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Advanced Prostate Cancer: What You Need to Know About Evolving Treatment and Research

Advanced Prostate Cancer: What You Need to Know About Evolving Treatment and Research from Patient Empowerment Network on Vimeo.

Research is evolving quickly, leading to an increase in treatment options for advanced prostate cancer patients. Expert and researcher Dr. Rana McKay reviews current prostate cancer treatment options, discusses where clinical trials fit into a care plan, and shares advice for partnering with your healthcare team.

Dr. Rana McKay is a Medical Oncologist at UC San Diego Health. Learn more about Dr. McKay.

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

What Prostate Cancer Research Is Showing Promise

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Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. When advanced prostate cancer patients discussed potential treatment approaches with their healthcare team, it’s important that they understand all of their options including where clinical trials fit in. So, the patient empowerment network created the Evolve Series, to help patients understand the latest research and how it may impact them. In today’s program, we’re joined by a prostate cancer expert who is going to explain and discuss research highlights, and provide tips for having productive conversations about your care. Before we meet our guests, though, 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 a guide to help you 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. 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. Rana McKay. Dr. McKay, welcome. Would you please introduce yourself?  

Dr. McKay:

Absolutely. My name is Rana McKay, I’m a genitourinary medical oncologist, at the University of California in San Diego. It’s a pleasure to be here, with you, on this program today.  

Katherine:

And the sun is shining.  

Dr. McKay:

Yes.  

Katherine:

Which, is always good. Well, thank you so much for taking the time to join us today. Before we get into the discussion, Dr. McKay, I’d like to have you tell us how the landscape of advanced prostate cancer has changed over your career.   

Dr. McKay:

Oh, my goodness. It has absolutely rapidly evolved over the last decade. I think when I was just starting my career, it was right around the time where Abiraterone and Enzalutamide were being heavily tested and just getting approved and entering into the clinic. And as we think about all of the evolution that’s happened since that time, we now have multiple androgen receptor pathway inhibitors in the clinic. We have radioligand therapies in the clinic, radium-223. The first radioligand therapy across any solid tumor malignancy to improve overall survival and on the heels of that, most recently, lutetium PSMA, which is a targeted radioligand therapy.  

There’s several different kinds of chemotherapies, and I think two more diagnostics have evolved. We are now integrating molecular profiling across multiple areas in the disease natural history and actually have several FDA-approved treatments based off of results of molecular profiling, whether that be germline hereditary testing or just tumor testing like, PARP inhibitors and immunotherapy. And then, additionally, to kind of continue on that same thought of our diagnostics changing is one of the greatest disruptors in our treatment of prostate cancer has been the introduction of PSMA PET imaging that has really revolutionized our ability to be able to detect disease at lower levels of PSA.  

And that’s opened up options for focal therapy, radiation therapy, and other sorts of strategies. So, it’s really been just remarkable, all of the different advances that have occurred in prostate cancer over the last decade.  

Katherine:

Well, let’s dive into developing research and what it could mean for patients. Are there recent research highlights that you could share with the audience?  

Dr. McKay:

Absolutely. I think the newest approvals that have occurred in prostate cancer have been the approvals of combination PARP inhibitors, which block the ability of cancer cells to repair their DNA combined with hormonal agents such as abiraterone (Zytiga) or enzalutamide (Xtandi) for patients who have specific mutations in their tumor and their tumor is no longer responding to treatment. Those are the newest FDA approvals that were recently highlighted and shared.  

Katherine:

What areas of research do you specialize in? 

Dr. McKay:

The areas of research that I specialize in are particularly around novel therapeutics for patients with advanced prostate cancer, biomarker development precision medicine strategies for patients across the spectrum. And actually, also, in the localized setting, thinking about how we can attempt to cure more patients with prostate cancer by integrating our systemic therapy with surgical and radiation strategies to improve survival outcomes for patients and ultimately, cure it for patients by using effective systemic therapy early on so patients never recur.   

Katherine:

Yeah. We’ve been hearing a lot recently about innovations in technology. How are these advances accelerating prostate cancer care?  

Dr. McKay:

Innovations of technology have absolutely been revolutionizing prostate cancer care I think from the diagnostic side, there’s new imaging modalities that are getting more refined. On the molecular side, there’s now different kinds of genetic tests. And our ability for us to do these tests, and do them quickly, and get results in real time that we can make decisions on we’ve come a long way from when we first sequenced the human genome. We’re now able to do that so quickly multiple times over in a very streamlined kind of way. And then, I have to say that there’s been tremendous improvement in our modalities of administrating therapies.  

