Tag Archive for: molecular testing

Understanding Currently Available Non-Small Cell Lung Cancer Treatments

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Understanding Currently Available Non-Small Cell Lung Cancer Treatments from Patient Empowerment Network on Vimeo.

What options are available to treat non-small cell lung cancer? Dr. Erin Schenk, a lung cancer specialist and researcher, defines personalized medicine for the audience and discusses lung cancer treatment options, including clinical trials.

Dr. Erin Schenk is a medical oncologist, lung cancer researcher, and assistant professor in the division of medical oncology at the University of Colorado Anschutz Medical Center. Learn more about Dr. Schenk.

See More From INSIST! Lung Cancer

Related Resources:

An Expert Explains Predictive Biomarker Testing for Lung Cancer

An Expert Explains Predictive Biomarker Testing for Lung Cancer

 Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing

 Personalized Lung Cancer Treatment | Key Factors to Consider

Personalized Lung Cancer Treatment | Key Factors to Consider

Transcript:

Katherine Banwell:

We’re hearing the term personalized medicine a lot these days. Would you define the term for our audience? 

Dr. Erin Schenk:

Absolutely, and I think the treatment of non-small cell lung cancer is one of the poster childs for children – for personalized medicine because based on the result of the biomarker testing that’s what drives my choice of therapy because the biomarkers help to tell me what is this cancer most likely to be vulnerable to and that in my mind that’s a wonderful application of the promise of personalized medicine.   

Katherine Banwell:

Okay. Let’s move on to treatment now, Dr. Schenk. Would you walk us through the current treatments being used to treat non-small cell lung cancer?  

Dr. Erin Schenk:

Absolutely, and there are a broad range of options, and thankfully we have so many choices in how to best help patients. And it’s often why visiting with a center that sees a lot of patients with lung cancer can be beneficial so that you have all of the parties at the table that need to be there as we’re making these treatment decisions. So, I would start thinking about patients with early-stage disease. Often surgery if tumors are small enough and there’s not you know, no lymph nodes are involved with the cancer and it’s not anywhere else.  

Sometimes surgery is all that patients might need in terms of their treatment. Those are for patients with smaller tumors and really early-stage disease. As we move forward in the stages, meaning going from stage one to stage two, so a little bit bigger of a tumor, lymph nodes might be involved.   

That’s when really the multi-disciplinary approach happens, and what I mean by that is for example, at my institution where people like me, medical oncologists, radiation oncologists, and surgeons all sit down together to talk about a patient, their scans, you know, what is their health status, what is their biomarker testing, to try to come together to form a treatment approach. And so, at our institution, you know, frequently in stage two to stage three tumors based on biomarker testing we either select upfront surgery followed by chemotherapy followed by sometimes targeted therapies or TKIs.   

Those are the medicines, the TKI, those are the medicines that are really dependent on the presence of biomarker testing. So, the biomarkers often tell us for example if there’s an EGFR mutation. If that’s present then I would use an EGFR TKI, for example. 

But if those biomarkers don’t show an alteration where I have TKI to use, then we frequently are giving patients chemotherapy plus immunotherapy before surgery. This approach is called a neoadjuvant chemoimmunotherapy approach, and it’s one of the newer changes to lung cancer care within the past year that I think really is going to have a positive impact on outcomes for patients with lung cancer.  

So, just again in broad strokes, and then as we move into stage three patients where we can’t resect the tumor, that’s where we give chemotherapy medicines plus radiation therapy. Oftentimes followed by immunotherapy and then when patients have disease that spread outside of the chest, outside of the lungs, the metastatic setting or stage IV, that’s when we think about the whole host of therapies available through medical oncology, systemic therapies is another way to call them.  

And there we think about immunotherapy-based treatments plus or minus chemotherapy or we think about targeted therapy-based approaches with those TKIs. And again, it’s all based on those molecular markers, those biomarkers. 

Katherine Banwell:

Do clinical trials play a role in lung cancer treatment? 

