (Keytruda), but sometimes, despite using those best available drugs, the cancer unfortunately either continues to grow or you had a good response, but somehow it shows up again – the cancer shows up again – and so, then, we’re looking for additional opportunities, additional therapies. 

And so, some of the best opportunities are actually to consider these clinical trials. The way that clinical trials are designed is that they always are going  to provide you at least a backbone of a standard available therapy, so you’re never going to get less than what would be considered standard of care. 

But, what they’re doing is they’re usually partnering another drug – a more novel therapy – or they’re basically testing a more novel therapy that could be more targeted, that could potentially have better efficacy than what’s already available standardly. And so, the value of that is that you could have an opportunity to have a therapy that could work even better.  

When you’ve tried something already, unfortunately, the cancer has grown, there is still opportunity, and while you’re on a clinical trial, I think one of the huge benefits is it’s very regulated. You are monitored so closely because at the base of all of this is safety. There is never going to be a drug or therapy that’s going to be administered to a patient without ensuring that there’s absolute safety for that patient, and so, that’s a way that you really have opportunity to get more treatment that could really help your cancer condition and do it in a very, very safe, formal fashion. 

Katherine:

And ultimately help others as well, in the future.  

Dr. Ko:

Exactly, absolutely, because as you’re participating in this process – and, of course, it’s a voluntary process to participate on a clinical trial, so we so appreciate all the patients who, in the past, have participated and are willing to participate in the future, but allows us also to really gather a lot of information to really inform cancer treatment for all the patients coming down the road, and those could be anyone. They could be our neighbors, our friends, our own family members, and that could really be so helpful to everyone that’s going through this type of thing. 

Katherine:

Absolutely, yeah. I’d like to back up a bit and talk about what endometrial cancer is. It’s often referred to as uterine cancer. So, are they the same thing? Are these terms interchangeable? 

Dr. Ko:

Sure, it’s a great question. So, endometrial cancer refers to cancer that starts in what I call the lining of the uterine cavity. So, inside the uterus, there’s a uterine cavity, and there’s a tissue that coats that cavity, and that’s called the endometrium. So, endometrial cancer is basically when cancer cells start growing from that tissue. And, of course, since that exists in the uterus, of course, it’s considered uterine cancer, and we’re just being a little bit more specific when we say endometrial cancer. But, of course, endometrial cancer is the most common form of uterine cancer by far, so in some ways, it’s almost – it’s synonymous.  

Katherine:

How is endometrial cancer staged? 

Dr. Ko:

So, the most classic, rigorous way to stage endometrial cancer is through a surgical procedure. So, what that usually involves is it does include a hysterectomy, removing the uterus and the cervix, usually also includes removing the fallopian tubes and the ovaries. 

And, at the same time, the surgeon will do a very thorough assessment of the abdominal pelvic cavity, basically looking around all those areas to see if there’s any signs of visible disease, anything they can see that looks like it could be tumor deposits in the abdominal cavity. If anything is seen, those deposits will be removed and biopsied, so that’s part of the staging procedure. 

And additionally, it’s important to try to assess the lymph nodes, typically. So, there are lymph nodes in the pelvic area, and then, higher up along the aortic area, and so, there are different surgical techniques that we can use to basically test or sample some of those lymph nodes, be able to remove them, send them to the pathologist, look under the microscope to see if there are any microscopic cancer cells that have traveled to those lymph nodes. 

So, that is all part of a surgical procedure, and with all the information collected from those tissue samples that are removed from the body and sent to the pathologist, but the pathologist then reviews all of that under a microscope, and then can issue a very thorough report describing where the cancer cells are located, and by definition, where the cancer cells are located then defines what the stage is of the cancer. 

Katherine:

Can you give me an example? 

Dr. Ko:

Of course. So, for example, if the cancer cells are located only in the uterus, and they’re not found anywhere else, then that is a stage I. If the cancer cells have traveled to the cervix area specifically, this we call a cervical stroma, that becomes a stage II. If the cancer cells have, for example, traveled to the fallopian tubes, or the ovaries, or the lymph nodes, then that becomes a stage III, and there are sort of substages within those categories as well. 

Katherine:

But stage III would be the highest or most severe? 

Dr. Ko:

So, there’s stage III, and then there’s actually stage IV. So, if the cancer cells have traveled outside of the pelvis into the abdominal area, then we consider that a stage IV. 

Katherine:

And that would be considered advanced endometrial cancer? 

Dr. Ko:

Right. So, by definition, “advanced” typically refers to stage III or IV. 

Katherine:

I see, okay. Now that we understand more about the disease itself, I’d like to talk about the treatments that are currently available. You mentioned chemotherapy, but what else is available for people? 

Dr. Ko:

Absolutely. So, treatment for endometrial cancer is usually some combination of surgery, and then it may be followed by possibly chemotherapy, as well as radiation, and sometimes, it may be a combination of all three treatments, or sometimes, it’s a combination of one or two of those, depending on the exact stage, depending on the exact cell type, and some of the other factors. 

Katherine:

Are hormonal therapies used as well, and targeted therapies? 

Dr. Ko:

Yes. 

Katherine:

I know they are in other cancers. 

Dr. Ko:

Yes. And so, I think the question is where do those come into play? So, I would say the usual algorithm most commonly would be that surgery is done first, as the most common first step, and then, based on the information obtained from surgery and the pathology report that comes from that, then there’s usually some type of a recommendation about should there be a second stepped treatment, and that frequently can be chemotherapy/radiation.  

Now, the areas where targeted therapy – for example, immunotherapy – where does that come in? So, that now has come into the – I would call it the second stage. We’re combining it with the classic chemotherapy drugs – Taxol-carboplatin, for example. That’s one example where it could come into play. Another example could come into play where a patient had gone through classic Taxol/paclitaxel and carboplatin, then had cancer come back, and so, that could be another instance where that pembrolizumab or pembro with lenvatinib (Lenvima) combination can be used in the setting of recurrence. 

Now, we could also say, hey, if your cancer type has those hormonal receptors present or is some type of what we call endometrioid histology, and we think that hormonal therapy may be more effective in that case, then that could also be used in a setting where the cancer has kind of grown again, the cancer has grown back, or actually, there are certain situations where patients, for example, may not undergo a hysterectomy. 

And, there are unique cases and those situations where patients are still trying to preserve their fertility, and therefore not wanting to undergo a hysterectomy, or they’re unable to undergo surgery safely. And so, in some unique situations, we may also use hormonal therapy as the mechanism to treat their cancer, and whether that is by way of a pill, whether that is by way of a progesterone intrauterine device, IUD, that is placed into the uterus, we also have situations where we tailor the therapy to the condition of the patient. 

Katherine:

How are patients monitored for a recurrence, and are there approaches to help prevent a recurrence? 

Dr. Ko:

Sure, absolutely. Great question. It is important to continue monitoring patients, even after they’ve gone through treatment. So, I think of it as a multifaceted approach. Usually, it includes office visits, including a physical exam. It includes a thorough intake of all of their symptoms. 

It also includes – depending on the scenario – in some circumstances, regular imaging studies, such as a CT scan or MRI, and sometimes, we also do things like PET scans, and I think that does have to be tailored to the unique patient’s endometrial cancer, unique case, stage, histology, and we kind of tailor which tests we choose to do. The interval of monitoring can vary, so I would say generally speaking, it could be anywhere from three- to six-month visits, and with potentially added scans, as we talked about, and sometimes, we also do certain blood tests in certain cases where we may choose to follow a CA125 blood tumor marker. 

But, I would say that there are different, definitely variants to how we choose to monitor, and there are certain resources we tend to use, such as the NCCN guidelines that providers may reference, and sometimes may even share with the patients to explain why and how we choose to do the monitoring. 

Katherine:

When treating more advanced endometrial cancer disease in general, are the treatment options different than if you were treating somebody who had stage I or stage II, for instance? 

Dr. Ko:

Sure, great question. So, for some patients with, say, stage I, surgery alone is enough. 

For some other patients, subcategories of stage I, where we call them more high/intermediate-risk patients, they’re stage I, but there are a few features about their pathology that might make them slightly higher risk for recurrence – in those cases, we might consider a little bit of radiation after surgery, what we call adjuvant radiation or what we call radiation vaginal brachytherapy. Just three short treatments of a little bit of radiation to the top of the vagina has been shown to possibly decrease chance of recurrence in that area with very minimal side effects. 

So, that would be more commonly in line with stage I. There are some subtypes that can still be what we call high-risk, even in stage I/stage II uterine serous carcinoma, uterine carcinosarcoma. In those cases, we might also recommend chemotherapy along with some vaginal brachytherapy following their hysterectomy, so that’s the early stage. 

And then, with the advanced stage, yes. So, frequently, it’d be surgery first to secure the diagnosis, followed by some type of – it might be primarily chemotherapy, or it could be combination chemotherapy with radiation. And over time, I would say our paradigm for what we use for chemotherapy and radiation has changed a little bit. 

If you go back a couple decades, I think radiation was used a lot – whole pelvic radiation, even just without any chemotherapy. And then, we then had more data from research clinical trials, GOG-258 or PORTEC-3, that then had given us evidence that perhaps doing chemotherapy with some combination of radiation is going to be beneficial, or even moving towards primarily radiation could be a very good option in terms of long-term benefit/long-term survival. 

And, of course, that brings us to the present day, those two trials that I mentioned from ASCO, the GY018 and the RUBY, now bringing in the immunotherapy component to the chemotherapy, so there has definitely been an evolution to managing advanced stage. 

Katherine:

Yes. Dr. Ko, what goes into determining a treatment approach for an individual patient? Is there key testing that helps guide a patient’s prognosis and treatment options? 

Dr. Ko:

Absolutely. So, I think the key pieces of information come from several sources. First, we do take the whole patient into account, like baseline health, baseline function, meaning every day, how active are you? Are there limitations to your daily activities? Looking at baseline health conditions, what we call comorbidities. Are there other health conditions, like diabetes, heart conditions, lung condition, kidney conditions, that could really impact a patient’s overall health and wellbeing? That is always part of it, number one. 

Then, we look specific to the cancer details. So, from all the pathology information, biopsies, followed by a surgical staging procedure, what exact stage, what exact substage, and we might even look at other unique features. Was there cells that got into the lymph vessels, the lymph nodes? Are there other just features from a pathology standpoint that are important, like the – I talked about microsatellite status, microsatellite instable versus microsatellite stable. 

Those are all information we can gather from the tumor tissue itself. That then kind of tailors our therapy. And then, like I was saying, now we’re going into this molecular era where we can actually take that tumor tissue and even do more expanded testing on it. 

So, I think it’s worthwhile to talk to your provider and say, “Hey, would it be worthwhile to send my tumor out for expanded testing, whether it’s done at your institution, at a specialized lab, or whether it’s sent out to a company that does expanded testing?” Because then, they might be able to test for 500 different genetic signatures, a much more broad panel, but that might open the door for opportunities to say, “Hey, you actually do have a very unique signature, and maybe it is worth tailoring your therapy even further.” 

So, I think these are very important questions to have with your provider, and these pieces of information can help guide the prognosis. I think we’re always asking what does this mean long-term, and I think when we have all these individual pieces of information, we can then give guidance on that.  

Katherine:

Well, that leads me into my next question. I wanted to get your point of view on why is it important for patients to engage in their care and their treatment decisions? 

Dr. Ko:

Right. I think that it is so important. Medical treatments, I think, do work the best for the patient when the patient is truly an active participant, and what I mean by that is I think we can really understand the patient if there’s a conversation, there’s a mutual discussion, and I think every patient has unique circumstances, has unique goals, has…whether it’s just the daily whatever responsibilities, or just either health or non-health concerns that they have, we want to be able to find a treatment that fits the patient, and we realize that one treatment doesn’t fit all. 

And so, the more, I think, that there is this mutual discussion, mutual understanding, then there’s a mutual decision treatment plan that is made, and there’s the more ability to modify that plan when – if you realize, oh, maybe we can tailor it, maybe we try one thing, and maybe we realize we got to change a little bit.  

And, I think that with a cancer condition, it is a journey. It is not just a one-time thing. It really is a journey, and I think that the more a patient can participate throughout that journey, I think the better the outcomes for the patient, and honestly, the better the treatment course will be for everyone participating. 

Katherine:

Why should a patient consider finding an endometrial cancer specialist? What are the benefits? 

Dr. Ko:

So, I think naturally, an endometrial cancer specialist is a provider who spends more time thinking about the disease, reading about it, looking at what’s the newest research studies that are coming out, what are the available clinical trials here, locally, regionally, or nationally, what are other support services available for the patient in the space. 

And, of course, probably the folks that do the most surgeries gear towards endometrial cancer patients, and so, I think just working in that space naturally then brings more resources and more opportunity for the patient to kind of really know what’s out there, what is the newest, and I think that really benefits the patient. 

Katherine:

Thank you for sharing all this information. I’d like to close with your thoughts on the future of endometrial cancer care. Are you hopeful? 

Dr. Ko:

Yes. I think that I’m especially hopeful, especially within these last even few years, of where our field is going. I want to say I think there’s so much more that needs to be done.  

I don’t think we’re ready to close the books on endometrial cancer. I think this is just a wonderful opening of a chapter where we’re seeing many more therapies come about. I do think that something that is concerning is that we are seeing more cases of endometrial cancer being diagnosed – yeah, so it is absolutely true. There is very robust data that is collected by our CDC and cancer registry in the country, and it is showing that there is actually a rising incidence, that the number of endometrial cancer cases in this country is actually increasing over time, and it has – 

Katherine:

Why is that? 

Dr. Ko:

It’s a great question. 

Katherine:

Nobody knows – the data doesn’t include that information? 

Dr. Ko:

I think there’s definitely some information, there is definitely information out there. I think some of it – and this is not all of it – I think some of it is related to the increase in obesity and the increase in average weight over time, and this metabolic condition to some degree, I think, does stimulate potential risk for endometrial cancer. 

However, that is not the only reason, and what is concerning is that what we’re seeing is there’s a specific rise in subtypes of endometrial cancer in certain populations, particularly the Black and Hispanic patient populations, and we’re seeing a rise in the most aggressive types of endometrial cancer in those patient populations. I think there’s a lot of research going on right now in that to try to understand why. Is it just because we’re picking it up more? I don’t think that’s the bottom line. 

And, I think what we’re also realizing as we’re studying these various tumor types of endometrial cancer, they are driven by different biology. So, I think to some extent, the ones that are more maybe related to obesity or hormones and all may be slightly different – not completely separate, but that there is underlying different genetic basis for some of these cancers developing, and whether that’s a combination of underlying genes, environment, exposure, or all of the numerous factors, we just know it is happening, and so, it really is critical in my mind that the awareness and the focus and attention on endometrial cancers is really there, that we really think about it, that we share the information as much as possible, and that we can really then come to better – have more opportunity for treatments, be able to diagnose it sooner, be able to have more opportunities to treat it, and honestly, have better survival and outcomes for our patients. 

Katherine:

Dr. Ko, thank you so much for joining us today. You’ve given us so much information. 

Dr. Ko:

Thank you. It was my pleasure. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about endometrial cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for joining us. 

What Do You Need to Know About Emerging Endometrial Cancer Research?

What Do You Need to Know About Emerging Endometrial Cancer Research? from Patient Empowerment Network on Vimeo.

Endometrial cancer treatment and research is evolving quickly. Dr. Emily Ko provides an update on new and emerging approaches, explains how these therapies work to treat endometrial cancer, and shares tips for partnering with your team on key decisions.
 
Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.

Related Programs:

What Endometrial Cancer Patients Should Know About Clinical Trials

Endometrial Cancer Treatment Options for Patients to Consider

Endometrial Cancer Treatment Options for Patients to Consider

Emerging Endometrial Cancer Treatments _ Promising Data and Challenges

Emerging Endometrial Cancer Treatments | Promising Data and Challenges


Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients with endometrial cancer learn more about evolving research and treatments. We’re also going to discuss how patients can collaborate with their team on care decisions. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. 

At the end of the program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Emily Ko. Dr. Ko, welcome. Would you please introduce yourself? 

Dr. Ko:

Surely. Thank you so much. My name is Dr. Emily Ko, and I am a gynecologic oncologist. Currently, I’m an associate professor at the University of Pennsylvania, and as part of my daily work, I see patients, I provide surgical and medical treatments for gynecologic cancers, and I also am a researcher involved particularly in endometrial cancer. 

Katherine:

Thank you so much for taking the time out of your schedule to join us today. 

Dr. Ko:

Thank you. 

Katherine:

Well, let’s start by learning about the latest research news. Just this June, endometrial cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology meeting, or ASCO, in Chicago. Can you walk us through the highlights that patients should know about? 

Dr. Ko:

Sure. So, the ASCO meeting is a very big meeting that happens once a year in June, and really, it is a national – actually, international – meeting where the biggest breakthroughs in cancer therapy are really presented and discussed. 

So, within the field of gynecologic cancer and specifically endometrial cancer, we really saw a couple breakthrough clinical trial results, if you will. The two specific trials that have hit the spotlight – and, it was presented at ASCO; they were also previously presented at the Society of Gynecologic Oncology annual meeting in March of 2023. These two trials – one of them is called GY018, and the other one is called RUBY, and these two trials specifically were geared at patients with endometrial cancer of either advanced stage, meaning stage III or IV at diagnosis, or patients who have recurrent endometrial cancer.  

And, these both trials were very large, multisite, international trials enrolling a huge number of patients. They were randomized controlled trials, meaning that they were specifically testing what we call a standard therapy, Taxol-carboplatin, versus a standard therapy plus a newer agent, and that newer agent falls in the realm of an immunotherapy drug. 

So, with this kind of novel approach, where we’re combining standardly used chemotherapy plus a newer immunotherapy drug, the question was if you did this combination, would patients have a better outcome? And, in fact, the groundbreaking news was that yes, patients did have a better outcome with this new combination of therapy, and this was shown in various forms of results. 

One of the primary outcomes is always something called survival, and with the GY018, they looked at progression-free survival as a primary outcome, and it did show that patients on this new combination did better with progression-free survival. And the difference was about median of about three months. Now, that may not sound like a whole lot. However, in the realm of cancer therapy, when you take a very large group of patients, that was a meaningful difference that was statistically significant. 

And furthermore, as we’re moving forward with our therapy drugs, we are moving into this era of targeted therapy, precision medicine, where we’re really trying to hone into more the specifics of the biology of each person’s cancer, and not treating everyone the same. 

What’s interesting with these two trials is when they looked at different subpopulations of patients with advanced or recurrent endometrial cancer, whether they had a type of endometrial cancer that was considered MSI-high, or a microsatellite instable type of cancer, which basically refers to a certain biology of these endometrial cancers, it has to deal with how the cells – the cancer cells – behave, how they’re able to not follow the rules and be able to replicate themselves. 

The patients who are MSI-high particularly had a really great response with this chemotherapy, so it was even beyond just a three-month difference. With that being said, even in patients who are what we call microsatellite-stable, who didn’t have this unique signature, they still saw a benefit with this novel combination, and to add to that, the nice thing about it is the toxicities were not bad. Even this new combination was very well-tolerated. 

It was not a high rate of severe toxicities or side effects, if you will, and that actually, the great majority of patients were able to stay on this therapy and really get through – complete the therapy course. 

So, there are some sort of nuanced differences between the two trials I mentioned, GY018 versus the RUBY. And some of those details are with regards to the even specific subtype of endometrial cancer, which we haven’t talked about yet, for example, uterine carcinosarcoma versus uterine serous carcinoma, uterine clear cell, uterine endometrioid – these are all specific subtypes of endometrial cancer. So there are some nuances where the RUBY trial was able to include patients with uterine carcinosarcoma, whereas the GY018 did not. 

But suffice it to say, now we have enough data that virtually all endometrial cancer patients with advanced stage, regardless of what histology, there is essentially a trial that can apply to you where it demonstrated this added benefit to doing this novel combination, and that was found with microsatellite-stable patients as well as microsatellite-instable in both randomized controlled trials that I mentioned. 

Katherine:

Such exciting news! That’s great! Well, beyond ASCO, Dr. Ko, are there other research or treatment advances that patients should know about?  

Dr. Ko:

Certainly. Like I mentioned, we’re really moving towards the realm of treating with a targeted therapy approach, and within endometrial cancer, the prior paradigm was much simpler, but really not in the space of target therapy. So, for example, what does that mean? 