So, our therapies are getting more novel, they’re getting more precise. What I mean, by that is targeted radioligand therapy, targeting linking a small molecule that binds PSMA, labeling it with a payload that is radiation therapy or kind of radio therapy/radio particle doing the same thing with chemotherapy, developing antibody drug conjugates. There’s androgen receptor degraders. There’s different ways of administrating immunotherapy by specific antibodies. So, there’s just the different sorts of treatments that are out there.  

We’ve just come such a long way from hormone therapy, which is still very important in chemotherapy to other different modes of action with the different systemic treatments we have.  

Katherine:

What about individual patients? Is there research into understanding a person’s – just one person’s disease?  

Dr. McKay:

Absolutely. I mean, that is in essence, precision medicine. I think we are now molecularly profiling tumors that is standard of care for anybody with advanced disease to undergo hereditary tumor profiling and – or hereditary profiling of just normal cells in the body, if there’s any sort of genetic abnormalities. But also, the tumor itself, and able to do that all for the actual biopsy specimen, or surgical specimen, and also blood. And then, based off of that individual’s genetic makeup, or the genetic makeup of the tumor, or the immune profile of the tumor actually trying to target therapy.  

There is a clinical trial that we are eagerly developing through the alliance, which we hope will open to enrollment before the end of the year, called the PREDICT Study. And this study is using that very notion of taking somebody’s DNA and RNA from their specific tumor, and based off of their results, strategizing the treatment around what kind of genetic makeup is in the tumor. And I think we’re moving towards that.  

Katherine:

What about common genetic mutations and what are you learning about people who have other genetic mutations like the BRCA mutation?  

Dr. McKay:

For patients who have BRCA mutations, first I’ll say, the prevalence of BRCA mutations varies across the stage of prostate cancer that somebody has. In the localized setting, the prevalence is a lot lower on the order of 2 to 4 percent depending on somebody’s risk profile. In the advanced setting, it is higher, 6 to 8 percent. Patients who have BRCA alterations are particularly susceptible to PARP inhibitors, which are oral drugs that can be given that when given in an individual who’s got a BRCA mutation, can cause cell death; can cause a tumor cell to die. And so, that’s a very good thing.  

 I think the other thing, if thinking about the type of BRCA alterations, if there’s something that’s hereditary, this information is prognostic and predictive in that in can guide how people are going to – how we think they may do and what they may respond to. But it’s also really important because it can inform cascade testing for family members. It could also inform screening for secondary cancers in that individual who has prostate cancer with a known BRCA alteration. So, I think there’s a lot of personalization that happens based off of the molecular profiling results.  

Katherine:

It’s all so exciting, Dr. McKay. But progress can only be made with patient participation in clinical trials, as we know. So, when should a patient consider participating in a trial? 

Dr. McKay:

Thank you so much for bringing this point up. I think our clinical research is critically important to advancing the field. Clinical trials, I think, are really – they offer our patients the treatments of tomorrow today, quite honestly. And I think the way trials are designed, they’re designed to test different treatment modalities, test in reference to the standard of care. I think at any point in time, anybody can think about enrolling on a clinical trial. I think sometimes there’s this false notion that, “I’m not going to enroll in a trial until later on, until I’ve failed all different kinds of treatments.” That’s not true.  

 I think at any juncture along the way where a decision is being made around initiating a systemic therapy, or proceeding with a surgical intervention, or radiation intervention it’s always worthwhile to stop and ask, “Are there any clinical trials that I could be eligible for right now? And if so, what are they? So, I think it’s really important, I think, for patients to know that and to ask of their clinicians that are caring for them, “Are there any clinical trials?”  

And it may be that patients, not to say, may need to travel, but if they’re not necessarily at that institution where somebody may be receiving their care with a clinician asking their doctor, “Are there other trials at places close by where I can go and explore?” I think that’s a really important thing.  

Katherine:

Yeah. That’s good information. What about common misconceptions? What are you hearing from patients about their fears and hesitations about participating in the trial.  

Dr. McKay:

Yeah. I think a lot of patients have a fear of, “I don’t want to be a hamster or a guinea pig. I don’t want to get placebo. I don’t want to get suboptimal care.” So, I think, to step back, I think the clinical trials are designed where actually patients are followed very, very closely, probably even more closely than I think would be in general with laboratory tests, PSA testing, imaging, at critical time points to assess that any therapies or strategies is working. Many trials are not necessarily placebo-controlled trials.  