Dr. Erin Schenk:

Clinical trials are incredibly important for the treatment of lung cancer. These are the tests and the procedures that we do that have continuously advanced our ability to care for patients with lung cancer. You know, it was clinical trial data that helped us get alerted to doing chemotherapy and immunotherapy before surgery really can help patients do better. And similarly, clinical trials have helped us define when do we use TKIs or targeted therapies. 

So, I think that’s another great question to ask your team of, “Based on all of the information you know about me and my cancer are there clinical trials options that are available here where I’m at or ones that are really interesting or appealing elsewhere that might be worthwhile for me to consider?” So, clinical trials are a critical part of how we help patients do better.  

Non-Small Cell Lung Cancer Essential Testing | What You Should Know

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Non-Small Cell Lung Cancer Essential Testing | What You Should Know from Patient Empowerment Network on Vimeo.

What tests are needed for a lung cancer diagnosis, and how might the results affect treatment options? Dr. Erin Schenk reviews the most common tests for lung cancer, including biomarker testing, and how the results may be used to determine the most appropriate therapy for your particular disease.

Dr. Erin Schenk is a medical oncologist, lung cancer researcher, and assistant professor in the division of medical oncology at the University of Colorado Anschutz Medical Center.

See More From INSIST! Lung Cancer

Related Resources:

Understanding Currently Available Non-Small Cell Lung Cancer Treatments

 Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing

 Personalized Lung Cancer Treatment | Key Factors to Consider

Personalized Lung Cancer Treatment | Key Factors to Consider

Transcript:

Katherine Banwell:

What are the various subtypes of lung cancer, and how are they identified?  

Dr. Erin Schenk:

Absolutely. So, there are a number of different subtypes of lung cancer that are important for us to identify, because it helps to stratify or helps to select the right treatment approaches for a patient. So, usually when someone is diagnosed with lung cancer there was a scan done at some point that noticed a mass or masses in the body. 

What happens next is a biopsy happens where a needle is used to sample the tissue, and that could be in the lung, that could be in lymph nodes or other parts of the body and that tissue that’s sampled is first sent to my colleagues in pathology.  

And they’re a group of doctors who look at tissues underneath the microscope and try to identify what those are. And based on that initial pathology analysis, we can identify usually pretty straightforward, what is the type of cancer that they see under the microscope.  

And so, in very general terms there are non-small cell lung cancers, there is a group called small cell lung cancers, and there’s also a group called neuroendocrine cancers as well. Oftentimes, times we’re able to differentiate these types of tumors, these types of lung cancers based on how different markers show up, and these are called stains. 

And these stains can differentiate non-small cell between adenocarcinoma versus squamous cell carcinoma. And then they can also help differentiate small cell lung cancer. And then, of course, they can also help to identify if this is a neuroendocrine tumor. 

Katherine Banwell:

Today we’re going to focus on non-small cell lung cancer. Are there specific tests that patients should ask their doctor for following a diagnosis? 

Dr. Erin Schenk:

Absolutely, and I think it’s sometimes helpful to understand what are all the pieces of information I need when I first meet a patient to make decisions about treatments? So, we just went over the histology or another word, the pathology, what does the cancer look like underneath – under the microscope? That can help and that’s one of the pieces, understanding what type of non-small cell lung cancer is present. 

Additional information that’s needed includes certain tests, and you might hear say like, molecular testing or sequencing.  

Those pieces of information can be really important for treatment selection. So, whether there’s a diagnosis of adenocarcinoma or squamous cell lung cancer, we always try to know the PD-L1 status. And that’s actually a surface marker that’s present on the outside of the cancer cells and is able to help us select immunotherapy treatments as appropriate.  

Oftentimes, patients with lung adenocarcinoma will get further sequencing of the tumor itself. And again, you might hear of this called molecular testing or next-generation sequencing, NGS. There are a lot of terms we use for it, but fundamentally, what we’re trying to do is understand the vulnerabilities of the cancer cells. 