So, as we’re realizing that there are very unique biologic signatures to different patients’ endometrial cancer – there could be, for example, some cancers that are particularly receptive to hormonal therapy, meaning their specific cancer, when we send it for detailed – we call it genomic or somatic testing, we can discover, oh, they have estrogen-receptor-positive, progesterone-receptor-positive, and so, those type of cancers may be very responsive to hormonal-based therapy, and in that space, we have a standard available drugs, but we also have clinical trials that are trying newer drugs. 

If, for example, the standard aromatase inhibitor or the standard progesterone agent may be helpful, but there are even more in that space that this point – CDK inhibitors that you can combine with these aromatase inhibitors or hormonal agents that have been around for longer that have shown a lot of promise, a lot of data in breast cancer. But now we’re realizing, wow, there could be some efficacy in endometrial cancer as well, so that’s just one example. 

And there’s other unique biologic gene signatures, again, kind of a good list now out there, that are being studied in various clinical trials, whether they’re PARP inhibitors, whether they’re drugs that target CCNE1, whether they’re drugs that target ARID1A, so there are actually many more that are available. So, they’re really expanding the opportunity for treatment for endometrial cancer patients. 

Katherine:

Well, you just mentioned clinical trials, and I think it’s a good topic to cover a little bit. Why is it important for patients to actually consider enrolling? What are the benefits for them? 

Dr. Ko:

Sure.

So, while we certainly have a good armamentarium of standard-of-care therapies already, and I should mention that does include our classic chemotherapy drugs like paclitaxel (Abraxane), carboplatin (Paraplatin), and even doxorubicin (Adriamycin), if you will, or doxorubicin Hcl (Doxil), there are the immunotherapy drugs now that have become standard of care as well, like pembrolizumab (Keytruda), but sometimes, despite using those best available drugs, the cancer unfortunately either continues to grow or you had a good response, but somehow it shows up again – the cancer shows up again – and so, then, we’re looking for additional opportunities, additional therapies. 

And so, some of the best opportunities are actually to consider these clinical trials. The way that clinical trials are designed is that they always are going  to provide you at least a backbone of a standard available therapy, so you’re never going to get less than what would be considered standard of care. 

But, what they’re doing is they’re usually partnering another drug – a more novel therapy – or they’re basically testing a more novel therapy that could be more targeted, that could potentially have better efficacy than what’s already available standardly. And so, the value of that is that you could have an opportunity to have a therapy that could work even better.  

When you’ve tried something already, unfortunately, the cancer has grown, there is still opportunity, and while you’re on a clinical trial, I think one of the huge benefits is it’s very regulated. You are monitored so closely because at the base of all of this is safety. There is never going to be a drug or therapy that’s going to be administered to a patient without ensuring that there’s absolute safety for that patient, and so, that’s a way that you really have opportunity to get more treatment that could really help your cancer condition and do it in a very, very safe, formal fashion. 

Katherine:

And ultimately help others as well, in the future.  

Dr. Ko:

Exactly, absolutely, because as you’re participating in this process – and, of course, it’s a voluntary process to participate on a clinical trial, so we so appreciate all the patients who, in the past, have participated and are willing to participate in the future, but allows us also to really gather a lot of information to really inform cancer treatment for all the patients coming down the road, and those could be anyone. They could be our neighbors, our friends, our own family members, and that could really be so helpful to everyone that’s going through this type of thing. 

Katherine:

Absolutely, yeah. I’d like to back up a bit and talk about what endometrial cancer is. It’s often referred to as uterine cancer. So, are they the same thing? Are these terms interchangeable? 

Dr. Ko:

Sure, it’s a great question. So, endometrial cancer refers to cancer that starts in what I call the lining of the uterine cavity. So, inside the uterus, there’s a uterine cavity, and there’s a tissue that coats that cavity, and that’s called the endometrium. So, endometrial cancer is basically when cancer cells start growing from that tissue. And, of course, since that exists in the uterus, of course, it’s considered uterine cancer, and we’re just being a little bit more specific when we say endometrial cancer. But, of course, endometrial cancer is the most common form of uterine cancer by far, so in some ways, it’s almost – it’s synonymous.  

Katherine:

How is endometrial cancer staged? 

Dr. Ko:

So, the most classic, rigorous way to stage endometrial cancer is through a surgical procedure. So, what that usually involves is it does include a hysterectomy, removing the uterus and the cervix, usually also includes removing the fallopian tubes and the ovaries. 

And, at the same time, the surgeon will do a very thorough assessment of the abdominal pelvic cavity, basically looking around all those areas to see if there’s any signs of visible disease, anything they can see that looks like it could be tumor deposits in the abdominal cavity. If anything is seen, those deposits will be removed and biopsied, so that’s part of the staging procedure. 

And additionally, it’s important to try to assess the lymph nodes, typically. So, there are lymph nodes in the pelvic area, and then, higher up along the aortic area, and so, there are different surgical techniques that we can use to basically test or sample some of those lymph nodes, be able to remove them, send them to the pathologist, look under the microscope to see if there are any microscopic cancer cells that have traveled to those lymph nodes. 

So, that is all part of a surgical procedure, and with all the information collected from those tissue samples that are removed from the body and sent to the pathologist, but the pathologist then reviews all of that under a microscope, and then can issue a very thorough report describing where the cancer cells are located, and by definition, where the cancer cells are located then defines what the stage is of the cancer. 

Katherine:

Can you give me an example? 

Dr. Ko:

Of course. So, for example, if the cancer cells are located only in the uterus, and they’re not found anywhere else, then that is a stage I. If the cancer cells have traveled to the cervix area specifically, this we call a cervical stroma, that becomes a stage II. If the cancer cells have, for example, traveled to the fallopian tubes, or the ovaries, or the lymph nodes, then that becomes a stage III, and there are sort of substages within those categories as well. 

Katherine:

But stage III would be the highest or most severe? 

Dr. Ko:

So, there’s stage III, and then there’s actually stage IV. So, if the cancer cells have traveled outside of the pelvis into the abdominal area, then we consider that a stage IV. 

Katherine:

And that would be considered advanced endometrial cancer? 

Dr. Ko:

Right. So, by definition, “advanced” typically refers to stage III or IV. 

Katherine:

I see, okay. Now that we understand more about the disease itself, I’d like to talk about the treatments that are currently available. You mentioned chemotherapy, but what else is available for people? 

Dr. Ko:

Absolutely. So, treatment for endometrial cancer is usually some combination of surgery, and then it may be followed by possibly chemotherapy, as well as radiation, and sometimes, it may be a combination of all three treatments, or sometimes, it’s a combination of one or two of those, depending on the exact stage, depending on the exact cell type, and some of the other factors. 

Katherine:

Are hormonal therapies used as well, and targeted therapies? 

Dr. Ko:

Yes. 

Katherine:

I know they are in other cancers. 

Dr. Ko:

Yes. And so, I think the question is where do those come into play? So, I would say the usual algorithm most commonly would be that surgery is done first, as the most common first step, and then, based on the information obtained from surgery and the pathology report that comes from that, then there’s usually some type of a recommendation about should there be a second stepped treatment, and that frequently can be chemotherapy/radiation.  

Now, the areas where targeted therapy – for example, immunotherapy – where does that come in? So, that now has come into the – I would call it the second stage. We’re combining it with the classic chemotherapy drugs – Taxol-carboplatin, for example. That’s one example where it could come into play. Another example could come into play where a patient had gone through classic Taxol/paclitaxel and carboplatin, then had cancer come back, and so, that could be another instance where that pembrolizumab or pembro with lenvatinib (Lenvima) combination can be used in the setting of recurrence. 

Now, we could also say, hey, if your cancer type has those hormonal receptors present or is some type of what we call endometrioid histology, and we think that hormonal therapy may be more effective in that case, then that could also be used in a setting where the cancer has kind of grown again, the cancer has grown back, or actually, there are certain situations where patients, for example, may not undergo a hysterectomy. 

And, there are unique cases and those situations where patients are still trying to preserve their fertility, and therefore not wanting to undergo a hysterectomy, or they’re unable to undergo surgery safely. And so, in some unique situations, we may also use hormonal therapy as the mechanism to treat their cancer, and whether that is by way of a pill, whether that is by way of a progesterone intrauterine device, IUD, that is placed into the uterus, we also have situations where we tailor the therapy to the condition of the patient. 

Katherine:

How are patients monitored for a recurrence, and are there approaches to help prevent a recurrence? 

Dr. Ko:

Sure, absolutely. Great question. It is important to continue monitoring patients, even after they’ve gone through treatment. So, I think of it as a multifaceted approach. Usually, it includes office visits, including a physical exam. It includes a thorough intake of all of their symptoms. 

It also includes – depending on the scenario – in some circumstances, regular imaging studies, such as a CT scan or MRI, and sometimes, we also do things like PET scans, and I think that does have to be tailored to the unique patient’s endometrial cancer, unique case, stage, histology, and we kind of tailor which tests we choose to do. The interval of monitoring can vary, so I would say generally speaking, it could be anywhere from three- to six-month visits, and with potentially added scans, as we talked about, and sometimes, we also do certain blood tests in certain cases where we may choose to follow a CA125 blood tumor marker. 

But, I would say that there are different, definitely variants to how we choose to monitor, and there are certain resources we tend to use, such as the NCCN guidelines that providers may reference, and sometimes may even share with the patients to explain why and how we choose to do the monitoring. 

Katherine:

When treating more advanced endometrial cancer disease in general, are the treatment options different than if you were treating somebody who had stage I or stage II, for instance? 

Dr. Ko:

Sure, great question. So, for some patients with, say, stage I, surgery alone is enough. 

For some other patients, subcategories of stage I, where we call them more high/intermediate-risk patients, they’re stage I, but there are a few features about their pathology that might make them slightly higher risk for recurrence – in those cases, we might consider a little bit of radiation after surgery, what we call adjuvant radiation or what we call radiation vaginal brachytherapy. Just three short treatments of a little bit of radiation to the top of the vagina has been shown to possibly decrease chance of recurrence in that area with very minimal side effects. 

So, that would be more commonly in line with stage I. There are some subtypes that can still be what we call high-risk, even in stage I/stage II uterine serous carcinoma, uterine carcinosarcoma. In those cases, we might also recommend chemotherapy along with some vaginal brachytherapy following their hysterectomy, so that’s the early stage. 

And then, with the advanced stage, yes. So, frequently, it’d be surgery first to secure the diagnosis, followed by some type of – it might be primarily chemotherapy, or it could be combination chemotherapy with radiation. And over time, I would say our paradigm for what we use for chemotherapy and radiation has changed a little bit. 

If you go back a couple decades, I think radiation was used a lot – whole pelvic radiation, even just without any chemotherapy. And then, we then had more data from research clinical trials, GOG-258 or PORTEC-3, that then had given us evidence that perhaps doing chemotherapy with some combination of radiation is going to be beneficial, or even moving towards primarily radiation could be a very good option in terms of long-term benefit/long-term survival. 

And, of course, that brings us to the present day, those two trials that I mentioned from ASCO, the GY018 and the RUBY, now bringing in the immunotherapy component to the chemotherapy, so there has definitely been an evolution to managing advanced stage. 

Katherine:

Yes. Dr. Ko, what goes into determining a treatment approach for an individual patient? Is there key testing that helps guide a patient’s prognosis and treatment options? 

Dr. Ko:

Absolutely. So, I think the key pieces of information come from several sources. First, we do take the whole patient into account, like baseline health, baseline function, meaning every day, how active are you? Are there limitations to your daily activities? Looking at baseline health conditions, what we call comorbidities. Are there other health conditions, like diabetes, heart conditions, lung condition, kidney conditions, that could really impact a patient’s overall health and wellbeing? That is always part of it, number one. 

Then, we look specific to the cancer details. So, from all the pathology information, biopsies, followed by a surgical staging procedure, what exact stage, what exact substage, and we might even look at other unique features. Was there cells that got into the lymph vessels, the lymph nodes? Are there other just features from a pathology standpoint that are important, like the – I talked about microsatellite status, microsatellite instable versus microsatellite stable. 

Those are all information we can gather from the tumor tissue itself. That then kind of tailors our therapy. And then, like I was saying, now we’re going into this molecular era where we can actually take that tumor tissue and even do more expanded testing on it. 

So, I think it’s worthwhile to talk to your provider and say, “Hey, would it be worthwhile to send my tumor out for expanded testing, whether it’s done at your institution, at a specialized lab, or whether it’s sent out to a company that does expanded testing?” Because then, they might be able to test for 500 different genetic signatures, a much more broad panel, but that might open the door for opportunities to say, “Hey, you actually do have a very unique signature, and maybe it is worth tailoring your therapy even further.” 

So, I think these are very important questions to have with your provider, and these pieces of information can help guide the prognosis. I think we’re always asking what does this mean long-term, and I think when we have all these individual pieces of information, we can then give guidance on that.  

Katherine:

Well, that leads me into my next question. I wanted to get your point of view on why is it important for patients to engage in their care and their treatment decisions? 

Dr. Ko:

Right. I think that it is so important. Medical treatments, I think, do work the best for the patient when the patient is truly an active participant, and what I mean by that is I think we can really understand the patient if there’s a conversation, there’s a mutual discussion, and I think every patient has unique circumstances, has unique goals, has…whether it’s just the daily whatever responsibilities, or just either health or non-health concerns that they have, we want to be able to find a treatment that fits the patient, and we realize that one treatment doesn’t fit all. 

And so, the more, I think, that there is this mutual discussion, mutual understanding, then there’s a mutual decision treatment plan that is made, and there’s the more ability to modify that plan when – if you realize, oh, maybe we can tailor it, maybe we try one thing, and maybe we realize we got to change a little bit.  

And, I think that with a cancer condition, it is a journey. It is not just a one-time thing. It really is a journey, and I think that the more a patient can participate throughout that journey, I think the better the outcomes for the patient, and honestly, the better the treatment course will be for everyone participating. 

Katherine:

Why should a patient consider finding an endometrial cancer specialist? What are the benefits? 

Dr. Ko:

So, I think naturally, an endometrial cancer specialist is a provider who spends more time thinking about the disease, reading about it, looking at what’s the newest research studies that are coming out, what are the available clinical trials here, locally, regionally, or nationally, what are other support services available for the patient in the space. 

And, of course, probably the folks that do the most surgeries gear towards endometrial cancer patients, and so, I think just working in that space naturally then brings more resources and more opportunity for the patient to kind of really know what’s out there, what is the newest, and I think that really benefits the patient. 

Katherine:

Thank you for sharing all this information. I’d like to close with your thoughts on the future of endometrial cancer care. Are you hopeful? 

Dr. Ko:

Yes. I think that I’m especially hopeful, especially within these last even few years, of where our field is going. I want to say I think there’s so much more that needs to be done.  

I don’t think we’re ready to close the books on endometrial cancer. I think this is just a wonderful opening of a chapter where we’re seeing many more therapies come about. I do think that something that is concerning is that we are seeing more cases of endometrial cancer being diagnosed – yeah, so it is absolutely true. There is very robust data that is collected by our CDC and cancer registry in the country, and it is showing that there is actually a rising incidence, that the number of endometrial cancer cases in this country is actually increasing over time, and it has – 

Katherine:

Why is that? 

Dr. Ko:

It’s a great question. 

Katherine:

Nobody knows – the data doesn’t include that information? 

Dr. Ko:

I think there’s definitely some information, there is definitely information out there. I think some of it – and this is not all of it – I think some of it is related to the increase in obesity and the increase in average weight over time, and this metabolic condition to some degree, I think, does stimulate potential risk for endometrial cancer. 

However, that is not the only reason, and what is concerning is that what we’re seeing is there’s a specific rise in subtypes of endometrial cancer in certain populations, particularly the Black and Hispanic patient populations, and we’re seeing a rise in the most aggressive types of endometrial cancer in those patient populations. I think there’s a lot of research going on right now in that to try to understand why. Is it just because we’re picking it up more? I don’t think that’s the bottom line. 

And, I think what we’re also realizing as we’re studying these various tumor types of endometrial cancer, they are driven by different biology. So, I think to some extent, the ones that are more maybe related to obesity or hormones and all may be slightly different – not completely separate, but that there is underlying different genetic basis for some of these cancers developing, and whether that’s a combination of underlying genes, environment, exposure, or all of the numerous factors, we just know it is happening, and so, it really is critical in my mind that the awareness and the focus and attention on endometrial cancers is really there, that we really think about it, that we share the information as much as possible, and that we can really then come to better – have more opportunity for treatments, be able to diagnose it sooner, be able to have more opportunities to treat it, and honestly, have better survival and outcomes for our patients. 

Katherine:

Dr. Ko, thank you so much for joining us today. You’ve given us so much information. 

Dr. Ko:

Thank you. It was my pleasure. 

Katherine:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about endometrial cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for joining us. 

Updates in Prostate Cancer Treatment and Research | What You Need to Know

Updates in Prostate Cancer Treatment and Research | What You Need to Know from Patient Empowerment Network on Vimeo.

With research evolving quickly, it’s more important than ever that people with prostate cancer take an active role in their care. Dr. Channing Paller shares an update on recent prostate care treatment advances, discusses essential testing–including genetic testing–and provides advice for self-advocacy.

Channing Paller, MD is the Director of Prostate Cancer Clinical Research at Johns Hopkins Medicine. Learn more about this Dr. Paller.

Download Resource Guide

See More From INSIST! Prostate Cancer

Related Resources

Are We Getting Closer to Precision Oncology for Prostate Cancer

Are We Getting Closer to Precision Oncology for Prostate Cancer?

How Do Biomarker Test Results Impact a Prostate Cancer Patient’s Prognosis

How Do Biomarker Test Results Impact a Prostate Cancer Patient’s Prognosis?

What Questions Should Prostate Cancer Patients Ask About Testing and Test Results

What Questions Should Prostate Cancer Patients Ask About Testing and Test Results?


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell. Your host. Today’s program focuses on helping patients with advanced prostate cancer insist on better care. We’re going to discuss the latest research, current treatments, and how patients can collaborate with their healthcare team on key decisions.

Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar.

At the end of this program, you’ll receive another link to a program survey. Please take a moment to provide feedback about your experience today, in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.

Well, let’s meet our guest today. Joining me is Dr. Channing Paller. Dr. Paller, welcome. Would you please introduce yourself?

Dr. Paller:

Thank you, Katherine. I’m delighted to be here today. My name is Channing Paller. I’m Associate Professor of Oncology at Johns Hopkins and the director of Prostate Cancer Clinical Research.

Katherine:

Thank you so much for taking the time to join us today.

Dr. Paller:

Thank you for having me.

Katherine:

Dr. Paller, in June, prostate cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology, or ASCO meeting, in Chicago. Would you walk us through the highlights from that meeting that patients should know about?

Dr. Paller:

Absolutely. We’ve had a exciting time for prostate cancer in June. So, I’d say, the first thing I would bring up is, the PEACE-1 trial was discussed again, and more data came out from that trial. That trial originally supported what we found, the STAMPEDE trial, to say, yes, we should add abiraterone to androgen deprivation therapy and chemotherapy in helping de novo metastatic patients live longer and do better overall. And it also, this time around, showed us that combining abiraterone (Zytiga) with radiation, plus or minus chemo, had patients do better. So, they had a longer progression-free survival, or metastasis-free survival.

And also, the neat thing was, patients had fewer local symptoms in the long run. So, it prevented catheters being needed later, prevented blockages. It prevented local side effects from their cancer, which was really terrific to know, because that helps with patients’ quality of life.

That was one of the main, personally. Go ahead.

Katherine:

Yeah, I was just going to ask, anything else?

Dr. Paller:

Yes. So, the second big headline, which is one of my dear loves, is all of the PARP inhibitor data. So, there were a couple trials presented, and this month has been terrific in terms of, there have been two drug approvals. So, let me talk through a couple of those.

So, one of the big ones that was presented at ASCO was looking at talazoparib (Talzenna) and enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer, and it showed that the combination of those two drugs helped patients do better than enzalutamide alone, in that setting. What was also interesting is a subset of patients with DNA repair mutations did even better.

June 20th, the FDA approved that combination for patients with metastatic castration-resistant prostate cancer with DNA repair mutations.

We also had a drug approval for abiraterone (Zytiga) and olaparib (Lynparza) in the same space of metastatic castration-resistant prostate cancer for patients with BRCA mutations. That was a more narrow approval, but it was still very important.