Placebo-controlled trials are really only utilized in the context when somebody may – where the standard of care is to either do nothing or do one drug alone, not two drugs, and then, somebody’s getting one drug and getting a placebo. So, the placebo-controlled trials are really, first off, they’re later-staged studies, they’re usually Phase III studies, or large Phase II studies that have gotten pretty far on the runway of clinical trial and clinical drug development.  

 And it’s in the context of, you know, “Well, if I didn’t do the clinical trials, I’m probably not going to do anything,” or I’m not going to – you know, “If I decided to not do the trial, I would get no treatment, but if I’m doing the trial, there’s a 50 percent chance I’ll get no treatment and 50 percent chance I may get something. So, we have to think about, “Well, what is the standard of care?” and the standard of care matters because that is what it’s being compared to. If the clinical situation is that the standard of care is to monitor, then that’s where a placebo may be utilized.  

But if a standard of care is that somebody should get treatment with X drug, then that X drug would be in the controlled arm of the study.  

Katherine:

Yeah.  

Dr. McKay:

But not every trial has a placebo.  

Katherine:

What would you say to someone who is nervous or hesitant about participating in a trial?  

Dr. McKay:

Yeah. Very good question, I think. Talk to your clinician. Talk to your doctors about those fears. What are the reservations? What are the concerns? Sometimes, I think the unknown is always – the fear of the unknown kind of causes a lot of angst. But when people are on a clinical trial, when you’re on a clinical trial, you are in control. Some people don’t believe that, but you are, at any point in time, you can decide to stop. You don’t even need to have a reason for why you decide to stop. At any point in time, if something is not working for you, you have choice.   

And so, I think that is something that is really important for patients to know that you’re actually in control, you’re being watched very closely, being watched very carefully for safety toxicity. If there’s a toxicity, people are not going to – you’re not going to just stay getting the same regiment in the exact same way if you’re not tolerating it. If something isn’t working, you’re not going to continue receiving the therapy that’s no longer working just because you’re on a clinical trial. 

Katherine:

Right.  

Dr. McKay:

And you’re in control; at any point in time, you could say, “I don’t want to participate anymore.”  

Katherine:

Yeah. Are there barriers for accessing trials? And if so, do you have any recommendations for how to tackle those?  

Dr. McKay:

Yeah. I think there are barriers to accessing trials. I think it can be very overwhelming because there’s thousands of clinical trials that are being conducted for people with prostate cancer. And I think as a patient, sometimes it’s hard to navigate that. But I think the thing to take home is that you do not have to do it alone, and you should not do it alone because I think half of the trials that are out there, the large bulk of them may not necessarily be directly applicable to you or relevant for you.  

 And so, I think talking to your clinician about that, I think seeking care, even if just for a second opinion at an NCI-designated cancer center, or NCI-designated comprehensive cancer center is probably a good idea. You know, if you’re hearing the same message from your local clinician then that’s great. If there’s more options that are being presented to you, that’s great, those are more options that you could tap into. I think talking to patients who have gone on a trial may also help away some of the fear around participating in a clinical trial, and there’s lots of platforms where that could take place either asking your physician, or the American Cancer Society, or other societies can help connect patients to one another.  

Katherine:

Okay. I’m glad you mentioned some of the resources because that’s what I was going to ask you about. Well, I want to mention to our audience that if you want more basic information about prostate cancer, PEN has created a prostate cancer toolkit, which includes information about diagnosis and staging. And you can find it at powerfulpatients.org.  So, before we move onto understanding current treatment options, Dr. McKay, what are the goals of advanced prostate cancer treatment? And how do they vary by patient?  

Dr. McKay:

Yeah. I do think the goals can vary. I think in my mind, a lot of times, it’s making people live longer, making them feel better. Those are the two salient goals and if our therapies are not achieving one or other of those two goals then we need to rethink the strategy. But different people are different, and they may weigh the risks and benefits of any given therapy, or the slated benefit with the slated risk through a different lens. And I think it’s critically important to ensure that you’re having those communications with your doctor about the things that matter to you and the things that are really important to you. 

Especially, for people who have advanced prostate cancer. So, I think that can help your clinician strategize, “Okay, is this an individual who wants the kitchen sink everything that I can do even if that means more toxicity that I’m going to offer this thing? Or is this a situation where, you know what, unless there’s data that the kitchen sink is going to work, I really kind of want to temper things and try an approach that’s going to be effective, but maybe not associated with that degree of toxicity.” So, those kinds of conversations absolutely need to be happening.   