And these vulnerabilities can be identified by these molecular tests. They often are able to recognize mutations or fusions or genetic changes within the cancer cells that are present. This is critically important, because we have a whole number of oral targeted therapies that can go after these mutations or alterations, and in other words, they go after the vulnerability in the cancer cells. That’s the adenocarcinoma histology.  

That’s the majority of non-small cell lung cancer diagnoses but I think also if you have been told your diagnosis is of squamous lung cancer, classically we don’t often think of those driver alterations or those fusions or mutations that I just spoke about. But I think it’s also quite important for patients in that situation to also undergo molecular testing.  

As we learn more and more, sometimes those squamous lung cancers can also bear those same alterations. Not to the same frequency, but they can be present, and I think it’s important as you’re thinking about a patient to try to understand what are all the tools I have for them to do that sequencing just to make sure you’re not missing something. So, that’s a really in-depth look to molecular testing.  

I’d like to transition to some of the other tests that would be necessary to help put that molecular testing in context. Another important piece is something called staging.  And staging is a way to determine if the lung cancer has traveled elsewhere in the body. 

Sometimes it can be involved in the lymph nodes of the middle of the chest. Sometimes it can go outside the chest. For example, to the bones or the liver or the brain, and understanding that information, understanding that lay of the land before we start treatment, is really important, not only for treatment selection, like the treatments, the medicines I would give as a medical oncologist.  

But also, in thinking about which other colleagues of mine who help take care of patients with lung cancer should I also involve in some of these treatment decisions. So, staging can often involve CT scans of the chest, abdomen, pelvis. A PET scan can be done. As well as an MRI of the brain. 

Katherine Banwell:

Dr. Schenk, I just want to confirm that you’ve been speaking about molecular testing, that’s the same as biomarker testing, right? 

Dr. Erin Schenk:

Exactly. Exactly. 

Katherine Banwell:

And how is it performed? 

Dr. Erin Schenk:

So, biomarker testing, molecular testing, NGS, there’s a whole range of synonyms we use, that is done primarily on the tumor tissue.  

So, the first test that usually comes back is a marker on the cancer cell. 

That’s PD-L1. That is an IHC test that is able to be done pretty quickly and we’re able to have a turnaround time of just a few days to understand that first biomarker. But the PD-L1 status does not make sense unless we have all of the other information to get the best context, the best understanding of the tumor and what drives the tumor. That additional testing is actually the next-generation sequencing where the genetic material of cancer cells, the DNA and RNA is sequenced in a laboratory to look for those mutations or fusions or other alterations that can drive the cancer cells. And again, it helps me identify additional vulnerabilities in the cancer cells to allow me to pick the optimal therapy for the patient in front of me.  

The tissue testing is the gold standard and we try to get all of our answers from the tissue. Sometimes we’re also able to get additional information from the blood, and that’s what’s called a liquid biopsy. Cancer cells – in some patients, cancer cells shed their genetic material into the bloodstream.  

And these specialized tests are able to pick up that genetic material, have the sequencing done on that, and then report back to me about what may or may not be found.  

Now, as I mentioned, not all of lung cancers shed this information into the blood, so it’s not – if the blood does not reveal an answer or information, that’s – we still need to look closer at the tissue, but occasionally if the blood reveals certain alterations, that can be acted upon, and we don’t have to wait for the tissue testing. 

I think one of the challenges that I absolutely sympathize with their biomarker or molecular testing is that it can take a series of weeks to really get all of the information necessary to make the best choice for the patient in front of us.  

And I have a – I have a saying I like to share with patients that is really important and I think really fundamental to the treatment choices for patients with lung cancer and that is, it’s better to get started on the right treatment rather than the fast one, and that’s true. We know through a series of clinical trials that if I were to start a patient on a treatment that wasn’t appropriate to their biomarkers I actually hurt them. So, I actually reduce how well their later therapies will work. 

And so, it’s a tough wait and I anxiously wait with all of my patients but it’s a really important – it’s really important to get all of that information together. 

Katherine Banwell:

Well, would the cancer change dramatically over a period of three or four weeks?  