And what’s exciting here is, we’re really learning more about targeted therapy, precision medicine, for our prostate cancer patients. When I started treating prostate cancer patients back in 2005, the main drug approved was chemotherapy, docetaxel (Taxotere), and hormone deprivation therapy. And in the last almost 20 years, or 18 years, we’ve had 10 drug approvals, and we’re really starting to have multiple drugs approved based on people’s genetics.

Katherine:

That’s such promising news. I mentioned at the top of the program that our focus for this webinar is advanced prostate cancer. So, I’d like you to define that. What is advanced prostate cancer? And is any of the research you mentioned focused on this stage of disease?

Dr. Paller:

Well, advanced prostate cancer includes any prostate cancer that was extended outside the prostate, really, that’s spread to the nodes, even to the lymph nodes, to the liver, to the lungs, to the bones. And so, we have a lot of new findings, looking at this space, and that was a lot of what they showed at the ASCO conference.

The other thing we’re learning is that we really want to get genetic testing on everybody. And so, in addition to your regular, “How do you feel?” “What do your labs show?” “What is your PSA doing?”

We also want to get imaging, right? So, we want to look at imaging, in terms of, what did your CT and bone scan show? And nowadays, we’re moving into PSMA, or prostate-specific membrane antigen, PET scans.

And so, that’s the new main way people look at where their prostate cancer has gone, and help them decide, what is the best treatment for me? Is it to get surgery locally, or has it advanced now, and I really need to do hormone therapy and radiation, or some other combination of systemic therapy, meaning more hormones, or more chemotherapy, with targeted therapies such as radiation?

Katherine:

Beyond ASCO, Dr. Paller, are there other research or treatment advances that patients should know about? Anything other than what you’ve mentioned already?

Dr. Paller:

Oh, yes. So, the other headline that I was really excited about at ASCO is watching medicine adopt the world of artificial intelligence. There was a great abstract, looking at how we can use artificial intelligence to look up pathology slides.

So, in the past, we would always want to go to a top academic center to have your pathology reviewed by a top expert and make sure we were treating the right cancer, and make sure we really understand your risk. What we’re finding is, we can create biomarkers, and we’re understanding not just genetic, genomic biomarkers, but also pathology biomarkers, and age, and PSA, and risk, and comorbidities, and we can combine them all together and use AI to help us better stratify patients.

And so, although it’s early, I think this is going to be an explosion in terms of helping us better define risk for patients in advanced prostate cancer, and help them figure out, do they need intensification of treatment, or can we de-intensify treatment? Can we not cause as much toxicity, and they’ll do just as well? And so, I was really excited to see that data as well.

Katherine:

How can patients stay up to date on evolving research?

Dr. Paller:

There are many ways to stay up to date. There are nice summaries at ASCO. There are nice summaries through the Prostate Cancer Foundation. There are good summaries at each of the institutions with whom you work.

One of my favorite ways to stay up to date on precision medicine is one of these registries that I am co-leading, which is called the PROMISE registry. This is a wonderful opportunity which was conceived in the pandemic.

And so, it’s pandemic friendly, and that is called the PROMISE registry. And what you can do is go to prostatecancerpromise.org and sign up if you have prostate cancer. And you say, “Hey, I have prostate cancer. This is my address. Please ship me a kit where I can do saliva testing of my genes.” And once you get your tests sent in, they’ll send you a kit, you send it back, you’ll get an email, and you can go over your results with a genetic counselor.

And then, once you get enrolled in this program, it is really just a free information source. And so, you can learn more about the clinical trials around the country for patients with different mutations. And so, I love that as, whether or not you have a mutation and you’re going to follow with us for 20 years, because we’re going to offer you opportunities and let you be the first to know about new drug approvals, you can still hear about all of the new research.

And I think that’s a wonderful, free resource that we’ve done for our patients to help them understand more about what’s out there. Another opportunity to learn more about prostate cancer is the prostate cancer clinical trial consortium. They have a nice website looking at germline genetics, looking at diversity, looking about clinical trial design. And so, there’s lots of different places to learn more about prostate cancer.

Katherine:                  

Dr. Paller, what about clinical trials? Why should patients consider enrolling, and what are the benefits for them?

Dr. Paller:                   

I like to tell my patients that once you have metastatic or advanced prostate cancer, we’re not doing placebo on you. If we’re doing placebo, it’s the standard of care plus a new drug, and we want to know if the new drug in combination with the old drug is better than the old drug alone.

And so, I find those patients heroes, in one sense, for the future, right? They’re helping to approve the new drugs of the future, and I also find, oftentimes, those are the patients that do best, because they’re getting to try all of the new drugs of the future before they’re approved. And so, I will have patients that are, I call them chronic trialists because they’ll go through all my new drugs before they’re even approved.

And I love it, and they love it, because they do better than the average, because they’re exploring all of the new therapies. And so, I find those patients heroes, and I really appreciate their efforts. I would say, the most important thing about clinical trials is learning about them, right? And being able to ask the questions. “Well, what phase is that trial?” So, Phase I is really testing safety, and finding the right dose for patients. And so, that’s usually a small number of patients, and looking exactly at, does this work? Do we have a biomarker to follow? What’s the best way to use this new drug?

Phase II starts to look at efficacy, as well as looking at side effects. And so, with Phase II, we really look at, what is the effect? Is it better than what we expected? Does it help these patients – is it better than some of the other drugs?

And then, Phase III are usually large trials that are looking at FDA approval. They’re looking for registration with the FDA, getting approval, and being the new standard of care that’s paid for by insurance companies.

Katherine:                  

I’d like to back up a bit and talk about the treatments that are currently available. Let’s start with surgery. What role does that play in treating advanced disease?

Dr. Paller:                   

Surgery is one of the key tools that we use when we’re trying to cure prostate cancer when it’s localized, or just starting to spread. But if it’s too advanced, meaning, spreading to the lymph nodes, we usually don’t recommend surgery. So, surgery is usually used for curative intents, although there is a trial ongoing now, looking at the same question of, is adding surgery to systemic therapy helpful in terms of long-term cure rate, in terms of decreased side effects later, and local symptoms later?

And so, we are asking that question. That is one of the ongoing clinical trials that we’re looking at right now, as a group.

Surgery is terrific. Radiation is terrific. Really working with your team to understand for you, what are the side effects that you would undergo? What are the risks and benefits of each modality that you would like to, or that you’re willing to tolerate? And so, I think the differences between surgery and radiation, for curing patients, are really something that you need to discuss with your provider. The risk of erectile dysfunction, the risk of the local symptoms from the radiation, the risk of having bleeding from your bladder, the risk of bowel problems. Those are all things that that you – urinary incontinence – that you need to discuss with your physician.

Katherine:                  

What are other options that are available now, for patients?

Dr. Paller:                   

For curative intent, the main two treatment options are surgery, radiation. Many people for very localized disease are trying other therapies, such as cryotherapy, and more focal therapies. But really, for curative, the standard is surgery or radiation. And as it gets more advanced, circling back to advanced prostate cancer, we are learning that combination therapy is better. So, adding pills like abiraterone, adding systemic therapies, help patients do better.

So, there’s a big, long list of therapies upfront that we use for metastatic hormone-sensitive prostate cancer. There’s abiraterone, there is apalutamide (Erleada), there’s enzalutamide, and now, darolutamide (Nubeqa).

And in fact, in fit patients that can tolerate chemotherapy for metastatic high-volume prostate cancer patients, we always recommend triple therapy, either with abiraterone, docetaxel, and ADT, or with darolutamide, docetaxel, and ADT, and these patients really seem to do better for longer. The other thing I would add is the PEACE-1 trial, which looked at abiraterone and docetaxel, found that patients would do best by adding growth factor support. And so, that is recommended.

The other thing I want to point out to patients is, I know we’re all eager to get started when we find out we have a diagnosis of metastatic prostate cancer, but sometimes, these therapies are quite tough on the system when you have a lot of cancer in your body, and my recommendation to everybody is, one thing at a time.

So, start the hormone therapy and wait at least 30 days, and in fact, in the PEACE-1 trial, they waited 45 days, right? That allows the testosterone levels to fall, it allows you to adjust to the side effects of hormone deprivation therapy, and it allows your body to be ready for the next line of therapy. And you can add the ADT to second line, such as abiraterone or daro during that time, but not adding the chemo all at once, that really makes a difference.

I find, unfortunately, when patients and their providers don’t follow those strict criteria, as they did in the trial, meaning they start chemo and abiraterone and ADT on day one, the levels of chemotherapy get higher in the bloodstream because testosterone regulates that, and we’ve published on that before. And they end up with terrible side effects from the chemotherapy, such as neutropenic fever, which means you end up in the hospital with a bloodstream infection and a fever, and more neuropathy, meaning numbness and tingling in your hands and feet.

And so, I really caution people to spread those therapies out over the first 90 days, and you’ll do better in terms of side effects, and just as well in terms of overall survival.

Katherine:

Where does hormonal therapy fit into the treatment options, and have there been any advances in hormonal therapy?

Dr. Paller:     

Yes. So, hormonal therapy is the mainstay of how we take care of prostate cancer patients, whether we do this with surgical castration, which is not done very often anymore, or we do it with an LHRH agonist, or we do it with an LHRH antagonist. So, that means that we can do it with medicines that block the signaling, but that tells your body to produce testosterone in various ways. What’s really neat is we’ve made advances, that there are now oral options for some of these therapies.

In particular, there’s a new therapy called Orgovyx, or relugolix, that is an oral LHRH antagonist that locks testosterone and allows us to stop prostate cancer growth. In addition, there are a variety of LHRH agonists that can be given as subcutaneous shots. 

Katherine:                  

Dr. Paller, let’s talk about what goes into deciding on a treatment path. First, what testing helps you understand the patient’s individual disease?

Dr. Paller:                   

Great question.

When I meet a patient, we talked about a few variables. First is, how do they feel? Are they in pain? Are they losing weight? Are they fatigued all the time? Are they able to do things that they enjoy, or not? So, that’s the most important, in terms of, how do they feel, and what are their symptoms?

The next thing we looked at is, what are their labs, right? We look at PSA, but we also look at, is the prostate cancer affecting their organs? Is it affecting their red blood cells, their platelets, their white blood cells? And very importantly, it tells us, by looking at their alkaline phosphatase, if it’s in their bones or not. And we also can look at their labs to see, is it affecting their liver or not. Another thing we monitor is their creatinine or kidney function. Is there a blockage of their important organs down there because the prostate cancer has grown? So, the labs tell me a lot about their body function, and making sure their body is still functioning well.

After we do how they feel, and what their labs are, we also look at imaging. And then, the previous years, we’ve always looked at a standard nuclear medicine bone scan, and also, a CAT scan. And nowadays, we’re really moving towards PSMA, or prostate specific membrane antigen, to help us really identify, at a much more sensitive level, where prostate cancer cells are expressed.

And after we do those main three key things, we start to look at diagnostic tests. We look at different ways of assessing what are their genes. So, one of the first things we do is looking at germline genetic testing to see, what were the genes they were born with? And can those genes help us learn more about their cancer, and how it might progress? And also, how we might treat it better if they have certain genes like BRCA.

The other nice thing about genetic testing, or germline genetic testing, is looking at, if they do have a genetic mutation, or a pathologic variant like BRCA, we are always, always telling families that they should get cascade testing for their familyright? So, if they have a mutation, we recommend that their family members get tested to make sure that they’re not at risk for a cancer. And so, we have them meet with a genetic counselor.

So, in addition to what you’re born with, we also want to know what your cancer has developed, because cancer cells are growing quickly, and they can develop a mutation. And so, we also test the cancer, get genomic testing of the cancer, to look for mutations that we can target with our multiple drugs that we’ve approved to target cancers in certain mutations. So, you have something called MSII, we have immunotherapy for you. If you have DNA repair mutations, we have PARP inhibitors for you, or even carboplatin (Paraplatin) can be added to target patients with DNA repair mutations as well.

And so, there’s a whole variety of tests out there by a multitude of providers, that help us really better understand your cancer.

Katherine:                  

And the treatment options, by the sounds of it.

Dr. Paller:                   

And the treatment options. Yes, there is. There’s a whole variety of it. Yeah.

Katherine:                  

So, what is personalized medicine, Dr. Paller? And how is it achieved?

Dr. Paller:            

Personalized medicine means many things to many different people. I find the most important thing is not forgetting the patient. The patient needs to be their own advocate, and have an advocate there with them, right? Because maybe the best treatment is chemotherapy, hormone therapy, radiation, etc., etc., but maybe you’re 92, and you’ve lived a good life, and you have heart disease, and you might not die of your prostate cancer. And so, overtreating people is just as dangerous as undertreating people.

And so, precision medicine is a whole variety of things, of looking at the whole person, looking at their genes, looking at biomarkers their cancers produce, and looking at what comorbidities they have, right? If you have really bad diabetes, maybe you don’t want me to add steroids to your regimen. If you have a seizure disorder, maybe you don’t want me to add insulin. I wouldn’t, because there’s a seizure risk. If you have various problems, we just need to take those into account and find the best therapy for each individual.

Katherine:                  

I think you’ve covered this, in a sense, but I’m going to ask you the question anyway. Why is it important that patients have a role in making decisions about their care?

Dr. Paller:                   

It is essential that patients have a role in their care so that they are taking ownership and being part of the team, to care for themselves, not to put extra weight or work on the patient, but really, so that they know they’ve made the right choice for them.

Understanding a patient’s priorities are essential. Some patients may not want the side effects of hormone therapy, and they may say, “Hey, I have oligometastatic disease, meaning I just have one spot to my bones, and I’m 80 years old. And Dr. Paller told me that the sub analysis of this triple therapy, new trial, showed that, I’m over 75, I may not benefit as much. And you know what? I don’t want to have the side effects of hormone therapy. I don’t want to lose muscle mass. I don’t want to have hot flashes. I don’t want to have erectile dysfunction.”

“I want to enjoy my life, even if it’s slightly shorter, and it might not be slightly shorter.” And so, I find, having a partnership with a patient to really understand their priorities makes life worth living more, right? So, maybe a patient’s priority is finding time with their grandchildren. Maybe a patient’s priority is getting a PhD. Whatever their patient’s priority is, it is important that we put that to the context of their whole being and helping them really find the best therapy for them, to help them do as well as they can, as long as they can.

Katherine:                  

I think this this leads us very nicely into the next topic, and that’s self-advocacy. While the goal of this program is to help patients insist on better care, there may be factors that impact their access. What common obstacles do patients face?

Dr. Paller:                   

The main obstacle for patients is insurance. Unfortunately, I find that it’s frustrating to not be able to provide patients with oral hormonal therapy if they can’t afford it, because they don’t have insurance, and it’s too expensive. But there are other challenges that patients face, right? If they’re young and don’t have childcare, if they have trouble getting time off their work. But I think one of the major problems is economics, and can they get the same care, and can they advocate for themselves, right? So, another problem is, if you are in a community practice, you might not have access to the top diagnostic testing.

And it’s really important that you advocate for yourself and get a second opinion at an academic center where you can get the best testing and figure out the best path for yourself. And sometimes, if patients are at sites where they’re seeing a generalist, they’re not going to get access to that, because that’s not standard at that hospital.

Katherine:                  

Yeah. Well, what is the medical community doing to help improve access?

Dr. Paller:                   

We are working hard on reaching out into the community. One of the other hats I wear is, I’m Associate Program Director for the Johns Hopkins Clinical Research Network for oncology. And one of my jobs is to find communities that want to open trials at community sites.

These aren’t our super complicated phase I trials. These are often simple Phase II or Phase III trials that patients can participate in, and really get access to new biomarker tests, get access to new treatments, and really be connected to the centralized knowledge that is available at academic centers.

And I think all of ASCO is doing this, I think all the Prostate Cancer Consortium is doing that, I think the PCF is doing this, and we really are – and I even think the drug companies are reaching out and educating primary care doctors, urologists, radiation oncologist patients.

There are a lot of programs we now do that are direct to patient education, so that we’re not dependent on whether or not the doctor has time to explain these things. And so, programs like this are really wonderful at keeping the patients educated and able to advocate for themselves.

Katherine:                  

What diversity in clinical trials? Is that an emphasis for the research community?

Dr. Paller:                   

Absolutely. I think that’s an emphasis across the board in society today.

We are eager to learn more about how patients with different genetic profiles, with different ethnicities, with different socioeconomic backgrounds, are reacting differently to different therapies. If you’re African American, do you respond differently to [treatment] with one study we looked at? If you have a different diet, are you going to respond differently to immunotherapy? And really understanding different demographics is really important to us at this time.

Katherine:                  

Are there resources that patients can turn to that would help them gain better access to healthcare?

Dr. Paller:                   

There are programs that are available either through your local community, or another one that has a nice patient centered education program is NCCN, or the National Comprehensive Cancer Network. They have summaries of your tumor type across the board, and how to best treat it.

They also have a list of experts that helped make those guidelines, so that you could reach out to those centers and know the main centers that are treating your cancer.

Katherine:                  

That’s great advice. Thank you. If a patient is feeling like they aren’t getting the best care, though, what steps should they take to change that?

Dr. Paller:                   

That’s a good question. So, being a self-advocate takes energy, when oftentimes, you’re tired and overwhelmed at your cancer diagnosis. And so, my heart goes out to all of those patients. Really, finding a second opinion, and finding an academic center or a large program that has a prostate cancer focused program, is helpful.

Or whatever your tumor or issue is, going to a center that is a specialist in that, for a second opinion, is often helpful, and can work with your local physician to help get you the care that you need.

Katherine:                  

That’s great information, Dr. Paller. Thank you. As we wrap up, I’d like to get your closing thoughts. How do you feel about the future of prostate cancer care? Are you hopeful? Encouraged?

Dr. Paller:                   

I am so hopeful and encouraged. We are exploding in the number of drugs we have. We are exploding in the number of opportunities and precision medicine drugs that we’re having. This is a wonderful time where we’re combining our understanding of genetics, and biomarkers, and AI, and pathology, and imaging, and I am thrilled.

I think we’re really going to be able to understand which patients should get which drugs without having so much toxicity. And such a high failure rate here, or how do I know who will get the best treatment?

“We’re just going to try it and see.” I don’t want to have to say that in five years. I want to say, “I know this will work, and I can control your symptoms and your side effects.”

And so, I am so excited about the future. I think we’re just making huge strides every day now, and I think this will be a whole new world in the next five years.

Katherine:                  

Dr. Paller, thank you so much for joining us today.

Dr. Paller:                   

Thank you so much, Katherine.

Katherine:                  

And thank you to all of our collaborators.

If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about prostate cancer, and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. Thank you, Dr. Paller. Great information.

Are MPN Risks and Outcomes Impacted by Race or Ethnicity?

Are MPN Risks and Outcomes Impacted by Race or Ethnicity? from Patient Empowerment Network on Vimeo.

Are myeloproliferative neoplasm (MPN) risks and outcomes impacted by patient race or ethnicity? Expert Dr. Idoroenyi Amanam from City of Hope explains common MPN symptoms, potential risks and outcomes, and patient advice for optimal care.

[ACT]IVATION TIP:

“…if you have stroke, heart attack, blood clots, abnormal counts, please follow up with your doctor and ensure that you get referred to the appropriate specialist to help assist in managing your complications.”

Descargar Guía|Download Guide 

See More From [ACT]IVATED MPN

Related Resources:

Myeloproliferative Neoplasm Basics for Newly Diagnosed Patients

Myeloproliferative Neoplasm Basics for Newly Diagnosed Patients

What Does the Future of Myeloproliferative Neoplasm Care Look Like?

What Does the Future of Myeloproliferative Neoplasm Care Look Like?

MPN-Related Complications | Are BIPOC Patients at Higher Risk

MPN-Related Complications | Are BIPOC Patients at Higher Risk?

Transcript:

Lisa Hatfield:

Dr. Amanam, how does race impact clinical MPN outcomes or complications? And are certain populations more susceptible to getting MPNs?

Dr. Indoroenyi Amanam:

Yeah, it’s a great question. I think, because of the fact that symptoms are not as clearly related to MPNs as opposed to some other diseases. So the major presenting symptoms for MPNs are related to high blood pressure or some other vascular abnormality, including strokes or blood clots. It takes a little work to diagnose MPN patients, and half of them are asymptomatic. And if you actually look at diagnosis rates, they’re one to three cases per 100,000 per year. And so this is very rare, and I think that we don’t have enough data to really understand if some groups are at higher risk to develop MPNs than others.