Katherine:

Yeah. With all the recent advances in treatment, is there a standard approach now to treating someone with advanced disease? And if so, what is it?  

Dr. McKay:

Yeah. There absolutely is a standard approach. There’s guidelines that are based off of the FDA-approved regimens of the different agents that can be utilized. There’s data regarding sequencing though, I think there’s more data that needs to be had on sequencing. There are guidelines on when to do germline testing, when to do tumor profiling, when to integrate PSMA PET imaging, the standard hormonal agents, who to use them. So, I do think that there are – there’s a set framework of appropriate management and treatment. But there’s a lot of personalization that is overlaid on top of that rubric. And I think that’s the art of medicine.  

Katherine:

Right. Is there testing to understand if a patient’s disease is more aggressive? Or maybe will respond to a certain type of therapy before you begin it?  

Dr. McKay:

Yeah. A very good question. And I think predictive biomarkers, as you described them, there are several for men with prostate cancer, but there’s not a ton of them. So, we know that homologous recombination repair alterations, HRR, gene alterations, particularly BRCA 1, 2, probably 2, we know that those are biomarkers of response to PARP inhibitors. We know that patients who have high tumor mutation burden, or have a mismatch repair, that those are markers of response to immunotherapy. We know that if people have a certain level of PSMA PET vividity on their PET scan, that that’s a biomarker for receiving lutetium PSMA.  

Those are the main biomarkers that are actually in use in the clinic to date. But I think there’s a lot more that I think are being explored from mutations in the androgen receptor, or amplifications in the androgen receptor, being potentially predictors of response to different degraders, different kind of hormonal agents. There’s certain tumor suppressor gene mutations that may predict that patients may do a little bit better with chemotherapy. So, there’s other markers that are being looked at, but they don’t have the same robustness as the BRCA 1, 2 and other ones that I talked about. 

Katherine:

Yeah. How does a patient’s health and lifestyle impact what treatment approach is right for them?  

Dr. McKay:

I mean, health and lifestyle, diet, and exercise, nutrition, sleep are so important. I think that one of the backbones of treatment for hormonal therapy is androgen deprivation therapy. There can be negative consequences with regards to muscle mass, bone mass, other things related to that therapy. So, I think it’s critically important for patients to maintain a healthy diet, making sure they’re getting appropriate exercise, weight-bearing, resistance training.  

And I think, too, this helps people with their functionality, with their ability, their reserve, and ability to tolerate treatment or tolerate more aggressive treatment. So, half of my clinic is talking about diet and exercise, and how to optimize individual health when people are on therapy. 

Katherine:

Yeah. Mentally, a good diet and sleep –  

Dr. McKay:

Yes.  

Katherine:

And exercise is going to be helpful.  

Dr. McKay:

Yes.  

Katherine:

As well. What about comorbidities? Do they play a role?  

Dr. McKay:

They absolutely do play a role. I think comorbidities like cardiovascular disease, diabetes absolutely can play a role. The hormone therapies, patients can have a propensity to gain weight, they can have a propensity to have worsened cholesterol being on hormone therapy, which can then affect somebody’s cardiovascular health. And so, some of the drugs cause increased hypertension. So, I think understanding the different comorbidities that any individual may have is important in selecting the best therapy, “Well, actually, if you’ve got X, Y, Z going on, maybe I’m going to shy away from this, but lean more towards that.”  

I think making sure that your physician knows about that and knows about changes that happen along the way. Sometimes, people with prostate cancer, many a times they have a long, natural history where they’re seeing the physician caring for them for their prostate cancer over many, many years. And somebody’s medical history, when they first saw that individual, it’s going to change and evolve over time as different things happen. And so, I think keeping your clinician that’s caring for you for your prostate cancer informed of all the other non-cancer things that are happening I think is a really good idea.  

 If you had a fracture, that’s actually a really important thing for somebody who’s got prostate cancer. Or “Gosh, my primary care just started me on Metformin because they think my blood sugar is a little bit off.” These are important things, I think, for clinicians to know about.  

Katherine:

Yeah. It’s all about communication, isn’t it?  

Dr. McKay:

Absolutely. Yeah.  

Katherine:

Don’t worry about over-sharing.  

Dr. McKay:

Yeah.  

Katherine:

Yeah. Speaking of sharing, shared decision-making has become the gold standard, really, for encouraging a successful relationship between a patient and their healthcare team. What does shared decision mean to you as a provider?  