Dr. Erin Schenk:

That’s it, you know, that’s a question I hear a lot from patients, and, again, to empathize with the agony of waiting, it’s hard to wait but I can tell you as a doctor who’s taken care of many, many patients with lung cancer the weeks do not make a difference in terms of will have – will it hurt me? So, it will not in general it does not hurt to wait. It’s better to get started on the right treatment because the right treatment has the highest chance of being effective. 

So, the two to three weeks very rarely in my experience has that changed a situation for a patient, but that’s also why we frequently do the liquid biopsy testing at the same time as the tissue testing, because we too want to try to get the answer as quick as possible. So, we try to exhaust all of the routes that we have to get the answer that we need for our patients. 

Katherine Banwell:

What about the latest advances, is there anything in lung cancer testing that patients should know about?  

Dr. Erin Schenk:

Yes, absolutely. I think more and more we’re using these liquid biopsies in different situations for patients with lung cancer. So, Katherine, you and I have mostly been talking about patients who’ve been diagnosed with metastatic disease or a disease that’s been spread outside of the lungs. The liquid biopsy testing, though we’re starting to use in patients who have tumors we can remove with surgery or tumors we can try to cure with a combination of chemotherapy and radiation therapy. 

And we’re using more as a marker of response, and what I mean by that is let’s say someone with a cancer that can be surgically resected or removed by surgery, we can check their liquid biopsy. And if we see a marker in their liquid biopsy, we can then follow that over time in conjunction with scans to try to understand is the cancer – you know, with all the information we can, is the cancer completely gone or are we starting to see that marker again? Do we need to think about doing different scans or different tests to look for a potential area of recurrence of the cancer? 

Katherine Banwell:

What sort of questions should patients be asking about their test results? 

Dr. Erin Schenk:

Uh-huh. I think there are – I think the primary question is “Have you sent my tissue for biomarker testing?” 

And this is true – in my opinion, this is true regardless of the stage of diagnosis, again in the non-small cell lung cancer space, and that’s because we are starting to use some of our targeted therapies as well as our immunotherapies in patients with cancer that can be resected by surgery or maybe would get chemotherapy and radiation therapy. So, these biomarkers are also important in that decision-making for patients that have an earlier stage of disease. And so, I think the first question is, “Has my tissue been sent for biomarker testing?” because I think that’s a part as a necessary part of care given the advances that we’ve made.  

That’s the first question, two, “When do you expect the results? When did it get sent off?” and then three, you know once that has been sent off and whether that’s tissue testing, liquid biopsy, or both, talking with your doctor and your team about what it means.  

How they incorporate this data into your treatment decisions, and then occasionally, asking about did they get all the information they need? Because while we’ve been able to do this biomarker testing for lung cancer for years now, you know, no test is perfect and sometimes cancer cells aren’t the best material to start with when you’re trying to get a really definitive answer.  

So, occasionally patients might need to be biopsied again to really and truly get the full spectrum of information necessary prior to making treatment decisions.  

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

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Thriving With AML | Advice for Setting Goals and Making Treatment Decisions from Patient Empowerment Network on Vimeo.

When facing an acute myeloid leukemia (AML) diagnosis, treatment decisions may feel overwhelming. AML specialist Dr. Alice Mims shares expert guidance for setting treatment goals with your team, advice for making care decisions, and explains how tests results may impact choices.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

See More from Thrive AML

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Transcript:

Katherine Banwell:

One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients, I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you.  

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan? 

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah, most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patients’ age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next-generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care? 

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse.  

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team.  

How Can You Access Personalized Medicine for Endometrial Cancer?

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How Can You Access Personalized Medicine for Endometrial Cancer? from Patient Empowerment Network on Vimeo.

How can endometrial cancer patients access the most personalized treatment approach for their individual disease? This animated video reviews key treatment considerations, the impact of biomarker test results on therapy options, and advice for engaging in care decisions. 

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Endometrial Cancer Treatment Decisions | Factors That Impact Your Options

Transcript:

Endometrial cancer research is evolving quickly, leading to targeted treatment approaches and helping patients access more personalized care.   