We have looked at incidences of thrombotic events in patients who have MPNs, and we tried to see if there was a difference between racial groups, and we didn’t. We did see that if you’re younger, you do have a higher risk of thrombosis over time, but there was no difference for if you were white, Hispanic, or African American.

What we did find though, in a small single center study is that if you are non-white, there’s a higher risk of death over time. And I think we still need a lot of work to get a better understanding as why that’s the case. So far we don’t have a clear signal for that, but I do think, in the same…the story that we understand for healthcare in general, there are some differences in terms of access to care, the quality of care that’s delivered in, you can guess that possibly that’s one of the reasons why that that affects African Americans and Hispanics disproportionately in this setting as well.

So my activation tip for this question would be if you have stroke, heart attack, blood clots, abnormal counts, please follow up with your doctor and ensure that you get referred to the appropriate specialist to help assist in managing your complications. 


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CLL and BTK Inhibitor Treatment: What Are the Risk Factors?

CLL and BTK Inhibitor Treatment: What Are the Risk Factors? from Patient Empowerment Network on Vimeo.

What’s important for chronic lymphocytic leukemia (CLL) patients to know when considering BTK inhibitor treatment? Expert Dr. Ryan Jacobs explains some cardiac risk factors with BTK inhibitors and patients who might want to consider other treatment options. 

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

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Transcript:

Lisa Hatfield:

So this patient is asking, “For patients who may be eligible for BTK inhibitors, are there specific comorbidities that might contribute to adverse side effects?”

Dr. Ryan Jacobs:

Yeah, so we screen…all BTK inhibitors have some cardiac toxicity. They have been shown with the second-generation BTK inhibitors to have less cardiac toxicity than ibrutinib, specifically atrial fibrillation. So if you have atrial fibrillation, maybe that’s a reason why you might go on venetoclax first as opposed to a BTK inhibitor. But it’s not a contraindication to getting a BTK inhibitor if the atrial fibrillation is under good control. Other cardiac risk factors would include difficult to control hypertension at baseline, or heart failure. These are all things that might make us think twice about using a BTK inhibitor as our first therapy, because venetoclax has no cardiac toxicities.

The other thing to consider is BTK inhibitors all to a degree have, and I describe it to patients, like an aspirin-like effect on the platelets. They do interfere with the platelet binding, which so universally, patients will know to varying levels some easier bruising. And if patients are on, because of say, they’ve had a heart attack in the past and they’re on aspirin at baseline, or what would even be more concerning if they were on a drug like Plavix because they’ve had a stent placed, that would be something that would really concern me and would definitely push me more towards venetoclax (Venclexta), that again, doesn’t have those anti-platelet interactions. Also, patients who are on blood thinners because of a history of blood clot or atrial fibrillation, there is the potential increased risk for bleeding and bruising there as well.  None of these are absolute contraindications, they’re just all what goes into the blender, if you will, of putting lots of information in and coming up with the best treatment decision as personalized for the CLL patient. We’re blessed to have multiple options, but it does make it more of a challenge to find the “best” option. 


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Clinical Trials As a Prostate Cancer Treatment Option | What You Should Know

Clinical Trials as a Prostate Cancer Treatment Option | What You Should Know from Patient Empowerment Network on Vimeo.

Should you consider participating in a prostate cancer clinical trial? Dr. Sumit Subudhi explains the clinical trial process, addresses common trial patient concerns, and provides key advice for trial participation. Dr. Subudhi also shares an update on promising prostate cancer research.

Dr. Sumit Subudhi is an Associate Professor in the Department of Genitourinary Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

See More From Prostate Clinical Trials 201

Download Resource Guide

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Tools for Choosing the Right Prostate Cancer Treatment Approach


Transcript:

Katherine Banwell:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss prostate cancer research advances and the role of clinical trials and moving treatment developments forward. Before we meet our guest, let’s review a few important details.   

The reminder email you received about this program contains a link to a program resource guide. 

If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you will receive a link to a program survey. This will allow you to provide feedback about your experience today, and it will help us plan future webinars. 

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. 

Well, let’s meet our guest today. Joining me is Dr. Sumit Subudhi. Dr. Subudhi, thanks for being with us. Would you introduce yourself? 

Dr. Subudhi:

Hi. I’m Sumit Subudhi. I’m an associate professor in the GU Medical Oncology department at MD Anderson Cancer Center. And I exclusively treat patients with advanced prostate cancer. And I’ve been doing it for about a decade. 

Katherine:

Thank you. I’d like to begin with an update on prostate cancer research. Would you walk us through the newer classes of treatments that are showing promise? 

Dr. Subudhi:

Yeah, in clinical trials, there are classes of drugs known as androgen receptor degraders. And so, the androgen receptor is a protein that basically is the mouth of the prostate cancer. That’s how I like to describe it. And it actually allows testosterone, which is the food, to be eaten by the mouth, and it actually helps the cancer grow. 

And what these drugs do is they actually degrade or break down the mouth of the cancer. And, therefore, it starves the cancer to death, and that’s actually the concept. And they seem to be showing some exciting activity in clinical trials, especially in those patients who are resistant to the second-generation hormonal drug that you may have heard of already, such as enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). So, I think is something that we’re looking forward to seeing more data on. 

Another class of drugs are antibody drug conjugates or ADCs.  

And these are what I think of as heat-seeking missiles. So, one part of the drug actually recognizes the cancer, and the other part of the drug actually has a payload that sort of releases a bomb or sort of like chemotherapy-type agent right where the cancer’s located and kills the cancer in that way. And we’re seeing some great clinical activity in prostate cancer with this class of drugs. 

And then the final one is bispecifics, and in particular T-cell bispecifics. So, T cells are part of the immune system that actually help kill the cancer.  

And, unfortunately, prostate cancer, like some other cancers like pancreatic and glioblastoma, have few T cells inside it. And, therefore, a lot of the immunotherapies that many people have heard about, such as ipilimumab (Yervoy) and pembrolizumab (Keytruda), they’re not very responsive in patients with prostate cancer. And it’s because there’s few T cells in prostate cancer.  

What the T-cell bispecifics do is they actually have one part of the drug that actually recognizes the cancer and the other part that recognizes T cells. So, like a bulldozer, it brings T cells right into the prostate cancer and helps kill the cancer that way.  

Katherine:

Now there are some inhibitors as well. Is that correct? 

Dr. Subudhi:

Yeah. So, the immune checkpoint inhibitors have been around for a while. And, basically, in combination, they seem to be more effective in prostate cancer. But when given alone as monotherapy, they’re less effective. 

Katherine:

Are these treatments specifically for patients with advanced prostate cancer? 

Dr. Subudhi:

All of them are actually in trials in patients with advanced prostate cancer. And I define advanced prostate cancer as either having metastatic disease, meaning the cancer has spread to other parts of the body outside of the prostate.  

Examples include lymph node, the bone, the lung, the liver. But there are so few trials in patients with locally advanced prostate cancer. What I mean by that is they have high-grade prostate cancer, but it’s local, or it’s just in regional lymph nodes. And some of these classes of drugs are being evaluated in that setting as well. 

Katherine:

Let’s shift to talk about your research. What are you excited about right now? 

Dr. Subudhi:

So, my research focuses on immune checkpoint therapies, which are the inhibitors that you were referring to and understanding how to make them work better in prostate cancer. 

And we’re finding out that in prostate cancer there’s about 20 to 25 percent of patients that appear to respond to this type of treatment. But these are patients that don’t have a lot of bone metastases. And these immune checkpoint inhibitors are given in combination. So, they’re not given alone. They’re given with either a combination of anti-CD34 and anti-PD-1 or some other form of that. 

Katherine:

Prostate cancer research really can only move forward through clinical trials and patient participation in those trials. Can you briefly explain what a trial is for people who may not be familiar with the term? 

Dr. Subudhi:

That’s a great question. My own father has prostate cancer. And he had the same exact question when he started his journey in that. 

And so, what I explained to him is that clinical trials are experiments. They’re experiments that are done in our patients.  

So, they’re drugs that are thought to mechanistically kill the cancer cell or at least change the environment around the cancer cell to help people live longer. But these drugs were actually tested in mouse models or in tissue models. And we don’t know if they actually work in patients. 

And so, in clinical trials, we’re actually testing whether these drugs are safe and whether they’re efficacious or beneficial to our patients. So, I want to be very clear. When patients go on clinical trials, we don’t know if it’s going to work on them. And that’s something that they should know that they’re showing a lot of courage and risk in joining these trials.  

But the other point I want to make is that every standard of care drug that is out there actually went through the clinical trial process, and they were approved because they showed benefit in a group of patients. 

Katherine:

Well, how can a prostate cancer patient benefit from participating in a trial? 

Dr. Subudhi:

One of the key benefits is that you get access to drugs that may actually prolong your life or even cure you and that you wouldn’t have access to in trials.  

And so, some of my patients, unfortunately, they’ve exhausted all the standard of care choices that are out there. And the trial’s the only option left versus leaving it up to natural causes of demise from prostate cancer. And so, clinical trials give other opportunities to potentially live longer and have a great quality of life. 

Katherine:

So, they could offer some hope. 

Dr. Subudhi:

Definitely. As far as I’m concerned, yes. And, actually, with my patients, I try to not wait while they’ve exhausted all the treatments to start them on clinical trials, because I feel like we may be able to save some of these treatments in our back pocket for when they’re too exhausted to be coming to our clinic so often. And so, I like to actually try to get them enrolled in clinical trials early on in their journey with prostate cancer. 

Katherine:

I’d like to define some clinical trial terminology to help patients further understand the process. Let’s start with the phases. What occurs during each phase?  

Dr. Subudhi:

So, great question. Phase I is the safety phase. So, all we’re trying to do is find the right dose of the drug that is actually safe to give in the patients. And we’re looking for the maximum tolerated dose. And once we find that dose, then we use that dose to go to Phase II of the trial. And Phase II trials are looking at efficacy. So, looking to see whether the trial is giving you any clinical benefit, meaning the cancer’s shrinking or even disappearing. 

Katherine:

Go on.  

Dr. Subudhi:

And then the third phase is Phase III where you’re testing the current drug, experimental drug, to either standard of care or to a placebo to see whether or not you get a benefit, either a progression-free survival benefit or overall survival benefit. And so, those are the three phases of clinical trials.   

Katherine:

What are the different types of clinical trials? 

Dr. Subudhi:

So, they’re controlled trials. Actually, I should back up. So, there’s open-label trials where everyone that enrolls in the trial will get the experimental drug. So, there is no control arms in these trials. Then there is the control trials where you can either get the drug, or you may get a placebo or standard of care drug.  

There are some trials that allow for crossover, meaning that if you’re in the placebo or standard of care arm, if your cancer progresses, you can actually cross over and get the experimental drug. But I just want to be clear that not all clinical trials have crossover. And if you’re in a control trial, I think that’s an important question to ask your doctors about that. 

But the reason why we do the control trials is that we’ve learned that using historical controls – for example, we’re doing a lot of combination studies with chemotherapy, such as docetaxel (Taxotere), which was FDA-approved in 2004. So, if we’re using historical data from almost 20 years ago, it’s not the same thing as our patients that are being treated with docetaxel now, because their treatment landscape has changed so much, and our patients have changed so much. 

And so, for that reason, control trials give us a better sense of how effective this experimental drug is doing as opposed to comparing it to a historical perspective. 

Katherine:

What other types of clinical trials are available? 

Dr. Subudhi:

So, there are a few other options. So, we talked about open-label where everyone’s guaranteed to get the drug. We talked about a controlled study where you will either get one drug or another. And another type is a randomized trial where a computer decides whether or not you’re going to actually get one drug versus another. It’s not your doctor because a lot of people think that I’m making that decision, and I’m not. It’s actually a random computer. 

And some trials have 1:1 ratio, meaning a 50 percent chance that you’ll get the experimental drug versus the control drug. But other trials have 1:2 ratio or 1:3 ratio. So, that’s something that, again, you have to ask your physician of how these trials are being randomized. 

Katherine:

Well, in a randomized clinical trial, the patient isn’t going to know what drug they’re being given. 

Dr. Subudhi:

Actually, that’s not true. 

Katherine:

Oh, it’s not. 

Dr. Subudhi:

So, you bring up a great question. So, there’s a double-blind randomized clinical trial where not only the patient doesn’t know, but even the physicians and the nurses. No one except for the pharmaceutical company that’s running the trial actually knows who’s actually getting which drug. And it’s only towards the end of the trial that we unblind, and then we share that information. Well, the pharmaceutical company first shares it with the medical team who then shares it with the patient. 

Katherine:

I see. Are there other common clinical trial terms that you think patients should know about and understand? 

Dr. Subudhi:

I think for now those are… 

Katherine:

…they’re the most important?  

Dr. Subudhi:

I think to me those are the most important. And I think that sometimes too much information can bog us down.  

Katherine:

Well, speaking of information, there is a lot out there, some of which may not be very reliable. And that could lead many patients to having misconceptions about clinical trials. Let’s walk through a few common concerns we’ve heard from our community about trials. 

One frequent question is – will I receive a placebo instead of a real treatment? And, first, I’d like you to define placebo. And should this be a concern for patients? 

Dr. Subudhi:

Right. So, placebo is a drug that looks similar to the experimental drug. For example, if the experimental drug is a blue pill, then the placebo will be a blue pill. But it will be a pill that should have no known biological activity.  

If the experimental drug is given intravenously and you get it in a liquid bag, then the placebo will also come in a liquid bag. So, it will look the same. And that’s why both the medical team as well as the patients or their families will not know which drug the patients have received, meaning the experimental drug or the placebo. But the placebos are meant to not have any biological activity. 

Katherine:

So, it shouldn’t be a concern to patients then.   

Dr. Subudhi:

Well, the concern that most of my patients share with me when they hear about placebo-controlled trials is, “Well, if I’m not going to get the experimental drug, why should I do this? I mean what benefit does it have for me?” And so, I tell them that one of the benefits is that we are watching you very carefully. 

Because we don’t know sometimes which drug you’re getting. But in some control trials, like a randomized control trial, we will know because I’m not blinded.  

If you’re in the arm that’s only getting chemotherapy, well, you know you’re not getting an oral pill. So, it’s very clear to the patient what they’re getting. But if they’re getting an oral pill that’s a placebo, we’re watching them very carefully.  

So, we’re watching the patients very carefully in these placebo-controlled trials. And they’re coming in often so that we’re not going to miss any devastating things happening from the cancer. In fact, we’ll pick it up earlier than if they were just getting a standard of care outside of a trial. And for that reason I tell that my patients, “Don’t be worried.” And I always make sure that I have a backup plan. 

So, the backup plan is either they’re going to cross over, meaning the trial allows for them to cross over to get the experimental drug. Or I have another trial that I know that they will qualify for. Or the third alternative is that I actually have a standard of care drug that I’m ready to give them the second I have it so that they don’t have to have those concerns. 

Katherine:

That’s really great information to have. Patients also often have questions about safety. So, what are the risks of clinical trial participation? 

Dr. Subudhi:

So, safety is a major issue, especially more into the Phase I. The Phase I trial, if you remember, are the trials where we’re dose escalating, meaning we start off with a small cohort of patients, maybe three to five patients. And we give one dose of the drug. We see if it’s safe. If it’s safe, then we go to the next dosing level. And we just keep going until we find a dose that may be too toxic or too unsafe for our patient. 

So, in the Phase I, we have less information, especially in the first-in-human drugs. But in those cases, we are watching you carefully to make sure that nothing bad happens to you. 

But the problem with those trials is it requires a lot of time at the institution or with your doctor. For example, I’m doing a bispecific trial where we have to keep the patients inside the hospital for eight days, purely for safety reasons. They’re not getting the drug for all eight days. But we’re just keeping them under observation so in case anything bad happens we’re ready to react because we know that if something bad happens at their home in that first eight days, it could actually risk their lives. 

So, in those cases, some trials, if we’re concerned about safety, you’ll be spending more time in the doctor’s office or in a hospital being evaluated. So, that’s the one negative. But sometimes, the trials that can be more exhausting as far as the amount of time it takes you away from your home and family are the ones that have the most reward. 

Katherine:

Well, what protocols are in place to protect patients? 

Dr. Subudhi:

So, when they sign up for a protocol, we are instructed to give them our best information. So, let’s say it’s a first-in-human drug. Well, usually, first-in-human drugs are tested in other mammals, such as monkeys, and we look for toxicities there. And we have signs of what’s going to happen. Sometimes, a first-in-human drug is part of a class of drugs, like I talked to you about T-cell bispecifics. 

Well, there’s several T-cell bispecifics out there. And we’ve learned that this class of drugs has a unique set of side effects that they all tend to have. Some have it more, and some have it less. 

But when we’re discussing this with you or the patient, we are actually going to go through each and all of these side effects. Now, me personally, my patients that go on my trials, they all get my cellphone number so they have 24/7 access to me because I know they’re taking a risk. And it’s a lot of courage to go on these trials. And it’s scary. And I want to make sure they don’t feel like they’re ever alone. 

Katherine:

Another common concern we hear is that a clinical trial is only considered when there are no other treatment options available for a patient. What are your thoughts on this? 

Dr. Subudhi:

There’s a lot of my colleagues in the field that feel that way. And I know a lot of patients’ misconceptions are also that way. And that’s partly because of Hollywood and movies and TV shows that we watch. But I think that many people, especially in the medical field, think of clinical trials as the last resort. 

And I actually disagree with that. I think that I like to actually start my patients with one or two standard of care treatments. But after that, really start putting clinical trials in between. And we have to remember that there’s not always a clinical trial available that the patient actually meets the criteria for.  

So, it’s always disheartening in clinic when I meet someone for the very first time who was referred to me because they exhausted everything. And we just don’t have any clinical trials available, or they’re so weak from the cancer and all the prior treatments that they don’t qualify for a clinical trial. And then I really don’t have anything else to give them.  

So, my personal approach is to try to put clinical trials in between and always have something in my back pocket so that if they get a bit exhausted or they want to spend more time with friends and family, they can get the standard of care treatment. 

Katherine:

If a patient is interested in participating in a trial, what’s the best way to find out which trials might be available for them and right for them? 

Dr. Subudhi:

So, that’s a great question. I think number one is always ask your oncologist, and they’re a great resource. But also, there’s websites. So, for different types of cancer – so, example, I do prostate cancer. So, the Prostate Cancer Foundation or PCF.org is a wonderful resource that will give you a list of cutting-edge trials. 

In addition, the government has clinicaltrials.gov. And that’s where you can actually type in your cancer type and different criteria, and you’ll get a list of trials. 

Katherine:

That’s good to know. What questions should patients ask their healthcare team when considering joining a trial? 

Dr. Subudhi:

I would ask them, “Would you do it yourself if you were in my situation?”  

Katherine:

Very good. 

Dr. Subudhi:

I think that’s a very important thing to ask.  

Katherine:

Are there barriers that interfere with patients’ access to clinical trials? I think you touched on this but maybe if you have anything to add.

Dr. Subudhi:

Yeah. So, travel can be a major barrier. And that’s something that the pharmaceutical industry understands. And, therefore, some of the trials, especially the multicenter trials, actually allow for travel cost. That sometimes includes flights, driving, hotels, food.  

So, that’s something that’s important to ask because sometimes when we’re thinking about clinical trials, we’re so anxious in the doctor’s office. And then it’s not until we go back home when we’re trying to figure out how do we get the resources to come so frequently. You’ll find out that’s sometimes travel costs. 

The other thing is underrepresented minorities are something that we’ve been doing a relatively poor job recruiting to our clinical trials. Part of that is just from history that we didn’t have the safety rules in place that we do now. And underrepresented minorities were affected negatively in some of the earlier trials.  

And the other thing is just the resources of getting to and from their homes to our cancer site as often as they need to because they may be the sole breadwinner in their homes and things like that. So, there are resources to try to help do this. But I still think we have to do a better job. 

Katherine:

Can trials be coordinated between a local doc and the institution? 

Dr. Subudhi:

So, most trials cannot. Most. But there are some that can. So, if it’s a standard of care treatment, sometimes we can have the safety visits done with the local doctors. But every time they’re going to get the treatment they have to come see us at the institution that is actually running the trial.   