Dr. McKay:

Yeah. I think shared decision is an open dialogue. I think it’s an open dialogue with the physician, with the patient, sometimes, often times, the patient’s caregivers, and families, and loved ones may be involved in that process, where we’re talking about, first off, establishing the goals. Well, what are the goals? And I think, when we start with the goals then, we can say, “Okay. Well, what are the things that we can do to achieve those goals?” And I think sometimes we just dive right into, “Well, what are we going to do with the next step?”  

So, I think establishing what the goals of therapy are the things that matter to any individual patient and their family is important. And then, from there, working on, “Okay. Well, aligning with those goals, these are the different things that you can do. These are the pros and cons of the different things that you could do,” and making an informed decision about the next step.  

Katherine:

What questions should a patient ask about potential treatment options?  

Dr. McKay:

One, what are the different treatment options? You know, sometimes I think that statement doesn’t get said enough. What are the standard of care options? What are the clinical trial options? Ask are there radiation therapies, surgical options? That may be a relevant question for some individuals, some individuals, not. Being very open like, “Okay, I’m hesitant about chemo. Let me explore that.” Well, where does that hesitancy stem from? What’s the fear about chemo? Are there chemotherapy-sparing options right now? Or how can we kind of dispel the fear or myth around chemotherapy?  

So, I think these are the questions that I think a patient can ask. How is a therapy administered? Where do I go? How would I receive different therapies are given at different modes of administration? I think those are good questions. Who do I call if something happens to me on the weekend or on a holiday? Who do I reach out to? What are the phone numbers? Give me all the phone numbers. Get them in my phone. Save them in there, so you know, who to reach out to if you ever need something, if you ever need assistance.  

Katherine:

Yeah, that’s really good advice. Why should a patient consider finding a prostate cancer specialist?  

Dr. McKay:

I think a patient should consider finding a prostate cancer specialist because quite honestly, the field of oncology is getting to be so expansive, and there’s so many changes in guidelines on a monthly basis, sometimes across all the different malignancies. So, I think having a specialist who understands the nuances of the different iterations of treatment for people with prostate cancer, and how to personalize that for a given patient is really important. And I think it can be associated with improved outcome.  

I will say that the note about clinical trials, there have been several studies that had been conducted that have actually noted that patients who enroll on a clinical trial, whether or not that clinical trial is positive or not, independent of the results of the trial. But just enrolling on a clinical trial is associated with improved outcome. And I think a lot of it stems with where people get their care, eligibility for trials, the scrutiny that happens when people are on trials, and sort of, level of expertise where people get their care and so forth.  

Katherine:

Yeah. Thank you for sharing all of this information, Dr. McKay, it’s really vital. As we close, what final thoughts would you like to leave our audience with? Why are you hopeful?  

Dr. McKay:

I am very hopeful because of all of the amazing technologies that are in the pipe right now, currently in development, some early on, some close to the finish line that I think are certainly going to change the way that we view and treat prostate cancer. I think it’s exciting to see where the field has come and where the field is going, and know that you are not in this alone, and there’s a lot of progress that is being made, and a lot of hope that is out there for individuals who have prostate cancer.  

Katherine:

Well, Dr. McKay, thank you so much for taking the time to join us today. We really appreciate it.  

Dr. McKay:

Wonderful. It’s my pleasure.  

Katherine:

And thank you to all of our collaborators.  

If you’d 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 the 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.  

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.

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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.

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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

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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.

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

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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.

Should Prostate Cancer Patients Consider a Treatment in Clinical Trials?

Should Prostate Cancer Patients Consider a Treatment in Clinical Trials? from Patient Empowerment Network on Vimeo.

Prostate cancer expert Dr. Andrew Armstrong explains how prostate cancer clinical trials work and discusses why patients should feel confident exploring this option at any stage of their cancer journey.

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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Key Questions for Prostate Cancer Patients to Ask Before Joining a Clinical Trial


Transcript:

Katherine Banwell:

At what point should a prostate cancer patient consider participating in a clinical trial? 

Dr. Armstrong:

Sure. If you look at the National Comprehensive Cancer Network, NCCN guidelines, you’ll see that clinical trials should be discussed along all parts of the journey. 

And that’s because clinical trials often can change how we think about cancer, how we treat cancer, can improve cure rates, can improve survival. Most of our drugs and treatments that have been successful in all cancer have been the result of clinical trials. 