So, what is personalized medicine? Personalized medicine – also called precision medicine – is a type of care that is based on the genetic makeup and individual characteristics of a patient’s disease.  

This information is gathered using biomarker testing, which identifies key markers such as genes, proteins, or other molecules in a sample of tissue, blood, or other bodily fluid. The results of this testing can give a more detailed picture of the tumor’s type, aggressiveness, and may help predict how the cancer will behave. 

The test results can also identify which treatment approach may be most effective, through the presence of certain molecular markers.  For example, if biomarker testing results reveal that a tumor has either high microsatellite instability (MSI high) or mismatch repair defects (dMMR), an endometrial cancer patient may benefit from immunotherapy.  

Or, if the results show the HER-2 or mTOR mutation, this could indicate that the disease may respond well to a targeted therapy. And the presence of estrogen or progesterone receptors in a patient’s tumor may suggest hormonally targeted therapies may be beneficial. 

In addition to biomarker test results, other factors that physicians consider when recommending a treatment approach include:  

  • A patient’s age, overall health, and any pre-existing conditions. 
  • The type, stage, and grade of endometrial cancer.
  • And the patient’s preference. 

When considering treatment, patients should discuss the pros and cons of each option with their doctor. And they should review potential side effects, understand how the treatment is administered, and how the therapy may impact their lifestyle.  

So, what steps can YOU take to access personalized care? 

  • Find out if your doctor has experience treating endometrial cancer. Consulting a specialist or getting a second opinion can help confirm your diagnosis and treatment plan. 
  • Next, request all essential testing, including biomarker testing, and discuss how the results may impact prognosis and therapy options.  
  • You should also ensure that you understand ALL of the treatments available to you – including clinical trials.
  • And, make sure to have a friend or loved one present during discussions, so you can talk about the information later and feel confident in your decisions.
  • Finally, don’t hesitate to share your opinion and ask questions about available options. Remember, YOU should be at the center of your endometrial cancer care. 

To learn more about endometrial cancer and to access tools for self-advocacy, visit powerfulpatients.org/endometrial  

Why Test Results Matter | Accessing Personalized Non-Small Cell Lung Cancer Treatment

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Why Test Results Matter | Accessing Personalized Non-Small Cell Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

Can test results affect non-small cell lung cancer treatment options? Dr. Erin Schenk reviews essential lung cancer testing, discusses how the results may influence treatment approaches, and explains why it’s important for patients to take an active role in their care and treatment choices.

Dr. Erin Schenk is a medical oncologist, lung cancer researcher, and assistant professor in the division of medical oncology at the University of Colorado Anschutz Medical Center.

Download Program Resource Guide

See More From INSIST! Lung Cancer

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An Expert Explains Predictive Biomarker Testing for Lung Cancer

An Expert Explains Predictive Biomarker Testing for Lung Cancer

 Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing

 What Biomarkers Affect Lung Cancer Care and Treatment

What Biomarkers Affect Lung Cancer Care and Treatment?

Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss the latest advances in lung cancer including the role of genetic testing and how this may affect treatment options. 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. Erin Schenk. Dr. Schenk, welcome, would you please introduce yourself? 

Dr. Erin Schenk:

And thanks so much, Katherine. I’m Dr. Erin Schenk. I’m a medical oncologist at the University of Colorado and I have a great position where I’m able to take care of patients with lung cancer in the clinic and also, do laboratory-based research on new and different therapies for lung cancer. Thanks so much for having me. 

Katherine Banwell:

That’s so great. Oh, I’m so glad you were able to join us today. Because this program is part of our Insist series which empowers patients to insist on better care. Can you tell us why you think it’s important for patients to speak up and engage in their lung cancer care decisions?  

Dr. Erin Schenk:

Absolutely, and I think as a physician it’s important not only to partner with patients but as well as their loved ones and their caregivers who help navigate this diagnosis of lung cancer. There are some diagnoses in the world, cancer being one of them and lung cancer especially that can turn everything upside down. So, it completely changes your world. Suddenly the life as you’ve been living it, the plans you had they all have to be paused or halted in some way to get care for the lung cancer diagnosis.  