But most of the time, what I tell all my patients is, “I want them to have a local doctor.” Because if there’s something that happens in the middle of the night, I want to be able to say, “You’re going to go to this emergency room where this doctor works.” And then when they go there, as soon as they get admitted into the emergency room center, I talk to the ER doctor, and I say, “This is what I want to be done. These are how these drugs work.” 

Because they’re not going to know what these experimental drugs are. They’re not available in the community. So, I just think it’s important to have communication, especially for our patients that are out of state. MD Anderson is in Houston, Texas. And Texas is so big that a lot of my patients live six to eight hours away, and they’re still in Texas. 

Katherine:

Oh, wow. So, what are your thoughts on what could be done to overcome the barriers that some patients are experiencing? And are there resources available?  

Dr. Subudhi:

So, the pharmaceutical companies are putting in more financial resources as well as a diversity resource. And when I say diversity resources, those outreach programs just to make sure that the communities that are underserved are hearing about the clinical trials because if you don’t hear about it you’re never going to join it. So, one thing is just knowledge. 

And then, number two, we’re trying to create financial resources. For example, there’s Angel Flight as one example where they will pay for the flight for you. And they’ll put you on maybe a chartered plane or something or a smaller plane to defray the cost of traveling by air. So, there are things out there, but we still need a lot more. 

Katherine:

But one thing patients could do is talk to their healthcare team about what resources are available for them.  

Dr. Subudhi:

Absolutely. Absolutely. 

Katherine:

Before we end the program, Dr. Subudhi, I’d like to get your final thoughts. What message do you want to leave the audience with related to clinical trial participation? 

Dr. Subudhi:

First of all, thank you for even thinking about it. That’s the one big step. And for those of you who actually take the next step and actually join a clinical trial, again, thank you for being so brave. 

I think it’s a gift that you’re giving to other fellow patients with cancer. And it’s also a gift that you’re giving to the scientific and medical community, because we are learning by your participation in the trial. And I want you to know whether the trial worked for you or does not work for you, regardless, we’re going to learn something that’s going to help change outcomes in your cancer. 

Katherine:

Dr. Subudhi, thank you so much for taking the time to join us today. 

Dr. Subudhi:

Well, thank you. I really appreciate it.  

Katherine:

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. 

And don’t forget to take the survey immediately following this webinar. It will help us as we plan programs in the future. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thank you for being with us. 

What Does Active Surveillance Mean for Prostate Cancer?

What Does Active Surveillance Mean for Prostate Cancer? from Patient Empowerment Network on Vimeo.

Prostate cancer care may include active surveillance, but what does it mean exactly? Expert Dr. Tanya Dorff explains this approach and how it is used to monitor patients with prostate cancer.

Dr. Tanya Dorff is Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope. Learn more about Dr. Dorff.

 

Related Resources:

How Is Early Stage Prostate Cancer Treated

What Are Advanced Prostate Cancer Treatment Options


Transcript:

Dr. Dorff:

Active surveillance is different than what some people think it is. So, some people think it means we’re not going to treat the cancer, that we’re just going to let it take its natural course. It’s actually quite active, as the name implies. We’re really trying to get to know a person’s cancer and understand whether it is a cancer that will ultimately need to be treated, in which case we will intervene with definitive treatment, whether that be radiation or surgery, but the goal is to find those patients whose cancer is not very aggressive and may never need to be treated so that they can avoid the possible risks that come from definitive local therapy. 

Katherine:

So it’s more like a watch-and-wait situation? 

Dr. Dorff:

But it’s…I, again, view it as a little bit different than that. Watch and wait is “let’s just let it do what it’s going to do.” Active surveillance is what I call a getting-to-know-you period. Let’s understand whether these clinical features that have signaled that your cancer may be low-risk, may not need treatment – let’s see if that really plays out, let’s make sure we haven’t missed anything, and if your cancer needs treatment, we’re going to treat it. 

Thriving With Prostate Cancer | Tools for Navigating Care and Treatment

Thriving With Prostate Cancer | Tools for Navigating Care and Treatment from Patient Empowerment Network on Vimeo.

How can you thrive with prostate cancer? Dr. Tanya Dorff discusses prostate cancer treatment and developing research, side effect and symptom management, and shares advice and resources for coping with emotional issues.

Dr. Tanya Dorff is Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope. Learn more about Dr. Dorff here.

See More from Thrive Prostate Cancer

Download Resource Guide

Related Resources:

Tools for Partnering in Your Prostate Cancer Care

Tools for Partnering in Your Prostate Cancer Care 

Understanding Advanced Prostate Cancer Treatment Approaches

Understanding Advanced Prostate Cancer Treatment Approaches 

What Is Advanced Prostate Cancer?

What Is Advanced Prostate Cancer? 

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is part of our Thrive series, and we’re going to discuss tools to help you navigate life with prostate cancer. Before we meet our guest, let’s review a few important details. The reminder email you’ve received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar.

At the end of this program, you’ll receive a link to a survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.

Well, let’s meet our guest today. Joining me is Dr. Tanya Dorff. Dr. Dorff, welcome. Would you please introduce yourself?

Dr. Dorff:

Thank you. Hi, I’m Tanya Dorff. I’m a medical oncologist and section chief of the genitourinary cancer program at City of Hope, which is near Los Angeles, California.

Katherine:

Excellent. Thank you so much for taking the time to join us today.

Dr. Dorff:

My pleasure.

Katherine:

Like all of the webinars in our Thrive series, we start with the same question. In your experience, what do you think it means to thrive with prostate cancer?

Dr. Dorff:

Well, that’s a big question. As a medical oncologist, my job is to try to strike a balance between cancer control and quality of life, and I guess that’s how I would put thriving with prostate cancer. It’s not always just about what is the PSA doing, but it’s also about, ‘How are you getting around your day-to-day life activities, and are you able to do the things you enjoy?’ So, treatments can be very effective. They can also have significant side effects, and we spend a lot of time day in and day out trying to help men strike a good balance.

Katherine:

Thank you for that, Dr. Dorff. Let’s move on to how prostate cancer is treated. This webinar is mainly focused on advanced prostate cancer. But before we get into treatments for more advanced disease, let’s do a quick overview of early-stage prostate cancer options. First, some prostate cancer patients are often put in active surveillance. What does that mean?

Dr. Dorff:

Active surveillance is different than what some people think it is. So, some people think it means we’re not going to treat the cancer, that we’re just going to let it take its natural course. It’s actually quite active, as the name implies. We’re really trying to get to know a person’s cancer and understand whether it is a cancer that will ultimately need to be treated, in which case we will intervene with definitive treatment, whether that be radiation or surgery, but the goal is to find those patients whose cancer is not very aggressive and may never need to be treated so that they can avoid the possible risks that come from definitive local therapy.

Katherine:

So it’s more like a watch-and-wait situation?

Dr. Dorff:

But it’s…I, again, view it as a little bit different than that. Watch and wait is “let’s just let it do what it’s going to do.” Active surveillance is what I call a getting-to-know-you period. Let’s understand whether these clinical features that have signaled that your cancer may be low-risk, may not need treatment – let’s see if that really plays out, let’s make sure we haven’t missed anything, and if your cancer needs treatment, we’re going to treat it.

Katherine:

Okay, that’s good to know, thank you. When it is time to start treatment, what types of approaches are available for early-stage prostate cancer patients?

Dr. Dorff:

Localized prostate cancer or early-stage prostate cancer can be cured with either surgery or radiation, and we actually view these to be equally effective options. Sometimes people have the misconception that if they’re getting radiation to treat their localized prostate cancer, they’re being relegated to a noncurative or a less effective option. It’s actually not the case. We don’t have truly good, randomized, head-to-head studies.

You can find retrospective studies, people looking back at 2,000 patients treated at this institution or that institution, and you can find a study that pretty much says whatever you want it to. You can find some that say surgery’s better, some that say radiation’s better, but in sum, we sort of view them as being equally effective options. And so, they just have different side effect profiles, and so, we often counsel patients who are considering which local treatment to receive to look at what their current urinary function is, what their goals are for their long-term function, both urinary and sexual, and use that as a guide, as well as their age, their other health conditions, and those kinds of factors. 

Katherine:

Let’s turn now to how advanced prostate cancer is treated. First, what does it mean to have advanced disease?

Dr. Dorff:

Advanced prostate cancer signals cancer that’s come back after curative intention or has presented de novo in a way that means we don’t currently have a tool to cure it. That’s at least how I view advanced prostate cancer. You could take a broader definition and consider some high-risk localized patients who need multimodal therapy, but to me, it’s really signaling a shift from something we’re aiming to cure versus something we’re aiming to manage, so that can manifest just as a PSA that’s rising, what we call biochemical recurrence, or it can manifest as visible metastatic disease.

Katherine:

What does “locally advanced” mean?

Dr. Dorff:

So, “locally advanced” means that it hasn’t metastasized, but it might be involving the local structures, like the seminal vesicles or the bladder or some of the regional lymph nodes, the pelvic lymph nodes.

Katherine:

How is advanced prostate cancer treated?

Dr. Dorff:

The cornerstone of treatment for advanced prostate cancer has really been hormone therapy. I think there’s a lot of negative stuff out there on the internet about hormone therapy that I think does a disservice to patients because hormone therapy is truly very, very effective and, for many men, can be quite livable.

I have patients who live more than a decade on hormone therapy, and they’re running their businesses and they’re raising their grandkids, they’re traveling, they’re running 10Ks, they’re doing all the things that they might want to be doing. That’s not to say there aren’t side effects, but hormone therapy is an effective cornerstone, and I really hope people won’t dismiss it offhand because of the negative things they’ve heard or read about it.

Katherine:

What about other treatment classes?

Dr. Dorff:

Most of our other treatments are really layered on top of hormone therapy. We may get to a point – 10 years from now, I don’t know, sometime in the future – when we don’t start with the hormone therapy, so a lot of patients come in asking about the new radiopharmaceutical, the Lutetium-177-PSMA that got approved last year, or about whether chemotherapy can be used. They can be, but they’re really layered on top of hormone therapy, so the hormone therapy is the first treatment, it’s the most effective right now, and then it’s continued as we swap out – we add a novel hormonal agent like abiraterone (Zytiga), or enzalutamide (Xtandi), or one of the others.

When that is no longer effective, we swap that out, we might use chemotherapy or the radiopharmaceutical. There’s also an immunotherapy that’s been around for more than a decade called sipuleucel-T, and now there’s the targeted therapies – the PARP inhibitors – as well for select patients.

Katherine:

Where do clinical trials fit into treatment?

Dr. Dorff:

That’s a great question. I’m so glad you asked. Clinical trials some people mistakenly believe are your last choice, like you’ve gone through every single treatment we have, and then you go to a clinical trial. That’s not the case. Some of the biggest advances in prostate cancer have been when we’ve taken drugs that work in a more advanced resistance setting, like a second- or third-line, and when we move them right up front, first-line, we dramatically amplify their benefit. We dramatically improve survival.

So, if we don’t think about a clinical trial in the first line, we’re going to miss the opportunity to not only develop those new treatment paradigms, but actually participate in them ahead of when they become the new standard of care down the road.

Another misconception that people have often about clinical trials is that they are always randomized, there’s always a flipping of the coin in assignment of different treatments, and that they may include a placebo. So, most of our clinical trials at this point do not include placebo. Because we have so many effective treatment options, we’re more and more frequently comparing either two drugs against one, so everyone’s getting at least one effective drug, or we’re not comparing at all, but everyone’s getting some new treatment or some combination of treatments when we’re working out dosing in that scenario, like a Phase II.

So, clinical trials are really an option at any stage of prostate cancer, even at diagnosis for localized disease all the way through, and truly, I hope people would consider looking at those as options because that’s where some of the most innovative treatment options are going to become available to them.

Katherine:

Yeah. What sorts of questions should patients ask their doctors about clinical trials?

Dr. Dorff:

There are a few really basic things to ask about any clinical trial that you’re being presented as an option. One is is there a randomization? Is there a treatment assignment where some people get one treatment and some people get another treatment? Another one is is there a placebo? I think if we just get those questions up front, right away, then people may be more open to hearing what’s happening in the rest of the trial.

Our informed consent documents are reviewed by ethical consultants and are really meant to inform about risks more than benefits, so the other thing to really ask the provider is what’s the goal of the trial, because that’s often not clearly communicated in an informed consent. Why did the people who designed this trial think it was a good idea? Is there science behind it, is there clinical data behind it, and do you think this is something that, in the future, could end up being the new way that prostate cancer is treated?

What is it about me that you think makes me a good candidate for this trial? What’s been your experience? – even though it’s more anecdotal, but it’s often nice to hear from a physician “I have patients on this trial, they’re having these types of side effects, they’re having these types of benefits, and we can’t know what will happen for you, but at least I have a sense of how things are going on this trial.”

Katherine:

Yeah, those are great questions. What about cost? Is that a question that patients should ask about?

Dr. Dorff:

Patients often do ask about that. Costs are really complex in this medical care landscape that we have in the United States. Clinical trials – I think there’s a lot of misunderstanding about costs. Some people think that everything is paid for by the clinical trial, which is not true.

There is a system by which we assign things that will be paid for by the clinical trial – anything that’s novel and only being done as part of the trial versus things that would be done anyway if you were not in the trial and if you were just receiving regular care, such as your PSA test, your clinic visit, your CAT scan potential, or your bone scan.

So, there are some costs that are not covered, and in that case, if a patient has an insurance plan where they have copays for a clinic visit or for a CAT scan, those aspects that are not felt to be unique to the clinical trial and are getting billed to standard insurance – that means they’re still going to have those copays, but anything that is unique, if there’s an extra set of scans, if there are extra clinic visits, those get billed to the study, and the patient should have no extra cost on that basis.

Insurance companies should view clinical trials very favorably, because they’re often getting some clinical care paid for. They’re getting extra treatment at no cost, so anything that’s new on the treatment plan in the clinical trial is free to the insurance company on the patient, it’s paid for by the study, so it’s a good deal, generally speaking, and more importantly, there’s legislation that really seeks to ensure that regardless of your insurance, you should have access to clinical trials because they are felt to be often the best way to have your cancer treated.

Katherine:

Yeah. Dr. Dorff, are there emerging therapies that are showing promise?

Dr. Dorff:

There are a lot of emerging therapies. People all over the country and all over the world are working to find new and better ways to treat prostate cancer. So, the breakthrough radiopharmaceutical last year of the Leutetium-177-PSMA is the first, but not the last, I believe, in that field. There are other antigens we can target rather than PSMA, there are other particles we can use rather then Lutetium-177, and so, there are currently clinical trials looking at different constructs.

Take a winning strategy, and then tweak it a little bit to see if you can make it even better, right? Similarly, the PARP inhibitors, which are FDA-approved for prostate cancer, are being studied in different types of clinical trials to try to expand the number of patients who can benefit from them and amplify the benefit – so, moving them earlier, increasing the types of patients who are appropriate.

And there are additional targeted therapies, like the PI3-kinase AKT inhibitors, the CDK-46 inhibitors, that are being looked at in combination with our standard hormonal drugs that I think could end up being big advances depending how the results play out. There’s a novel class of drugs, the antigen receptor degraders, which also look tremendously promising in clinical trials and are in Phase III testing in some cases, and then, some additional ones are a little earlier in testing.

And then, there’s immunotherapy, which is at the heart of my research at City of Hope. Immunotherapy offers the promise of using your own immune system to control the cancer or eradicate the cancer, so we’re looking at different strategies, from oncolytic viruses, to bi-specific T-cell-engaging antibodies, to CAR-T cell therapies in hopes that we will find something that can really induce a big, deep, durable, long-lasting remission for patients.

Katherine:

That’s really promising. What about treating symptoms of the disease itself, like bone pain?

Dr. Dorff:

Bone metastases are the predominant pattern of spread, and so, what really drives the story for a lot of our prostate cancer patients during their journey with cancer has to do with bone complications – not always pain, but unfortunately, there can be pain pretty frequently.

So, we start by trying to protect the bones early on. We know that when we use our hormonal therapies, osteoporosis can develop, so we want to avoid that. I’ve had patients where their cancer was well-controlled, but they had an osteoporosis fracture that they were miserable from, so it starts at the beginning, at protecting the bones, checking a bone density scan and/or using a bone-supportive agent like zoledronic acid (Zometa) or denosumab (Xgeva), and then, in the metastatic setting, as the disease progresses, we intensify that use of bone-supportive agents.

We sometimes end up using radiation therapy, which is primarily external-beam traditional kind of radiation, but there is also the radiopharmaceutical Radium-223 (Xofigo), which delivers the radiation kind of more internally through the bloodstream to areas of the bone that are active from the prostate cancer, and sometimes we end up needing something even like surgery, but the bones are a major part of the story.

Katherine:

Yeah. What about sexual dysfunction? Are there approaches that can help?

Dr. Dorff:

So, this is generally an area that’s managed more by urology. There definitely are things that urologists do to help patients who have lost sexual function due to prostate cancer treatments. They can involve medicines, they can involve slightly more invasive things like a suppository or an intracavernosal injection. There are also more mechanical ways, like a pump device or a penile implant, but generally, anything beyond the first level, which is Viagra, will be handled more by a urologist than a medical oncologist.

Katherine:

What is palliative care, and how can it help men with prostate cancer?

Dr. Dorff:

Palliative care is something that we think about more towards the end of life, where we’re focusing on cancer symptoms more than treating cancer. However, some studies have shown – very prominent studies – that early palliative care in some malignancies is associated actually with better survival, meaning that paying attention to the patient’s symptoms is actually a really important part of keeping them well and keeping them alive as we treat the cancer.

So, more and more, we’re starting to integrate palliative care earlier in the disease.

I think that can sometimes signal a little alarm for patients – “Oh, I’m being referred to palliative care, that means my doctor doesn’t really think they can treat my cancer anymore” – and it’s gonna take some education to really help people transform their thinking about palliative care as a strategy that’s not for the end, but something that really should be part of our treatment all along.

So, our palliative care team, or what we call supportive medicine at City of Hope, uses treatments to manage pain. They have a broader spectrum, they’re more focused on all the different modalities to treat pain, so an oncologist or urologist can treat pain, but when we refer to palliative or supportive medicine, you get just that extra expertise, especially if people are having a lot of side effects from pain medicines, but our supportive medicine doctors aren’t only pain management doctors.

They help with other symptoms, like nausea or constipation, to some extent urinary symptoms for my prostate cancer patients, although we rely heavily on urology for that, and also just the existential, or spiritual, or emotional components.

Our supportive medicine team typically includes not only an MD, an advanced practice provider like an NP, but also someone from psychology, someone from social work, because dealing with cancer is really stressful and challenging, and in an ideal world, palliative care is not only taking care of the symptoms of the cancer that are physical, but also helping the whole being, the whole family unit that’s going through this experience have less emotional distress as well.

Katherine:

Yeah. Well, that leads us perfectly into the next section, which is about emotional support. Beyond treatment, another large part of thriving with prostate cancer is dealing with the emotions that come along with the diagnosis, like fear and anxiety. Whether it’s the stress of being in active surveillance or worrying about progression, many patients need help coping emotionally. Why do you feel it’s so important for patients to share these emotions with their doctor or their healthcare team?

Dr. Dorff:

I think it’s a conversation that’s not held enough between patients and their physicians, and if we don’t remember to ask our patients, we will just focus on the medical because that’s our main wheelhouse, that’s what we’re best at. So, if a patient brings forth that they’re having some emotions related to the cancer, it is helpful to us in remembering – we ought to do everything 100 percent all of the time, but let’s face it, we’re physicians with time pressures and certain areas of comfort and expertise. So, if a patient brings it up, that is super helpful because then we know someone’s needing assistance, which probably every patient is, whether they tell us or not, but that triggers us to then offer appropriate referrals.

And also, it tells us they’re open to it. If we have to ask every patient, “Are you having any emotional distress?”, even if someone answers yes and then we make a referral, they may not have actually been ready for it or open to it. So, having the patient come forth and raise that, I think, is really helpful and important.

Katherine:

Many prostate cancer community members are interested in learning more about their cancer and are hungry for information. For men who are newly diagnosed, are there educational resources that you recommend?

Dr. Dorff:

There are several good patient-focused or patient-facing educational resources for cancers generally. So, the American Society of Clinical Oncology, or ASCO, runs a patient-facing website called Cancer.net.

They also produce a lot of educational materials. So, for instance, we have some handouts in our clinic rooms produced by ASCO that really just help patients understand, okay, when you’re having diarrhea related to cancer treatment, here are some strategies. So, there’s lots of good information from them. There’s also a group specific for prostate cancer called Prostate Cancer Foundation.