And it’s not always appropriate, though. We have very many treatments that can cure patients, and we don’t want to interfere with that, but sometimes a clinical trial can layer on top of that cure rate. 

But many patients, their cancer becomes resistant to proven therapies. That’s certainly an area where clinical trials can make a big difference, either to put off chemotherapy or more toxic therapies, or in patients who have exhausted proven therapies. That’s certainly appropriate. 

But sometimes clinical trials do not involve placebos. They involve combination therapies, they involve layering on top several approaches to try to improve the survival on top of standard of care.  

And so as a director of a research program, we have all sorts of trials. They come in Phase I, Phase II, Phase III. Really only the Phase IIIs involve placebo controlled or controlled trials. Phase II tend to be early studies, where everybody gets a therapy and it’s preliminary to determine efficacy. Phase I is really trying to determine the safety and dosing of an experimental drug. But patients can benefit across the spectrum. 

So, it’s important, particularly if you have advanced disease, to go to a site, like a comprehensive cancer center, for a second opinion to see if there is alternatives to what you might get in the community.  

Katherine Banwell:

Yes. What would you say to someone who might be hesitant to participate in a trial? 

Dr. Armstrong:

Participation in a trial involves shared decision-making, just like being diagnosed, embarking on initial treatment, even embarking on standard of care treatment. Everything is shared decision-making in terms of risks and benefits.  

Sometimes a trial is not in a patient’s best interest, and it’s important for a physician to be upright about that and up front about the risks of a trial. 

I think when patients have exhausted proven therapies, it’s quite appropriate to talk about therapies that might be in the research pipeline that are showing some promise, that have demonstrated at least success in the laboratory or in small numbers of patients coming before.  

For example, in 2022, a brand-new drug just got approved called Pluvicto, or PSMA lutetium. This is a new smart bomb for prostate cancer. Just last year it was a research drug, but this year it’s successful and being used in the clinic. All those hormone drugs I mentioned earlier, those were research drugs five years ago. So, we don’t make advanced, we don’t extend lives without participating in research. We’re not happy with the way things are, we want them to be better. 

And the only way to make them better is by studying them. And not all of these trials are successful, unfortunately, but many are, and that’s why we are seeing men live longer and have better survivorship nowadays. 

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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How Can Prostate Cancer Patients Access Clinical Trials?


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.

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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.  

What Are the Treatment Options for Early Stage Breast Cancer?

What Are the Treatment Options for Early Stage Breast Cancer? from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Adrienne Waks reviews available treatment approaches for patients with early stage breast cancer and explains the role of sub types when choosing a treatment plan.

Dr. Adrienne Waks is the Associate Director of Clinical Research at Dana-Farber Cancer Institute. To learn more about Dr. Waks click, here.

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Transcript:

Katherine:

Well, let’s get into the specific treatment options that are available for breast cancer patients. Could you tell us about those?  

Dr. Waks:

So, fortunately, the answer to that question is enormous, because we have so many effective treatment options in breast cancer and generally our patients do very well in the long term when they are diagnosed with early stage breast cancer, so stage I or II or III breast cancer.  

That might involve the breast, it might involve the lymph nodes under the arm, but it hasn’t traveled anywhere else in the body. So I’ll set aside metastatic breast cancer and just talk about stage I, II, and III. 

So, as you may know, we think about as medical oncologists we completely separate treatment considerations for three different subtypes of breast cancer. Those are hormone receptor-positive, HER2-positive and then triple-negative. So, again, highlighting just important developments and not really the overall treatment planning for each of those subtypes, in ER-positive disease or estrogen receptor-positive disease hormonally-driven, estrogen-driven breast cancer – those are all sort of terms for the same thing, I think there have been a couple of important developments over the last few years.  

Probably the most important recent one is the new understanding and demonstration that the CDK4/6 inhibitor abemaciclib, the brand name of that drug is Verzenio. 

That drug when we administer it for two years after a patient has had their surgery and in conjunction with alongside the antiestrogen medicines; the antiestrogen medicines are usually done for a minimum of five years, when we add on to that the CDK4/6 inhibitor abemaciclib, we see that for women with higher risk disease, so maybe some lymph node involvement or a large tumor in the breast or both that the addition of the Verzenio, the abemaciclib seems to decrease their risk of recurrence of breast cancer a couple of years out. So, that’s been an important exciting development. 