One of the – and one of the really hopeful parts about being a doctor who cares for patients with lung cancer is just the speed of the advancements and the speed of the changes in the treatment options that we have for patients diagnosed with really any type of lung cancer.  

And so, I think it’s really important when you’re meeting with your team and you’re talking with your cancer doctor to really try to understand what is the information that they use to make some of these decisions or referrals on your behalf? And also, think about, is there an opportunity for me to get another opinion about what might be the best options? 

Katherine Banwell:

Thank you for that Dr. Schenk, that’s helpful as we begin our discussion today. I’d like to start with some basics. What are the various subtypes of lung cancer, and how are they identified?  

Dr. Erin Schenk:

Absolutely. So, there are a number of different subtypes of lung cancer that are important for us to identify, because it helps to stratify or helps to select the right treatment approaches for a patient. So, usually when someone is diagnosed with lung cancer there was a scan done at some point that noticed a mass or masses in the body. 

What happens next is a biopsy happens where a needle is used to sample the tissue, and that could be in the lung, that could be in lymph nodes or other parts of the body and that tissue that’s sampled is first sent to my colleagues in pathology.  

And they’re a group of doctors who look at tissues underneath the microscope and try to identify what those are. And based on that initial pathology analysis, we can identify usually pretty straightforward, what is the type of cancer that they see under the microscope.  

And so, in very general terms there are non-small cell lung cancers, there is a group called small cell lung cancers, and there’s also a group called neuroendocrine cancers as well. Oftentimes, times we’re able to differentiate these types of tumors, these types of lung cancers based on how different markers show up, and these are called stains. 

And these stains can differentiate non-small cell between adenocarcinoma versus squamous cell carcinoma. And then they can also help differentiate small cell lung cancer. And then, of course, they can also help to identify if this is a neuroendocrine tumor. 

Katherine Banwell:

Okay. Thank you so much for explaining that. Today we’re going to focus on non-small cell lung cancer. Are there specific tests that patients should ask their doctor for following a diagnosis?  

Dr. Erin Schenk:

Absolutely, and I think it’s sometimes helpful to understand what are all the pieces of information I need when I first meet a patient to make decisions about treatments? So, we just went over the histology or another word, the pathology, what does the cancer look like underneath – under the microscope? That can help and that’s one of the pieces, understanding what type of non-small cell lung cancer is present. 

Additional information that’s needed includes certain tests, and you might hear say like, molecular testing or sequencing. Those pieces of information can be really important for treatment selection. So, whether there’s a diagnosis of adenocarcinoma or squamous cell lung cancer, we always try to know the PD-L1 status. And that’s actually a surface marker that’s present on the outside of the cancer cells and is able to help us select immunotherapy treatments as appropriate.  

Oftentimes, patients with lung adenocarcinoma will get further sequencing of the tumor itself. And again, you might hear of this called molecular testing or next-generation sequencing, NGS. There are a lot of terms we use for it, but fundamentally, what we’re trying to do is understand the vulnerabilities of the cancer cells. 

And these vulnerabilities can be identified by these molecular tests. They often are able to recognize mutations or fusions or genetic changes within the cancer cells that are present. This is critically important, because we have a whole number of oral targeted therapies that can go after these mutations or alterations, and in other words, they go after the vulnerability in the cancer cells. That’s the adenocarcinoma histology.  

That’s the majority of non-small cell lung cancer diagnoses but I think also if you have been told your diagnosis is of squamous lung cancer, classically we don’t often think of those driver alterations or those fusions or mutations that I just spoke about. But I think it’s also quite important for patients in that situation to also undergo molecular testing.   

As we learn more and more, sometimes those squamous lung cancers can also bear those same alterations. Not to the same frequency, but they can be present, and I think it’s important as you’re thinking about a patient to try to understand what are all the tools I have for them to do that sequencing just to make sure you’re not missing something. So, that’s a really in-depth look to molecular testing.  