So, they are an organization that works a lot in funding new research in prostate cancer, but they also put out some really helpful publications, again, that are aimed at prostate cancer patients, and really kind of covering the whole spectrum of disease, as well as more holistic aspects which are really important, things like diet and exercise and how that plays into overall wellbeing and health during prostate cancer treatment. So, we keep some of those little booklets in our rooms as well to hand out to patients, but they’re probably available by request online as well on one of the Prostate Cancer Foundation websites.

Katherine:

Yeah. What about resources for prostate cancer patients who are already really knowledgeable about their disease and want to stay up to date on the latest research and treatment? What’s available for them?

Dr. Dorff:

There are some conferences that seek to educate patients on a little higher level. It can be challenging because not every prostate cancer patient is at the same place, but they can look for some of those conferences. Frankly, they can follow Twitter or some of the other social media.

Sometimes prostate cancer support groups also will bring in speakers who try to provide updates about emerging treatments, or where the research is going, or where the field is going. So, most big cancer centers are gonna have a support group.

Obviously, it’s very variable, and sometimes they may focus more on the psychosocial aspects, but I do think a lot of them will include people like me, who are just trying to connect with the cancer patients on various levels about the latest and greatest.

Katherine:

We received some audience questions prior to today’s webinar, and I’d like to go through some of them with you. Bob asks, “Does androgen deprivation therapy cause cognitive issues?”

Dr. Dorff:

So, androgen deprivation therapy is another way of saying hormone therapy. We’re lowering testosterone, which is an androgen, and the question about cognitive issues is a good one. If you look in the literature, it’s not been well documented, and part of that is because our patients tend to have age and other comorbidities that can lead to changes in cognition happening at the same time as they’re being treated for prostate cancer, but also because the tools just haven’t been very good.

The tests where we measure how your brain is working have traditionally not been very good. There are some better tools that have been developed, and we’re hoping to be able to – with some ongoing studies – better define are there cognitive changes? If so, how severe are they, how common are they, are they more common with one drug versus another? Very basic questions.

I will say in my own practice, after 15 years of treating prostate cancer, I do believe that some patients experience cognitive changes during ADT. They can be mild, like taking longer to remember someone’s name or walking into a room and forgetting why you’re there, which, frankly, happens to all of us when we’re not having our best days, but obviously, I do see that a little bit more with prostate cancer patients who are receiving hormonal therapy.

For some of my really high-functioning patients, it can be helpful to use a drug that treats attention because some of the cognitive dysfunction actually ends up being an issue with attention. So, we use drugs like methylphenidate (Ritalin) or dextroamphetamine mixed salts (Adderall) to support patients who need to be really focused, and I’ve had many patients tell me that that has made a huge difference for them, so it’s not going to solve the overall changes that may happen in the brain on the basis of the hormonal deprivation, which we know happens from animal models, but it can help in the short term so that men can continue to function at a high cognitive level, despite ADT, when needed.

Katherine:

Yeah. George wants to know, “Are there any advances in imaging that patients should know about?”

Dr. Dorff:

Yes. So, the PSMA PET scans – so, these are a nuclear medicine imaging that looks for prostate cancer using a protein called PSMA, and there are several of them, there’s the F-18-based one called Pylarify, and then there are the Gallium-68 versions, Illuccix and Locametz, so those have been revolutionary. They can see prostate cancer in much smaller quantities, so we use them a lot for rising PSA after prostate surgery or radiation to see where is his small amount of cancer, and hopefully, we can treat it better by seeing it earlier.

They are also now being used to select patients for potential benefit from a treatment like Lutetium-177-PSMA, which obviously won’t work if the cancer doesn’t have that protein, so the imaging helps see who’s got the protein, who can benefit from the treatment. So, that’s the biggest imaging advance. There are some others, like using MRI fused to ultrasound for prostate biopsy at diagnosis. There’s also another kind of PET scan called a fluciclovine PET scan, which we still sometimes use because not 100 percent of prostate cancers have PSMAs, so sometimes we need something a little bit different.

Katherine:

Antonio had this question. “I heard that statins – cholesterol-lowering drugs – could help fight prostate cancer. Is that true?”

Dr. Dorff:

There’s been a lot of interest in the statins because in addition to having those positive effects against cholesterol, which are helpful when hormonal therapy that we use for prostate cancer disrupts our lipids, they have these anti-inflammatory properties that are being looked at in a number of different research avenues.

And then, there has also been a new, evolving understanding that they interfere with some hormone-binding compounds in the body, and so, could augment the effect of androgen deprivation therapy.

So, there has been interest in prospective studies because the literature we have right now is really retrospective, so we can’t really tell a patient which statin drug or what dose and for how long would be associated with a positive benefit, and we don’t really yet know how to use them proactively during someone’s treatment, but I will say if you’re starting on hormone therapy or ADT, having your lipids checked and getting on a statin if your lipids are not in a good range is really important anyway to just protect your cardiovascular health, and then, maybe we’ll find out that it does actually help your prostate cancer treatment be more successful as well, but I would say those data still need to be fleshed out a bit more.

Katherine:

Thank you for those answers, Dr. Dorff. I appreciate it. And please continue to send your questions to question@powerfulpatients.org, and we’ll work to get them answered on future programs. As we close out our conversation, Dr. Dorff, I wanted to get your thoughts on where we stand with research progress. Can patients truly thrive with advanced prostate cancer?

Dr. Dorff:

Absolutely. I would say in the 15 years I’ve been treating prostate cancer, I’ve really seen a transformation from a disease with a short lifespan and a lot of symptoms to a disease where people can actually thrive, living more than a decade even with advanced or metastatic prostate cancer, because the treatments have gotten so much better, and I think also potentially due to the increased awareness on the part of physicians about helping people stay healthy during their longer-term treatment. So, definitely, my patients today live longer and better than my patients did when I started treating prostate cancer.

Katherine:

Well, it seems like there’s a lot of progress and hope, then, for prostate cancer patients.

Dr. Dorff:

Absolutely.

Katherine:

Thank you so much for joining us today, Dr. Dorff. I really appreciate it.

Dr. Dorff:

Thank you. I hope people found it helpful.

Katherine:

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.

An Expert’s Perspective on Emerging Prostate Cancer Research

An Expert’s Perspective on Emerging Prostate Cancer Research from Patient Empowerment Network on Vimeo.

What do prostate cancer patients need to know about emerging research? Dr. Andrew Armstrong discusses developing treatments and their potential impact on prostate cancer care.

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

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Transcript:

Katherine:

Are there any recent developments in treatment and research that patients should know about? 

Dr. Armstrong:

Absolutely. I would say the number one research advance has been the use of these really strong hormonal therapies in earlier and earlier disease setting. So, you may have heard of drugs like Zytiga or abiraterone, or Xtandi or enzalutamide, apalutamide or Errleada, or derolutamide or Nubeqa. Those are mouthfuls. Those are very potent hormonal pills that when used in men with advanced disease improves survival. 

And the data has supported the fact that the early use of those agents extends life even more than waiting until hormone resistance develops.  

So, if you are unlucky enough to have metastatic disease and you’re in need of hormonal therapy, giving injections that lower testosterone, which is the fuel for most prostate cancers, and then blocking testosterone with some of these newer pills extends life by years, not months. And it does so with pretty good quality of life over time.  

Of course, there are negative consequences of having no testosterone, and it’s important as part of shared decision-making to review those side effects and how that can impact quality of life negatively while extending survival.  

So, that’s a major advance. Another major advance is genetic testing and personalized medicine. In men with advanced prostate cancer, it’s now uniformly recommended that all men get hereditary testing to figure out if they inherited prostate cancer risk genes.  

These are genes such as the BRCA I and II genes, BRCA II being the most common. And these are not just breast or ovarian cancer genes. It’s important for men to realize that you can inherit these from a mother or a father, that they can create risks for multiple cancers, not just female cancers, but prostate cancer in particular. 

And now we have guided therapies, targeted therapies that can improve survival in men with these certain mutations, and if you are found to have those mutations, your family members could be tested so that they could be screened, and cancer can be picked up earlier, and perhaps they could be cured rather than suffering the fate of a more advanced diagnosis. So, really important both for yourself and for family members. 

So, those are two major advances. A third one is imaging.  

Imaging keeps getting better and better. We used to just do CAT scans, bone scans, very insensitive tests that in men with advanced disease have a hard time seeing prostate cancer, even when it’s spread. But with the advent of new technologies, like PSMA PET scan, that got approved last year. So, very new technologies. That’s transforming the way we visualize where cancer may be hiding, and for men particularly that have high-risk disease or recurrent disease or even resistant disease, we’re using those scans to guide therapy. 

An Overview of Prostate Cancer Treatment Approaches

An Overview of Prostate Cancer Treatment Approaches from Patient Empowerment Network on Vimeo.

How is prostate cancer currently treated? Dr. Andrew Armstrong provides an overview of treatment options for prostate cancer patients across various stages of the disease.

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

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Transcript:

Katherine:

What are the treatment options that are currently available for prostate cancer patients? 

Dr. Armstrong:

It’s a really important question, and I would say it depends. In early disease, when cancer is picked up early, many patients are cured. Prostate cancer is the number one survived cancer in the United States. It’s important to realize that and kind of take a deep breath and realize that most patients beat prostate cancer. Only about one out of six men will suffer a relapse or develop metastatic disease or Stage IV disease that requires more of a lifelong journey of therapy. 

So, most men come into this because they’ve been screened by their primary care doctor. They had a high PSA, they underwent a biopsy, they were found to have cancer.  

And the first decision, particularly for example at our Duke multidisciplinary clinic, the first decision that we always share with the patient, and as part of shared decision-making, is we give information about prognosis and risk using the PSA level, the biopsy information, staging information if imaging is done.  

And then giving a category or a risk group to that patient can help them decide what are the options that are nationally recommended, internationally recommended by evidence-based guidelines. The most important decision is whether that prostate cancer needs treatment right now at all, and the initial observation or active surveillance is a very valuable “first do no harm” approach for men with very low risk or low risk types of prostate cancer. With a low-grade cancer, low PSA, low stage, and that’s about a third of all patients.  

That’s a huge number of men are told they have cancer, but they actually don’t need initial treatment. 

And they need to be explained to, why we’re not going to treat that cancer, why it’s so safe, and why mortality is not high in that patient population when we don’t treat it, and how we do active surveillance. For example, imaging with MRI, repeat biopsies. And a lot of patients do appreciate that because they’re not undergoing surgery or radiation and they’re not being harmed by those treatments. That would be called overtreatment. That’s not for everybody, though. 

So, just like prostate cancer comes in different flavors, treatments come in different flavors. So, there’s things where the Gleason score is higher, the stage may be higher, the PSA is higher, and the risk to the patient is higher. And when we get into that more intermediate- and high-risk situation, treatment is going to be necessary. But then we’ll have a menu of treatment options that is important to talk through. Typically surgery, radiation, sometimes alternatives to that. 

Sometimes combinations with hormonal therapy, which we call systemic therapy. The drugs that work throughout the body. 

Katherine Banwell:

What about for patients who have advanced disease? 

Dr. Armstrong:

The word “advanced” can mean different things to different people. Advanced can mean metastatic disease. It can mean disease that’s not curable. But advanced can also mean that it’s high risk. That the disease is still confined to the prostate, but it’s aggressive, and that if it’s not handled quickly with a multidisciplinary approach, for example, it has a high risk of occurrence.  

So, advanced disease can mean aggressive, in need of treatment. Sometimes it can be cured if it’s confined to the prostate. Sometimes it requires more than just one treatment modality, such as surgery followed by radiation, or radiation plus some of the newer hormonal therapies.  

For men with stage IV disease, that means disease that has left the prostate and gone to distant sites, we have very effective therapies that can still control this type of advanced disease for many, many years, so it is important to realize how far we’ve come with all of our therapies and to reassure the patient and their family about the good prognosis, even in the worst-case scenario, for many patients. 

Prostate Cancer Shared Decision-Making: How Does It Work?

Prostate Cancer Shared Decision-Making: How Does It Work? from Patient Empowerment Network on Vimeo.

Prostate cancer researcher Dr. Andrew Armstrong describes the benefits of the shared decision-making process and encourages patients to take an active role in their care.

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

See More from Engage Prostate Cancer

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Transcript:

Katherine:

Patients may have heard the term “shared decision-making” Let’s go into – let’s define it, though. What is it, and how does it work? 

Dr. Armstrong:

Sure. So, if you imagine you’re a patient faced with the daunting task of a new cancer diagnosis and trying to navigate decision-making around treatment, or whether you need a certain test, and those tests or treatments have harms and they have benefits, shared decision-making is really the process of communication. You know, open, transparent communication between the doctor or provider and that patient and their family and supportive spouse and others, significant others, so that everybody has complete information around the risks and benefits of a certain treatment course or management course.  

In prostate cancer, this would mean for a newly diagnosed patient, commonly first giving information about what the risks of their cancer might be, but then what the risks and benefits of various treatment algorithms might be, and explaining in ways that a patient can understand those different journeys.  

Dr. Armstrong:

And ultimately the patient makes a shared decision-making with the doctor that’s in their best interest. 

Katherine Banwell:

In your view, what role do patients have in care decisions and why should they feel empowered to speak up and be a partner in their care? 

Dr. Armstrong:

Sure. Just like there’s many different types of doctors, there’s many different types of patients, and you have some patients that have PhDs, you have some patients that are not even sure what cancer is, and it’s really important to empower every patient to understand at a level that will help them make a decision. And some patients wish to have those decisions made for them. I hear that a lot. Some patients really just want to ingest the information, not make a rash decision 

Maybe get three or four second opinions, travel around to really get the right decision. And sometimes it can take a very long time. But every patient has a different journey, and it’s important for the provider, the doctor or the nurse practitioner or the surgeon, to really understand that patient and their values to help them arrive at the decision for themselves. Because sometimes treatment decisions may have equal efficacy but different side effects.  

For example, in prostate cancer, the most common decision is between active surveillance or a radical prostatectomy or radiation of different forms, or the robot versus the open procedure, or intensity modulated radiation or brachytherapy. And these are complex decisions, and I’ve had patients go for months without making decisions. And the shared decision-making approach really can help patients make a decision as quickly as possible. 

So that they can move on and either be cured from their cancer or make the best treatment decision. 

Katherine Banwell:

Dr. Armstrong, why is it so important that patients tell their doctor about any symptoms they’re experiencing? 

Dr. Armstrong:

Certainly symptoms may or may not be related to the prostate cancer, and doctors are well-trained to sift through all of that. You know, back pain could be from a herniated disc or arthritis, but it could be a sign of metastatic disease. Weight loss could be a sign of other metabolic problems, but it can also be a sign of really advanced prostate cancer. Urinary symptoms could just be a sign of a big prostate, may have nothing to do with the cancer, or it could be a big tumor that’s blocking off your bladder.  

So, being transparent and open and just describing what symptoms and letting that physician sort through that with you to help understand what symptoms may or may not be related to the cancer, that’s really important.  

Thriving With Prostate Cancer: What You Should Know About Care and Treatment

What does it mean to thrive with advanced prostate cancer? Dr. Rana McKay discusses the goals of advanced prostate cancer care, reviews current and emerging treatment options, and shares advice for playing an active role in healthcare decisions.
 
Dr. Rana McKay is a medical oncologist at UC San Diego Health and an associate professor in the Department of Medicine at the UC San Diego School of Medicine. Learn more about Dr. McKay, here.
 
 

Katherine Banwell:    

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to focus on how patients can aim to live and thrive with advanced prostate cancer. We’re going to discuss treatment goals and the role patients can play in making key decisions. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well let’s meet our guests today. Joining me is Dr. Rana McKay. Dr. McKay, welcome. Would you please introduce yourself?

Dr. Rana McKay:     

Of course. Thank you so much for having me. My name is Rana McKay and I’m a GU medical oncologist at the University of California San Diego.  

Katherine Banwell:    

Excellent. Thanks so much for taking time out of your schedule to join us. Since this webinar is part of PEN’s Thrive series, I’d like to ask you from your perspective, what do you think it means to thrive with advanced prostate cancer?

Dr. Rana McKay:        

That’s a very good question and I think that’s what um, a lot of patients want to actually you know, do in their day-to-day existence. I think it means that they are combatting their disease. They’re taking a proactive role in um, you know, uh tackling um, their illness. They um, are uh, attentive to sort of doing the activities of daily living that really bring them joy and satisfaction and happiness and setting up a treatment plan that is a mutually agreed upon treatment plan with their clinician. That they have buy-in on. That their caregivers have buy-in on. That allows them to do the things that they love to do while keeping their cancer at bay.

Katherine Banwell:    

Okay. Thank you for sharing your insights. Before we move onto treatment, I mentioned that this webinar is focused on advanced prostate cancer. What does it mean for prostate cancer to be considered advanced?

Dr. Rana McKay:        

So, generally what that means is that the cancer may have spread outside of the body – outside of prostate to other parts of the body such as the bone or the lymph nodes which is a common location where prostate cancer um, uh, can go. Additionally, it may mean that the cancer may have come back after um, it was initially treated with an intent um, to cure um, a patient. But then you know the PSA demonstrates um, that you know, there’s a rise in the PSA and the cancer is recurrent.

Katherine Banwell:    

As you mentioned uh, appropriate treatment is part of thriving. We’re going to talk about treatment approaches. But first, how would you define treatment goals?

Dr. Rana McKay:       

So, you know when I look at defining treatment goals it’s focusing on what do we wanna achieve from the standpoint of the cancer? Meaning, you know, what are objectives that are associated with patients living longer?

And then what are objectives um and strategies that we can set-up to make sure that patients are living better? So, I think the treatments are basically set-up to basically help you achieve those two goals. What can we do to help you live longer and feel better?

Katherine Banwell:    

Yeah. Well, let’s walk through the types of treatments that are used today to treat advanced prostate cancer. What are the treatment causes and who are they appropriate for? Let’s start with surgery, for instance.

Dr. Rana McKay:       

So, surgery is something that’s utilized uh, early on when people are diagnosed with cancer. It tends to be utilized when the cancer has not necessarily spread to other parts of the body but is still localized within the prostate itself or maybe there’s just some little bit of breakthrough in the capsule. Sometimes it can be used in people who have involvement of the prostate cancer in the lymph nodes. But it’s generally not utilized in people who have cancer that’s spread to other parts of the body.

Katherine Banwell:    

Mm-hmm. What about other treatment classes? What are they?

Dr. Rana McKay: 

So, radiation can also be utilized. Radiation is a treatment modality that can be used for people with localized disease and um, also it can be utilized for people with advanced disease to treat the primary tumor.

Additionally radiation therapy can be used to help treat symptoms um, if there’s a bone lesion causing pain or other areas that are causing discomfort. Sometimes radiation to those areas um, can um, mitigate pain. When I think about the treatment classes for prostate cancer um, they generally break down into several categories. The first um, um, most predominant category is the hormonal therapy category. Hormonal therapies are really the backbone of treatment for men with prostate cancer and they include the more traditional hormonal therapies that really work to just drop testosterone. So, just LRH – L – LRHA agonists and antagonists and also, they include um, newer hormonal therapies in the form of pills that really target um, strategies at also affecting testosterone function and testosterone production. Another class is also the chemotherapy agents. There are two FDA approved chemotherapies for prostate cancer that are life prolonging and um, uh there’s a certain role for uh, chemotherapy for people with advanced disease.

There’s also immunotherapy that can be utilized. Um, there’s a um, uh, vaccine therapy that’s actually one of the first uh, FDA vaccines for any solid tumor that’s proving in prostate cancer that can be utilized. There’s also radio pharmaceuticals.

So, these are specific agents that deliver um, a bits of radiation to specific areas. Whether it be radium 223 which targets the bone or the newest radio pharmaceutical, which was approved called uh, lutecium PSMA that um, basically delivers beta-radiation to little – sites of PSMA expressing cancer cells and the last category that I would highlight is the category of targeted therapy. There are uh, two targeted therapies for prostate cancer for patients who have like genomic alterations. Those include the drugs olaparib and rucaparib. So, as you can see there’s a wide spectrum of drugs that can be utilized to really keep this disease at bay.  

Katherine Banwell:    

Dr. McKay, for these treatment classes, what can patients expect as far as side effects?