Again, not for all women within early stage estrogen-driven breast cancer, but for a little bit more advanced early stage disease like lymph node involvement. You know, we’re obviously always looking for ways to reduce that risk of recurrence for women who have a little bit more risk at diagnosis and the addition of abemaciclib was an exciting and welcome addition to our toolkit there. 

In HER2-positive disease, which is about 20 percent of breast cancers overall, I think what the recent years have brought us is increasing understanding that in many cases we give women too much chemotherapy and that we need to be – so, here it’s less about adding on. Like the Verzenio example I was just talking about and more about individualizing and figuring out in whom and how we can pull back from sort of the kitchen sink approach that we take often to treating a HER2-positive early stage breast cancer and be more thoughtful and more personalized in the amount of treatment that we give women with HER2-positive breast cancer. 

The reason for that is that we’re basically 20 years into understanding that for HER2-positive breast cancers we can treat those cancers very effectively with anti-HER2 antibody drugs like trastuzumab or Herceptin. We didn’t even know that until 20 years ago. And so, Herceptin, trastuzumab and similar drugs have really revolutionized how effectively we can treat women with HER2-positive breast cancers. And so, at this point, it’s becoming more and more clear that we can really lean more on our arsenal of anti-HER2 targeted therapies like Trastuzumab. Pertuzumab (Perjeta) is another one and trastuzumab MTNC and TDM1 is another one. 

So, we have all these excellent smart targeted treatments for women with HER2-positive disease, but yet the standard of care is still to give all those good rational targeted treatments with a whole bunch of chemotherapy that comes with a lot of side effects. 

I think more and more we’re figuring out that we can lean more on our anti-HER2 treatments and require less of the really side effect heavy chemotherapy, but how do we do that thoughtfully? We obviously don’t want to undertreat anybody, so how do we do that thoughtfully? How do we pick out the women who only need the anti-HER2 treatment and can get away with less chemotherapy. I think that’s really what’s exciting in HER2-positive early stage breast cancer right is how do we individualize and take advantage of targeted agents that we have? 

And then finally, in the third subtype of breast cancer which is triple-negative breast cancer which accounts for about 10 percent of breast cancers, the most exciting development there clearly in the last year or so is the realization and the demonstration in randomized clinical trial that we can improve outcomes for those women if we give them not just chemotherapy but also chemotherapy combined with immunotherapy and specifically the immunotherapy agent called pembrolizumab or Keytruda. 

So, up until a year or two ago, the standard for a stage I or II or III triple-negative breast cancer was to get a multiagent chemo regimen and chemo was really the only type of option we had to treat those triple-negative breast cancer patients and now we know from a major important clinical trial called Keynote 522, that if we take a standard chemo backbone and add Pembrolizumab immunotherapy onto it, that we can help those women do better in the long term. So, that’s really a pretty new in the last one or two years standard of care for triple-negative breast cancer. 

And I guess the last thing I’ll say is not about one of those three subtypes of breast cancer but specifically for women with a BRCA1 or BRCA2 mutation associated with their breast cancer, which is a minority. It’s about 5 percent of breast cancer patients. Obviously, the proportion changes depending on your subtype of breast cancer and your age when you’re diagnosed, but for women who have a breast cancer associated with BRCA1 or 2 mutation and have a higher risk or early stage breast cancer. 

So, again, they have a number of lymph nodes involved or a big tumor in the breast or something like that, we now know that we can add on one year of the PARP inhibitor medication called olaparib or Lynparza to the postoperative treatment of those breast cancer patients in addition to whatever other treatment they got; the antiestrogen pills, the chemotherapy, or a combination of those two, and with the addition of olaparib or Lynparza for a year that we can again see better long-term outcomes for those patients and help them avoid recurrences. 

So, that’s not a majority of breast cancer patients but is a targeted treatment that we’re very excited about that definitely makes an important contribution to reducing risk for women with a BRCA1- or BRCA2-associated cancer or men for that matter. I’m saying women, but it could absolutely apply to men. 

How Is Metastatic Breast Cancer Treated?

How Is Metastatic Breast Cancer Treated? from Patient Empowerment Network on Vimeo

Breast cancer expert Dr. Adrienne Waks discusses treatment approaches for metastatic breast cancer and explains how research is evolving.

Dr. Adrienne Waks is the Associate Director of Clinical Research at Dana-Farber Cancer Institute. To learn more about Dr. Waks click, here.

See More from Thrive Breast Cancer

Related Resources:

What Role Do Breast Cancer Patients Play in Care and Treatment Decisions?

Key Questions Patients Should Ask Before Participating in a Breast Cancer Clinical Trial

What Are the Treatment Options for Early Stage Breast Cancer?