I’d like to transition to some of the other tests that would be necessary to help put that molecular testing in context. Another important piece is something called staging. And staging is a way to determine if the lung cancer has traveled elsewhere in the body.  

Sometimes it can be involved in the lymph nodes of the middle of the chest. Sometimes it can go outside the chest. For example, to the bones or the liver or the brain, and understanding that information, understanding that lay of the land before we start treatment, is really important, not only for treatment selection, like the treatments, the medicines I would give as a medical oncologist.  

But also, in thinking about which other colleagues of mine who help take care of patients with lung cancer should I also involve in some of these treatment decisions. So, staging can often involve CT scans of the chest, abdomen, pelvis. A PET scan can be done. As well as an MRI of the brain. 

Katherine Banwell:

Dr. Schenk, I just want to confirm that you’ve been speaking about molecular testing, that’s the same as biomarker testing, right?  

Dr. Erin Schenk:

Exactly. Exactly.  

Katherine Banwell:

And how is it performed? 

Dr. Erin Schenk:

So, biomarker testing, molecular testing, NGS, there’s a whole range of synonyms we use, that is done primarily on the tumor tissue.   

So, the first test that usually comes back is a marker on the cancer cell. 

That’s PD-L1. That is an IHC test that is able to be done pretty quickly and we’re able to have a turnaround time of just a few days to understand that first biomarker. But the PD-L1 status does not make sense unless we have all of the other information to get the best context, the best understanding of the tumor and what drives the tumor. That additional testing is actually the next-generation sequencing where the genetic material of cancer cells, the DNA and RNA is sequenced in a laboratory to look for those mutations or fusions or other alterations that can drive the cancer cells. And again, it helps me identify additional vulnerabilities in the cancer cells to allow me to pick the optimal therapy for the patient in front of me. 

The tissue testing is the gold standard and we try to get all of our answers from the tissue. Sometimes we’re also able to get additional information from the blood, and that’s what’s called a liquid biopsy. Cancer cells – in some patients, cancer cells shed their genetic material into the bloodstream.  

And these specialized tests are able to pick up that genetic material, have the sequencing done on that, and then report back to me about what may or may not be found.  

Now, as I mentioned, not all of lung cancers shed this information into the blood, so it’s not – if the blood does not reveal an answer or information, that’s – we still need to look closer at the tissue, but occasionally if the blood reveals certain alterations, that can be acted upon, and we don’t have to wait for the tissue testing. 

I think one of the challenges that I absolutely sympathize with their biomarker or molecular testing is that it can take a series of weeks to really get all of the information necessary to make the best choice for the patient in front of us.  

And I have a saying I like to share with patients that is really important and I think really fundamental to the treatment choices for patients with lung cancer and that is, it’s better to get started on the right treatment rather than the fast one, and that’s true. We know through a series of clinical trials that if I were to start a patient on a treatment that wasn’t appropriate to their biomarkers I actually hurt them. So, I actually reduce how well their later therapies will work. 

And so, it’s a tough wait and I anxiously wait with all of my patients but it’s a really important – it’s really important to get all of that information together. 

Katherine Banwell:

Well, would the cancer change dramatically over a period of three or four weeks? 

Dr. Erin Schenk:

That’s it, you know, that’s a question I hear a lot from patients, and, again, to empathize with the agony of waiting, it’s hard to wait but I can tell you as a doctor who’s taken care of many, many patients with lung cancer the weeks do not make a difference in terms of will have – will it hurt me? So, it will not in general it does not hurt to wait. It’s better to get started on the right treatment because the right treatment has the highest chance of being effective. 

So, the two to three weeks very rarely in my experience has that changed a situation for a patient, but that’s also why we frequently do the liquid biopsy testing at the same time as the tissue testing, because we too want to try to get the answer as quick as possible. So, we try to exhaust all of the routes that we have to get the answer that we need for our patients. 

Katherine Banwell:

What about the latest advances, is there anything in lung cancer testing that patients should know about? 