Dr. Rana McKay:       

Absolutely. So, I think side effects – discussing side effects is a really important part of the discussion for selecting any one given therapy and in general, I think um, when we talk about the hormonal therapies one of the side effects that people can get is largely fatigue.

But a lot of the symptoms are related to low testosterone. And so, that may mean muscle loss, bone loss, um, you know, uh, hot flashes, um, fatigue, decrease libido, um… So, you those are things to consider with hormonal therapies. With the chemotherapies, I think the big ones we worry about are fatigue, risk of infection, um blood counts dropping a little bit, people getting tired, numbness and tingling in the hands and feet can occur, some swelling in the legs are common side effects for chemotherapy agents. With regards to the um, uh, immunotherapy with the vaccine therapy, it actually tends to be a fairly well tolerated treatment. Maybe some fatigue, rarely some dizziness or some lip – lip sensitivity, numbness with the – the process of kind of collecting the cells. But it actually tends to be fairly well tolerated.

The um, targeted therapies can cause fatigue. They can cause the blood counts to drop and can impact bone marrow function. There can be sometimes GI side effects. Nausea, um, rash, um and then the immune therapy, the pembrolizumab, that is FDA approved sometimes that can cause immune related adverse events which is kind of over activation of the immune system developing you know, what I’d call it as the itises. Colitis or pneumonitis which is inflammation of various organs and symptoms related to wherever that may be.

Katherine Banwell:    

When should a patient consider a clinical trial as a treatment option?

Dr. Rana McKay:        

So, I generally think that a patient should consider a clinical trial at almost every juncture that a – a clinical decision is being made. I think sometimes there’s this misperception that, “Oh. Clinical trials should only be utilized when I don’t have any other options.” Where in fact I would say clinical trials should be an option to discuss every single time a treatment is being changed. Um, because you know the ultimately the goal is to make sure patients are as I said, living longer and living better and um, you know, making sure that clinical trials are an option on the table at every juncture is really a key step in that process.

Katherine Banwell:    

What are the benefits of being part of a clinical trial?

Dr. Rana McKay:       

So, I think there’s a lot of benefits. I think um, you know, uh for patients with advanced disease it may provide access to drugs that they otherwise not necessarily have access to.

Um, so the standard of care therapies you know, we can prescribe those at any juncture. They’re standard of care. But clinical trials um, really offer an opportunity to experiment with a uh, uh another agent um, and doesn’t necessarily take away from the standard of care options.

I think um, the other thing is you know, I think a lot of patients with advanced prostate cancer, they um, they – want to give back to the community. They want to leave a legacy. They want to contribute to the science. They wanna be a part of that mission to make tomorrow better than today for men with prostate cancer and I think participating in clinical trials can really help achieve that goal. Um, and also benefit the individual as well.

Katherine Banwell:    

What about emerging treatments? Are there any that patients should know about?

Dr. Rana McKay:       

Absolutely. So, there’s a lot of treatments that I think are currently undergoing extensive testing.

There’s um, additional uh, targeted therapies um, for example CDK46 inhibitors that are being tested broadly in the um, um hormone resistant space and the newly diagnosed setting. Um, there’s um, also AKT inhibitors. There are other targeted therapies that are being tested. There’s novel hormonal treatments that target resistant pathways like the antigen receptor degraders. There’s a slew of immunotherapy options um, cell therapy, bi-specific antibodies that are also being tested. So, there’s a lot of really exciting and novel treatments that are looking at overcoming resistance for people with advanced disease.

Katherine Banwell:    

Hm. Do you recommend that men with advanced prostate cancer get the COVID vaccines and the boosters?

Dr. Rana McKay:       

Very good question and in general, I do recommend the vaccines. Especially for patients with advanced disease and those that are on therapy. Um, several studies have demonstrated that patients with cancer are at increased risk of having complications related to COVID and particularly patients that are on active treatment with cancer are at even greater riskSo, um, I would definitely recommend vaccination as a preventative strategy to prevent really complications related to COVID.

Katherine Banwell:    

Mm-hmm. Thanks, Dr. McKay. That’s helpful information. Since prostate cancer affects men differently. Let’s review what factors could impact which treatment is right for their individual disease. How about we start with symptoms?

Dr. Rana McKay: 

So, yeah. I mean absolutely. I think symptoms are definitely something that plays into effect.

Um, sometimes when patients are first diagnosed, they may not have symptoms. But, you know, boney pain. Um, Symptoms of urinary obstruction. You know, there’s specific um, uh, treatments and uh, strategies that we can deploy to help with those kinds of things. Um, you know other factors that I think I – we take into account when we’re making decisions about which agent should any one patient receive is where are there sites of metastases? Um, is there disease just in the bones and lymph nodes or are there other organs involved? Um, what’s the genomic make-up of the tumor? Um, there are certain treatments that we would utilize if someone had a certain specific you know, uh genetic make-up for their tumor. You know, other things that are really important are what kind of drugs has the patient seen before or has that tumor been exposed to? Because that also helps us strategize for what to give them in the future.

Katherine Banwell:    

Do you take into consideration the patient’s comorbidities and their age and overall health? Things like that? 

Dr. Rana McKay: 

Absolutely. Yeah. I think we need to absolute take that in account. I think – I think age is one thing. But I think functional status is um, just as – as important as the actual number itself because people are very different regarding um,  the things that they can do at various uh, age limits and so, that absolutely takes into account weighing the side effects of any given therapy and how that may interact with someone’s existing comorbidities and it may be something that we have to work with a team of other doctors to basically make sure that there is comprehensive, well-rounded care for any one patient.

For example, some therapies may increase the risk of hyper-tension or increase the risk of volume overload and so, if somebody has issues with that already we may have them see a cardiologist so we can make sure that um, you know, we’re kind of addressing the totality of the patient experience. 

Katherine Banwell:    

What do you mean by volume overload?

Dr. Rana McKay: 

Uh, volume overload I mean if they’ve got too much fluid on board. So, maybe if they have heart failure or something like that and we have a therapy that’s gonna cause them to retain fluid. And so then, we would have to work with a cardiologist to make sure that they don’t run into issues.

Katherine Banwell:    

Right. That makes sense. What are the common symptoms of advanced prostate cancer?

Dr. Rana McKay: 

So, um, you know, I would probably say there common symptoms and just because somebody has these symptoms doesn’t mean they have prostate cancer. But fatigue, weight loss, urinary symptoms, trouble urinating, you know, benign prostatic atrophy is one of the most common symptoms or most common conditions in men and um –

Katherine Banwell:    

What does that mean?

Dr. Rana McKay: 

Um, so sort of benign enlargement of the prostate. Um, you know that’s a common phenomenon that happens with age and it can affect somebody’s ability to urinate.

Um, but um you know uh, sometimes with prostate cancer it can also impact somebody’s ability to urinate. Their stream, their flow. Um, they may have rectal discomfort. They may feel tired, boney pains. Usually, I tell patients you know persistent progressive symptoms that are just you know not going away, not getting better. Those need to be looked at by a physician to evaluate further. 

Katherine Banwell:    

Mm-hmm. You mentioned genetic mutations. Should patients advocate for genetic testing if they haven’t had it already?

Dr. Rana McKay: 

Um, it all depends on uh, what kind of uh, where they are in the process. So, for most men who have advanced disease, they should undergo genetic testing of both their tumor, and it is also recommended to do hereditary testing for patients who have advanced disease. Um, and that information may not necessarily be utilized at the exact time that the test is done.

But it may be utilized down the road for treatment options at a later time point. Um…

Katherine Banwell:    

Mm-hmm. Once a man is undergoing treatment for advanced prostate cancer how are they monitored to see if it’s actually working?

Dr. Rana McKay: 

So, a lot of ways. So, one is by just you know, visiting with the patient. Making sure that their symptoms are in check. Making sure that they’re not developing new um, aches or pains that are worrisome. It’s by checking their labs um, in addition to their organ and bone marrow function. We would check their PSA. Um, and PSA isn’t the whole story. But it is one factor that contributes to us determining whether treatment may or may not be working. It’s also doing intermittent scannings. So, um, you know, uh, CT scans of the organs, of the lymph nodes. Bone scan and now we actually have PSMA based imaging which can be integrated to help um, assess uh, where the disease is and um, not yet being utilized to assess whether something is working because we haven’t really defined the criteria there.

But um, it can be utilized as well.

Katherine Banwell:    

Mm-hmm. Dr. McKay, how would you define precision or personalized medicine and how close are we getting to personalized medicine for advanced prostate cancer?

Dr. Rana McKay: 

Yeah. So, what I – how I define it is the right treatment for the right patient at the right time. It’s basically you know, based off of somebody’s genomic profile of their tumor and ideally that genomic profiling is done close to the time that that treatment is being initiated. So, within six months or twelve months of somebody starting a given therapy we understand the genetic make-up of the tumor. The tumor has you know, for example a BRCA1 alteration and we know that olaparib is a drug that can be utilized and has demonstrated efficacy for people that have that mutation and then we would use that agent. So, it’s basically trying to um, personalize therapy based on the genomic information of that tumor.

And um, I think we are getting there. There are actually trials now that are being launched that are bio-marker driven trials with bio-marker selected therapies for patients based on -off of not just DNA but also RNA to help with um, allocating a given therapy.   

Katherine Banwell:    

What do you feel are the common obstacles to care for a man with advanced prostate cancer?

Dr. Rana McKay: 

So, I think that there can be a lot of obstacles with regards to um, you know, comprehensiveness of the care. You know it’s one thing to sort of, “Okay. This is the next therapy to treat you with.” But there’s a lot of side effects that can happen with any one given therapy and ensuring that there is open dialogue between um, uh a man and his – his clinician and caregivers.

You know, I think that that can sometimes be a hurdle. Like that open communication can be so important. It’s not just about picking the next best drug but it’s ensuring that there’s sort of comprehensiveness in care. I think a lot of um, you know, patients they may not necessarily know and they’re really kind of dependent on their clinician to sort of go through the compendia of options that may be available and why one may be better than the other for any one given scenario. So, I think it’s like that shared decision-making, that open dialogue.

Um, you know, I think also thinking about advocacy networks, I think um, you know, I can say things until I’m blue in the face like this is what being on ADT feels like. But I think sometimes actually connecting with another patient whose gone through the same experience who can kind of weigh in from the patient perspective like what it actually feels like, I think is not to say a hurdle. But I think we can do a better job as a medical community of making those networking connections available for patients so they can be a part of a broader community of individuals like them going through the same thing they’re going through.

Katherine Banwell:    

Yeah. It helps to know that there are others going through exactly what you’re going through or similar symptoms. We received a patient question prior to the program. What is the difference between my PSA level and Gleason score?     

Dr. Rana McKay: 

Yeah. So, very good question. So, Gleason score is something that is determined based off a pathologic assessment. So, it’s basically you know, a biopsy is done from the prostate or the – the surgical specimen from the removal of the prostate is looked at under the microscope and a Gleason score is based off what something looks like underneath a microscope and ideally, a Gleason score is given really only for the prostate – for tissue derived from the prostate.

So, if somebody has a bone biopsy for example or a lymph node biopsy, they’re not going to necessarily get a glycine score per se. It’s been – been validated from the prostate itself and ideally, also, an untreated prostate. So, if somebody has you know had radiation therapy and then has a biopsy, the Gleason score there is – there should not necessarily be a notation of what a Gleason score is. It’s really an untreated prostate. Now PSA is prostate specific antigen and it’s a protein that’s made from the prostate gland and it’s found in circulation. PSA doesn’t hurt any – the actual you know, molecule itself is – is innocuous. It doesn’t hurt anything. It’s just a marker of um, sometimes can be a marker of burden of disease in prostate cancer and I think sometimes we as clinicians do you know, you know a disservice to some patients because I think we fixate – we can fixate a lot on PSA.

But PSA is not the whole story and it’s one factor of several factors that we take into account in determining whether someone needs treatment or whether a treatment is working or not working.

Katherine Banwell:    

Why should patients feel confident using their voice in partnering in their care? Do you have any advice?

Dr. Rana McKay: 

Um, I mean it’s – it’s absolutely important for patients to share their perspective and for there to be shared decision making at every single juncture along the way. Even around decisions to not treat. So, you know, I think it’s a lot of um – there’s a lot of grays in prostate cancer and a lot of art in deciding what treatment to do and at what specific time and for any given patient given the values that that patient brings to the table, they may come back with a different decision compared to another patient. So, without the patient you know voicing what their values are it’s impossible to make a treatment decision.

So, it is so critically important to have that open communication with your clinician.

Katherine Banwell:    

So, in addition to that – in conjunction with that, should men diagnosed with advanced prostate cancer consider a second opinion or consulting with a specialist?

Dr. Rana McKay: 

I think it’s always a great idea to get a second opinion. Um, you know, I think that um, you know, it will only empower individuals um, when they seek sort of a second opinion to either confirm um what their physician has already told them and then they have reassurance that they’re on the right path or maybe provide some new um, novel insights that they can take into consideration and just think about how that could be applied to them. So, you know, I think that a second opinion is always really valuable.

I will balance that by saying um, sometimes it can be detrimental if there’s lots of opinions because I will say that coming to a consensus when there’s lots of different specialists that are involved, and everybody makes the soup a little bit differently –

Katherine Banwell:    

Yeah.

Dr. Rana McKay: 

Sometimes that I think that can actually um, hurt patients in being able to actually come to a decision because then they’re like, “I don’t know what decision to make. This person said do this. This person said do that. This person said do that.” Um, and so that can sometimes be um, detrimental. But a second opinion, I do always encourage it. I do always value it. But I always want the patient to bring it back to me so I can share with them and discuss, “Okay. I understand. This is why x said X-Y-Z. This still aligns. This still doesn’t.” They need a quarterback like you know, it’s one thing to sort of get second opinions. But I think every man with prostate cancer should have a quarterback that’s driving their care and advocating for them.

Katherine Banwell:    

Yeah. How can patients find specialists near them?

Dr. Rana McKay: 

So, um, I will say that they are national comprehensive cancer institutes. They’re all across the country in rural areas and not. I think um, you know finding the closest NCI designated comprehensive cancer center close to you is probably a good place to start and identifying who is seeing um patients with genetic urinary malignancies or prostate cancer at that facility is a good place. I think the prostate cancer foundation is an excellent advocacy group for patients with prostate cancer. They have a tremendous amount of resources um, to help connect patients with um, clinicians, and other resources um, in their journey with cancer.

Katherine Banwell:    

How can caregivers best support their loved ones?

Dr. Rana McKay: 

So, I think being present is one of the first things. Um, you know, I think that uh, um, you know, uh, being you know, supportive, being present.

Like you know, attending the doctor – doctor’s visits. It doesn’t necessarily have to be every single doctor visit. But those critical doctor visits where um, you know clinical decisions are being made. I think it’s really important also um, to there may be some hesitancy on the part of patients to sometimes be open or vocal with their clinicians about various aspects of what they may be experiencing at home, or they may be undermining or sort of – I think caregivers can help in sort of giving an outsider’s perspective. “Well, this is how things are going at home,” and “You know this is how things are,” and “These are the things that we value and we’re gonna go on this family trip,” and “This is a big-ticket item for us. So, how can we work around planning a treatment plan that allows us to do that?” So, I think it’s really important.

Katherine Banwell:    

ASCO was held in June. Is there news from the conference that patients should know about?

Dr. Rana McKay:        

Yeah. So, I think some of the biggest therapies in prostate cancer that was one of the newest therapies that was just FDA approved is um, Lutetium PSMA. It’s um, a radioligand therapy that targets specifically PSMA expressing cells. Um It delivers a little bit of beta radiation to those cells. Um, that therapy was approved this past Spring and there highlights at ASCO about the utility of this therapy. Um, and again, there’s a series of novel compounds that are being tested in prostate cancer not yet ready for prime time but a lot of exciting work that’s being done um, to try to get new drugs that work better for our patients.

Katherine Banwell:    

Mm-hmm. Going back to ASCO and new developments, how can patients stay informed about research developments like – like these that happen at ASCO.

Dr. Rana McKay:

So, very – very good. I think there’s a lot of networks for people with prostate cancer. I think one like I mentioned, the prostate cancer foundation it’s a wonderful community. Um, that really focuses on making sure that up to date, you know, uh, evidence-based data is uh, distributed to patients in a manner that is – that makes sense. That’s there’s not a lot of medical jargon and so I think that the PCF is really a wonderful resource. Uh, ASCO itself also has um, you know patient interfacing you know, materials through their website.

American Cancer Society does as well. Um, the American Cancer Society can also be a wonderful resource for patients that are newly diagnosed or going through treatment.

Katherine Banwell:    

Mm. Before we end the program, Dr. McKay, I wanted to ask. Are you hopeful that men can thrive with advanced prostate cancer?

Dr. Rana McKay:       

Oh, I am absolutely hopeful that they can thrive. I mean that is um, the name of the game and I think there’s a lot of um, uh, people who can look to for motivation.

Um, uh, to basically show that despite treatment, despite having advanced disease patients can thrive and continue doing all of the things that they love that give them joy and satisfaction in their lives.

Katherine Banwell:    

It seems like there’s a lot of progress and hope in the field which is good. Dr. McKay thank you so much for taking the time to join us today.

Dr. Rana McKay:       

Of course. My pleasure.

Katherine Banwell:    

And thank you to all of our partners. To learn more about prostate cancer and to get tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks so much for joining us today.

How to Play an Active Role in Your Prostate Cancer Treatment and Care Decisions

How to Play an Active Role in Your Prostate Cancer Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

What steps can you take to engage in your prostate cancer treatment and care decisions? Dr. Atish Choudhury discusses current and emerging prostate cancer therapies, reviews key treatment decision-making factors, and shares advice for self-advocacy.

Dr. Atish Choudhury is the Co-Director of the Prostate Cancer Center at Dana-Farber/Brigham & Women’s Cancer Center.
Learn more about Dr. Choudhury here.

Download Guide

See More from Engage Prostate Cancer

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Using Your Voice to Partner in Your Prostate Cancer Treatment Decisions


Transcript:

Katherine:                  

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today, we’re going to explore the goals of advanced prostate cancer treatment and discuss tools for playing an active role in your care decisions.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Joining us today is Dr. Atish Choudhury. Dr. Choudhury, welcome. Would you please introduce yourself?

Dr. Choudhury:        

Hello. Thank you so much for the invitation. So, I’m a medical oncologist at Dana-Farber Cancer Institute, and I’m the codirector of the prostate cancer center at the Dana-Farber/Brigham and Women’s Cancer Center. And I serve as the chair of the Lank Center for Translational Research as well, and ’t’s my pleasure to be here.

Katherine:                  

Thank you so much for taking the time out of your schedule to join us. Today, we’re talking about advanced prostate cancer.

What exactly does “advanced” mean in terms of this cancer?

Dr. Choudhury:          

Yeah. So, it’s actually a pretty broad term, and it can mean different things in different contexts. But generally, what it means is that it’s cancer that has extended outside of the confines of the boundaries of the prostate itself – either locally where it is into the surrounding fat around the prostate capsule or to local lymph nodes, where it could also spread to other parts of the body – like lymph nodes, bone, and other organs.

So, it can really mean different things depending on the context.

Katherine:                  

Before we get into the types of treatment available, let’s start by understanding the goals of treatment. What are the goals of advanced stage prostate cancer?

Dr. Choudhury:              

So, in general, the goal of treating any cancer is to a live a long, happy, healthy life with limited quality of life troubles from the cancer itself or its treatments. And so, for localized prostate cancer, that generally means treating with curative intent – that we give radiation or surgery, potentially in combination with hormonal treatments so that the cancer is taken care of and people can be cured and not need further treatments moving forward at all.

And there are situations, even in fairly advanced cases, where that’s a reasonable and accomplishable goal. And there are other situations that we might not be able to cure the cancer completely, but the treatments can be quite effective at keeping it under control and keep people with a very good quality of life so that prostate cancer is not a day-to-day burden for them and that they can survive with cancer for years, and years, and years.

Katherine:                  

It sounds like these goals would be determined with members of your healthcare team. So, who is typically on a patient’s prostate cancer healthcare team?

Dr. Choudhury:            

Yeah. So, generally, the consultations here at Dana-Farber are multidisciplinary, with a medical oncologist, a radiation oncologist, and a urologic oncologist – so, a surgeon.