Transcript:

Katherine:

What about people who have metastatic disease? What treatment advances are available for them?  

Dr. Waks:

Yeah. You know, I think that’s an incredibly important question and a totally different set of discussions than we have with women with early stage breast cancer and unfortunately and unacceptably at this point for a woman diagnosed with metastatic breast cancer still typically that can become a life-threatening diagnosis. 

So, it’s exceptionally important that we rapidly improve the treatment options that we have for women with metastatic breast cancer. Maybe everybody says this every year, but I think that this year, 2022, has been a particularly exciting year in terms of advances that we’re making in the treatment of metastatic breast cancer, really of all subtypes. I would say the most exciting class of drugs or type of drugs that’s coming out in breast cancer and in all malignancies honestly, is called antibody drug conjugates, which is to say an antibody. So, a molecule that’s targeted to some particular approaching on a cancer cell surface and then is attached to or conjugated to a chemotherapy molecule.  

So, the antibody is like a smart delivery system directly to the cancer cell for what’s call a payload, basically like a sort of action molecule or the killer molecule, which is the chemotherapy. 

Those kinds of antibody drug conjugants have made a huge impact in recent years in improving outcomes for women really with all subtypes of breast cancer, so that drug class I think is a very exciting one to watch in general. In terms of specific recent developments in metastatic breast cancer, so probably the biggest blockbuster development over the past year and really over just the past three months is the understanding that we can break out a subtype of metastatic breast cancer that we really didn’t even talk about before which is called HER2-low breast cancer. So, before if you asked me in May of 2022, there really were only two types of HER2 readouts for a breast cancer tumor. 

There was a HER2-negative breast cancer tumor and there was a HER2-positive breast cancer tumor and as I already told you, the HER2-positive accounts for about 20 percent of breast cancers overall. The other 80 percent are HER2-negative. And so, historically, again you asked me three months ago I would have said if you’re HER2-positive and that 20 percent will give you these different HER2-directed treatments and if you’re not, we can’t use those. And what’s changed is that we’ve developed new antibody drug conjugants. So, drugs that are targeted against in this case the protein HER2 that seem to be so effective and work so well, that you don’t truly have to be HER2-positive.  

You can be HER2-low and still benefit from these treatments, which is to say your cancer has a little bit of HER2 protein on the surface of the breast cancer cells but not a lot. So, not enough to make it positive but enough to make it low in its designation. 

That’s actually a large proportion of breast cancer patients. It’s over 50 percent of breast cancer patients, so it’s significantly more than HER2-positive, so a large proportion of breast cancer patients actually fit into this new category called HER2-low and we now know from data that were presented in June of 2022 and then published in the New England Journal of Medicine, which is our biggest most high profile academic medical journal, we know that for patients who fall into that HER2-low category, again that’s more than 50 percent of breast cancer patients, that they can, if they have a metastatic breast cancer, benefit from this new antibody drug conjugate called trastuzumab deruxtecan (Enhertu).  

When it was compared to the existing chemo options we have for those patients which do have some efficacy but nonetheless, when trastuzumab deruxtecan was compared to the existing chemo options, it clearly looked better for patients with HER2-low breast cancer. So, that was not just an exciting advance in terms of new treatment options which we always love to be able to offer to patients but also in terms of breaking out this entirely new designation and subcategory that captures more than half of our metastatic breast cancer patients and helping us to offer them something new and hopefully will be a pathway for other drugs to be developed in this space and for this new subcategory. 

So, that was very exciting. I’ve been talking about it with patients all the time in the past just three months since those data came out.  

You know, a second antibody drug conjugate that has also been very exciting in recent months and recent years is called sacituzumab govitecan which Trodelvy is the brand name of that one. That’s an antibody drug conjugate that’s targeted against a different protein on the cell surface that’s targeted against the protein Trop-2, so that’s where the Trodelvy comes from. It’s targeting Trop-2. That’s an antibody drug conjugate that we’ve known for probably three or more years now can be very effective in triple-negative metastatic breast cancer. So, we’ve had that option for a number of years in metastatic triple-negative breast cancer. 

But again, just in the past few months have gotten good and exciting data that this Trodelvy or sacituzumab drug also works in estrogen-driven breast cancers.  

And so, it’s giving another option to patients with not just triple-negative but also estrogen-driven breast cancer. So, that was another very recent development just in the last three months or so. 

Katherine:

That’s really exciting.