And so, if a patient is a good candidate for treatment to the prostate itself, then certainly, the surgeon and the radiation oncologist will talk about those treatments. And if the treatment is primarily with medications, then the medical oncologist will generally sort of take the lead. But there is often a role for local treatment to the prostate itself, even in cancer that’s spread beyond the prostate. So, that’s why the multidisciplinary consultation is so important.

Katherine:                  

Right. What do you feel is the patient’s role as a team member?

Dr. Choudhury:           

Absolutely. So, I think it is very important for the patient to make sure that they come into these multidisciplinary meetings with questions around “What is my stage?” “What are the choices?” “What do I expect with treatment? Without treatment? With the various treatment options?” And basically, to take in the advice that they’re getting from the different members of the multidisciplinary team, and really think about how that’s impactful for them and their goals for themselves and what they really hope for the short term and for the long term.

I think what gets tricky is that there’s really very not-great sources of information that’s out there online and in YouTube videos and things like that, and I think it does play an important role for the patient to really understand what are the real high-quality sources of information – they tend to come from academic medical centers like ours. And certainly, we do encourage second opinions at other high-quality, high-volume centers so that the patients understand that the recommendations that are being made are generally made based on the based data and with people with a lot of experience at treating their kind of cancer.

Katherine:                  

What about caregivers? How do they fit into the team?

Dr. Choudhury:             

Caregivers are critical because patients are not always the most expressive at, really, what their wants, and needs, and desires are. And especially when they’re on treatment, sometimes they’re not so expressive around the things that are bothering them on a day-to-day basis.

So, the caregivers are really important for communication with us to be kind of another set of eyes and ears in terms of kind of reporting what the patient’s symptoms are or what their goals or desires are that maybe they themselves don’t feel comfortable expressing. But they also play an important role in helping us with, kind of, lifestyle recommendations to the patient. Because certainly, much of the process of doing well with prostate cancer treatments is kind of lifestyle modifications – makes sure you’re eating healthy, exercising regularly – and the caregivers can play a very important role in making sure that patients stick to that kind of regimen as well.    

Katherine:                  

I would think one of the issues for a patient too is that just having a cancer can be overwhelming and can make it difficult for them to even remember all the questions and concerns that they have.

Dr. Choudhury:            

Yeah, that’s absolutely critical, and the caregivers play a very important role. So, often, people who are not partnered, for example, will just bring a friend to these appointments just to be that second set of eyes and ears.

Katherine:                  

Dr. Choudhury, we received this question from an audience member prior to the program: What is palliative care?

Dr. Choudhury:           

So, palliative care is really a branch of medicine that helps with symptom management. And so, that symptom management doesn’t necessarily have to be end-of-life sort of symptoms relating to death and dying. It can be just along the way to help with managing the symptoms related to cancer and its treatment, but also to be kind of another medical provider to help with communication of goals of care – what’s really bothersome, what’s really important – so that we kind of incorporate those wishes and desires into the management decisions that we make.

So, a patient does not have to be at end-of-life to engage with palliative care. Certainly, even earlier engagement with palliative care can be helpful to maximize quality of life along the treatment journey. But as symptoms become more bothersome, certainly, our palliative care colleagues can be incredibly helpful – not just in helping manage pain, but also nausea, also depression and psychological side effects. So, they’re a really critical part of our treatment team.

Katherine:                  

Yeah. I think we have a pretty good understanding and the goals of treatment. So, let’s walk through the types of therapy that are used today to treat prostate cancer.

If you would start with surgery?

Dr. Choudhury:            

Sure. So, surgery is a radical prostatectomy, and they take out the prostate – they take out neighboring structures called seminal vesicles, they take out the surrounding fat, and they’ll usually take out some neighboring lymph nodes as well. And there are advantages of surgery in that when the prostate is out, the pathologist can examine the whole prostate front to back, side to side, as well as those neighboring structures to really understand the stage of the cancer – “Where is it?” – and also, the grade – “Is it a high-grade cancer, a low-grade cancer, somewhere in the middle?”

And it really helps guide “What is the risk of developing recurrence afterwards, and are there further treatments that we should be giving after the surgery? For example, radiation to the prostate bed to decrease the risk of recurrences. Surgery does have its own set of potential side effects and complications, so it’s not appropriate for everyone, but in general, that’s the process.

Katherine:                  

What other treatment options? You mentioned radiation. What else is there?         

Dr. Choudhury:          

Yeah, so, radiation comes in two forms: there’s seed radiation, which is implantable little radioactive pellets that are implanted throughout the prostate. And then, there’s external radiation, and that can be given in several forms and over several schedules that it’s really important to discuss with the care team.

The other forms of treatment that people on this call might’ve heard about or read about are in a category called “focal treatments,” and these are basically ways to – and the term we use is a blade but zap – an area of the prostate using lasers, or high-intensity ultrasound, or with freezing an area of the prostate, or with something called “irreversible electroporation.”

These are basically all ways to, again, zap an area of the prostate either with heat or with cold with the intention of killing off cancer cells in an area. And the trouble is that none of these treatments have actually been demonstrated to improve outcomes related to prostate cancer compared to just surveillance alone. And it does complicate, sort of, the monitoring afterwards to see if something has come back.

But there might be very selected patients where there’s an area of cancer that’s seen on a scan – like an MRI – with no cancer seen outside of that area who might decide to pursue this possibility of focal treatment with the goal of maybe putting off the need for something like radiation or surgery. But that’s something that really should be discussed with a multidisciplinary team so that people really understand what they’re getting into in terms of risks and potential benefits.

So, those treatments are not really considered standard at this time.

Katherine:                  

What about hormonal therapy?        

Dr. Choudhury:   

Yeah, so, hormonal therapy plays a role in the treatment of prostate cancer, really depending on the stage and the other treatments that are being considered. So, for example, if a patient is going to surgery for a localized prostate cancer, in general, we wouldn’t use hormonal treatment either before or after the surgery unless they’re planned for radiation after the surgery.

However, for patients who have intermediate risk or higher localized prostate cancer and are getting radiation, then we will often recommend hormonal treatments, which are basically testosterone-lowering drugs, to make the radiation work as well as possible. And then, for patients who have advanced cancer beyond where surgery or radiation is going to be of help, then, hormonal treatments are important to treat the cancer wherever it is.

And that’s because prostate cancer cells, wherever they are in the body – wherever they’re in the prostate itself, or in lymph nodes, or bones, or other organs – depend on the testosterone in your body to supply a fuel – to support its growth and survival.

And so, lowering the level of testosterone in the body basically deprives the cancer cells of that fuel and starts a process of killing cancer cells even without any need for radiation, or chemotherapy, or things like that. However, hormonal treatments are not curative. They don’t kill all the cancer – they kill some and put the rest to sleep. And so, if you stop the hormonal treatment, the cancer will grow back, and that’s why it’s not a treatment on its own for localized prostate cancer.

And that’s also why, for prostate cancer that’s spread, we often add on additional medications to the testosterone-lowering drugs to be more effective at really killing the cancer wherever it is compared to the testosterone suppression alone.

Katherine:                  

Oh, I see. For advanced disease, what treatments are available for patients that are hormone-sensitive or -resistant?

Dr. Choudhury:           

Yeah, so “hormone-sensitive” means that the cancer has advanced, but the patient hasn’t started on testosterone-lowering drugs yet. And so, as I had mentioned, testosterone lowering is really the backbone of treatment of these patients. And so, there are additional treatments that have been demonstrated previously to be effective after testosterone-lowering by itself stops working, and these include a chemotherapy drug called docetaxel. And in addition, there are more potent hormonal drugs called abiraterone, enzalutamide, apalutamide, and darolutamide.

And the role of these other drugs is to block hormonal signaling within the cancer cells from hormones other than testosterone. And so, by doing the more potent hormonal drug in conjunction with the testosterone lowering, that leads to a much deeper response – much more tumor shrinkage – and, it turns out, also prolonged survival in patients treated with those combination treatments – compared top people who are treated with testosterone lowering alone and then receive these drugs later.

So, there’s something about treating more aggressively at the beginning in this hormone-sensitive state that plays out in prolongation of survival. And not only prolonged survival, but improved quality of life due to delaying the symptoms of cancer grown and progression.

Katherine:                  

Right.        

Dr. Choudhury:   

When we then talk about castration resistant disease, certainly we use the same classes of drugs, but then, there’s a wider armamentarium of things that we use that include, again, other kinds of chemotherapy.

There are radiation drugs, and an approved drug Radium-223. And there’s another drug on the horizon called Lutetium PSMA. There are immune therapy drugs – something called Sipuleucel-T – and then, this is also a situation where we do genetic testing of the cancer to understand if there’re certain –what we call “therapeutic vulnerabilities.”

Other treatment options that are available based on the genetics of the cancer that might be helpful in some people? And specific options include a chemo-immune therapy called “Keytruda” in a small subset of patients with particular genetic changes involving genes involved in mismatched repair of DNA. And then, there’s another set of targeted treatments called “PARP inhibitors” for certain sets of patients who have alterations in genes involved in homologous recombination repair of DNA.

So, that’s all very complicated, and so that’s why it’s important to get treated with high-volume providers of prostate cancer patients so that they’re really aware and onboard with these various treatment options that are available.

Katherine:                  

Yeah. Where do clinical trials fit in?

Dr. Choudhury:       

So, clinical trials can fit in anywhere along the treatment trajectory for prostate cancer. It’s not something that’s reserved for kind of late-stage disease. So, for example, for people with localized disease, there are different types of treatment strategies that might be available to maybe enhance the activity of the surgery or the radiation that’s planned. And so, we might consider a clinical trial even for localized prostate cancer.

And then, anywhere along the way, there are standard treatments that are available, and then, there are some experimental approaches that might be available. And the experimental approaches might be to add an additional drug to the standard or to actually – what we call “deescalate treatment” – give a little bit less of the medication and see if the outcomes are the same. And these are tests.

And so, the control arm, when there’s a randomized trial, is generally considered a standard of care. And then, the experimental arm is some alteration or deviation from that standard. But many of our trials are also single-arm trials where we’re testing some experimental regimen that all patients who participate in the trial will take part in, and it’s really important for the patient to ask, “What are the clinical trials available?” “What are the alternatives as far as standard treatments?” and “Are there other clinical trials other than the one that’s being discussed,” that might be appropriate for them?

Katherine:                  

Are there emerging approaches that patients should know about?   

Dr. Choudhury:        

Yeah. So, a lot of the emerging approaches are related to the genetics of the prostate cancer, as I just mentioned. And then, these different forms of radiation drugs – in addition to the ones that have already demonstrated survival advantage, there are other ones in the pipeline. And then, one thing that patients are very curious about is immune therapy approaches to prostate cancer.

Now, the standard kind of immune therapy drugs that are approved for lung cancer, and melanoma, and kidney cancers don’t tend to work particular well for prostate cancer. But there are many clinical trials trying to combine those kinds of drugs with other drugs or have newer approaches to immune therapies that patients with advanced cancer can certainly ask about.

Again, all of this is really experimental, and people need to understand that these sorts of approaches aren’t going to help everyone. But participating in a clinical trial allows our patients to contribute to knowledge that can be useful for other patients down the line.

Katherine:                  

Right. Now that we’ve delved into the types of treatment, let’s talk about what goes into deciding on an approach. What do you typically consider when determining the best treatment approach or option for a patient?

Dr. Choudhury:   

So, the starting point and the ending point is the patient themselves. And so, “the patient” means “What is their age? What is their fitness level? What are their activities? What’s the overall life expectancy? What are there other medical issues?” And then, we consider the cancer – “What is the stage? What is the grade? Where has it spread to, if it’s spread?”

And then, we try to incorporate all of those pieces with data – with clinical trials that have already been reported – and we have a lot of data in prostate cancer from patients who’ve participated in clinical trials, often randomized to one approach versus another, that gives us a sense of “What are the approaches that really benefit patients in terms of increasing likelihood of cure or prolonging the survival?”

And so, once we incorporate all of those things, we can come up with some treatment suggestions, and then patient preference on those suggestions obviously plays a very important role. But sometimes, we start down a line, and the patient is having troublesome side effects or it’s not working as well as we’d really hoped, and it’s important to be adaptive and to change things if things are not going down a route that we’d really hoped. So, that’s an ongoing conversation. It’s not that you make a treatment plan at the first visit and that’s the plan that’s stuck with throughout the whole course of things.

It’s a conversation at every visit on how things are going in terms of how the patients are doing and how the cancer is responding. And then, again, try to manage side effects as well as we can and adjust things if we need to along the way – and maybe switch to something that’s potentially going to be better tolerated or more effective, depending on what we see.

Katherine:                  

Right. It sounds like there are many factors to weigh when making this decision. I’d like to address a list of common concerns about treatment that we’ve heard from the community. So, I’d love to get your take on these. “There’s nothing that can be done about advanced prostate cancer.” Is that true?

Dr. Choudhury:           

So, that is very much untrue in that even patients with pretty advanced prostate cancer – even what we call “high-volume” kinds of prostate cancer – can live for years, and years, and years with appropriate treatments.

And the concern, oftentimes, is that the way that we get those years, and years, and years are with treatments that lower levels of testosterone, and I’m guessing that some of your questions coming up are related to concerns around side effects of treatment. But many of our patients tolerate those side effects pretty well and can live quite a good, and vigorous, and fulfilling life even with pretty advanced prostate cancer.

Katherine:                  

The next one: “Clinical trials are a last-resort treatment option.”

Dr. Choudhury:   

Yeah, so, as I’d mentioned before, clinical trials can be appropriate anywhere along the treatment trajectory of prostate cancer, and they are often being compared against standards which are often pretty good, but can we make them better? And certainly, participating in clinical trials isn’t for everyone, but for a long of our patients who are interested in seeing if an experimental approach might be beneficial to them or contributing some knowledge to patients down the line really do find trial participation to be quite fulfilling.

Katherine:                  

All right. The next one is: “Prostate cancer isn’t genetic, so I don’t need to be tested.” Is that the case?

Dr. Choudhury:        

No. So, it turns out that prostate cancer is actually one of our most heritable cancers. Somewhere between 40% and 50% of the predisposition to prostate cancer is actually genetic, or inherited based on family. So, the part that’s tricky and the part that is hard to maybe explain to patients is that a lot of that heritability is not encompassed in particular cancer genes in the way that many people are familiar with with breast and ovarian cancers, which are often linked to genes called “BRCA-1” and “BRCA-2.” So, a small subset of patients with prostate cancer do have alterations in that BRCA-2 gene, or BRCA-1, or ATM, or some other genes involved in breast and ovarian cancers.

And that does impact, potentially, their treatments down the line, and certainly is impactful for themselves, their siblings, their children as far as, potentially, screening recommendations for other cancers. But oftentimes, we’ll do one of these tests in patients who have a pretty extensive family history of prostate cancer, and they come out negative, and the patient is very confused because they clearly have a family history, but it’s because not all the risk of prostate cancer is actually encompassed in these gene tests that we run.

Katherine:                  

Ah, okay. The next concern is “I’ll lose all sexual function when I receive treatment.”

Dr. Choudhury:         

So, it very much depends exactly what the treatment is, and what’s being offered, and what the recovery is like.

So, for example, for patients who go into a prostatectomy and have very good erectile function, it’s not inevitable that you’ll lose your sexual functioning after a prostatectomy. There is a process – we kind of refer to it as “penile rehab” – of using medications like a Viagra or Sialis to restore the blood flow. You could use certain things like vacuum pump devices to restore the blood flow, and again, it’s not inevitable that people are going to lose their sexual functioning after a prostatectomy.

Even with testosterone suppression, while it plays a role in libido and erectile function, it’s not inevitable that people lose their libido and erectile function completely, even on these drugs. But certainly, more often than not, people will lose their erectile function on testosterone-lowering medications.

And so, there are alternative ways to get erections – involving, again, use of vacuum pump devices or injections that people can give themselves into the penis. People can have penile implant surgery to be able to get erections that way. And so, it’s really dependent on what the situation is.

Again, none of those more mechanical interventions are really ideal, but particularly when people have a defined course of treatment – for example, a surgery or radiation with a brief course of hormones – people can recover erectile function even after those sorts of interventions. And if they can’t, then we do have other approaches that will allow people to still be able to be sexually intimate with their partner after all of the treatments are completed.

Katherine:                  

Dr. Choudhury, one more concern: “My symptoms and side effects can’t be managed.”

Dr. Choudhury:           

Yeah. So, again, it’s very rare that we run into situations where there are side effects or symptoms that can’t be managed at all, in the sense that we have very effective medications against hot flashes, or moodiness, or pain, or –just fatigue. And certainly, lifestyle plays a big role in this. Also, a lot of the symptoms that people express are related to underlying depression and anxiety issues, and certainly, engaging with a mental health provider can be helpful in terms of managing those as well.

And then, there’s a lot of nonpharmacologic treatments – meaning nonmedication approaches that can provide people a lot of benefit in terms of their quality of life, and we have an integrative center called the Zakim Center for Integrative Medicine that helps with the relaxation techniques, and massage, and yoga, and acupuncture…

And people find different approaches to help manage these symptoms and side effects. And so, it’s very unusual where we run into a situation where the side effects are unbearable and unmanageable. Usually, we can manage them in some form of way that allow people to have, again, a good quality of life and a meaningful life, even on prostate cancer treatment.

Katherine:                  

Thank you, that’s really helpful. I’d like to talk about the term “shared decision making.” What does that mean to you, exactly?       

Dr. Choudhury:   

So, shared decision-making really means that when the physician conveys information to a patient, that the patient really understands what’s being said, and what, really, the alternatives are – and the real risks and the benefits of the different alternatives. And so, if a patient goes to see a surgeon and they say, “Well, we should take this out,” and there’s never really discussion of what the risks and benefits of the alternatives are –and the alternatives could be just watching, or radiation, or even more intensive treatment, then that’s not really shared decision making.

But what I think is not exactly shared decision making is when the patient is getting information from really non-knowledgeable or non-reputable sources and then starts to come up with conclusions based on hearsay or people trying to sell them a product that really hasn’t been FDA approved or really tested. And so, those are situations where when the information is really not good, then we can run into troubles with communications. But there are a lot of really excellent sources for patient information that’s available, and the Prostate Cancer Foundation is a really good source, and a lot of the academic prostate cancer centers are really great sources of information.

And so, being educated and asking good questions is really the best way for a patient to feel comfortable that they’re not missing anything and that they’re, again, having all the information that they need to make a good choice for themselves.

Katherine:                   

Do you have any advice to help patients speak up if they’re feeling like they’re not being heard?

Dr. Choudhury:           

Sure. So, I mean, there’s never any barrier to bringing up concerns with whoever that you’re seeing, and if you feel like whoever you’re talking to isn’t being receptive to those concerns, then certainly, second opinions are very useful. But if you see multiple doctors and they’re kind of telling you the same thing based on good evidence, then you probably have to take in what they’re saying, and process it, and see if it really does apply to your particular situation.

But any cancer doctor who really has your self-interest in mind will be very open to discussing the concerns that you have, so you should absolutely bring them up.

Katherine:                  

To close, Dr. Choudhury: What would you like to leave the audience with? Are you hopeful?

Dr. Choudhury:          

Yes. I’m actually incredibly hopeful. There’s been such a transformation in our diagnosis and management of prostate cancer compared to when I first started as an independent attending back in 2012. In the last ten years, there’s been so many new treatments that’ve been approved in the last decade and a lot of newer technologies available for staging patients – really finding where their prostate cancer is.

And newer technologies for treating the cancer wherever it is and in a really smart way. And so, we can really individualize our treatments for the patient that’s in front of us being a bit more intensive for people with higher-volume or higher-risk cancers, and actually potentially being able to back off treatment, and actually stopping some of the testosterone-lowering drugs in patients who are responding exceptionally well to the medications and the local treatments that we’re giving them.

And then, also, I’m really hopeful about the newer treatments and newer technologies that are on the horizon. We have newer – what we call “molecularly targeted agents.” We have new approaches involving immune therapies that are being tested – newer radiation approaches. And I feel like all of this put together allows us to, again, satisfy the goal of maintaining patients’ good, healthy, meaningful quality of life moving forward.

Katherine:                  

Yeah. Dr. Choudhury, thank you so much for taking the time to join us today.

Dr. Choudhury:           

Oh, you’re welcome. It’s so wonderful to have this opportunity.

Katherine:                  

And thank you to all of our partners. Please continue to send in your questions to Question@PowerfulPatients.org, and we’ll work to get them answered on future programs. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for being with us today.