Dr. Erin Schenk:

Yes, absolutely. I think more and more we’re using these liquid biopsies in different situations for patients with lung cancer. So, Katherine, you and I have mostly been talking about patients who’ve been diagnosed with metastatic disease or a disease that’s been spread outside of the lungs. The liquid biopsy testing, though we’re starting to use in patients who have tumors we can remove with surgery or tumors we can try to cure with a combination of chemotherapy and radiation therapy. 

And we’re using more as a marker of response, and what I mean by that is let’s say someone with a cancer that can be surgically resected or removed by surgery, we can check their liquid biopsy. And if we see a marker in their liquid biopsy, we can then follow that over time in conjunction with scans to try to understand is the cancer – you know, with all the information we can, is the cancer completely gone or are we starting to see that marker again? Do we need to think about doing different scans or different tests to look for a potential area of recurrence of the cancer? 

Katherine Banwell:

What sort of questions should patients be asking about their test results? 

Dr. Erin Schenk:

I think the primary question is “Have you sent my tissue for biomarker testing?” 

And this is true – in my opinion, this is true regardless of the stage of diagnosis, again in the non-small cell lung cancer space, and that’s because we are starting to use some of our targeted therapies as well as our immunotherapies in patients with cancer that can be resected by surgery or maybe would get chemotherapy and radiation therapy. So, these biomarkers are also important in that decision-making for patients that have an earlier stage of disease. And so, I think the first question is, “Has my tissue been sent for biomarker testing?” because I think that’s a part as a necessary part of care given the advances that we’ve made.  

That’s the first question, two, “When do you expect the results? When did it get sent off?” and then three, you know once that has been sent off and whether that’s tissue testing, liquid biopsy, or both, talking with your doctor and your team about what it means.  

How they incorporate this data into your treatment decisions, and then occasionally, asking about did they get all the information they need? Because while we’ve been able to do this biomarker testing for lung cancer for years now, you know, no test is perfect and sometimes cancer cells aren’t the best material to start with when you’re trying to get a really definitive answer.  

So, occasionally patients might need to be biopsied again to really and truly get the full spectrum of information necessary prior to making treatment decisions.  

Katherine Banwell:

Yeah, great suggestions. Great ideas, thank you. We’re hearing the term personalized medicine a lot these days. Would you define the term for our audience? 

Dr. Erin Schenk:

Absolutely, and I think the treatment of non-small cell lung cancer is one of the poster childs for children – for personalized medicine because based on the result of the biomarker testing that’s what drives my choice of therapy because the biomarkers help to tell me what is this cancer most likely to be vulnerable to and that in my mind that’s a wonderful application of the promise of personalized medicine.   

Katherine Banwell:

Okay. Let’s move on to treatment now, Dr. Schenk. Would you walk us through the current treatments being used to treat non-small cell lung cancer? 

Dr. Erin Schenk:

Absolutely, and there are a broad range of options, and thankfully we have so many choices in how to best help patients. And it’s often why visiting with a center that sees a lot of patients with lung cancer can be beneficial so that you have all of the parties at the table that need to be there as we’re making these treatment decisions. So, I would start thinking about patients with early-stage disease. Often surgery if tumors are small enough and there’s not you know, no lymph nodes are involved with the cancer and it’s not anywhere else.  

Sometimes surgery is all that patients might need in terms of their treatment. Those are for patients with smaller tumors and really early-stage disease. As we move forward in the stages, meaning going from stage one to stage two, so a little bit bigger of a tumor, lymph nodes might be involved.  

That’s when really the multi-disciplinary approach happens, and what I mean by that is for example, at my institution where people like me, medical oncologists, radiation oncologists, and surgeons all sit down together to talk about a patient, their scans, you know, what is their health status, what is their biomarker testing, to try to come together to form a treatment approach. And so, at our institution, you know, frequently in stage two to stage three tumors based on biomarker testing we either select upfront surgery followed by chemotherapy followed by sometimes targeted therapies or TKIs.  

Those are the medicines, the TKI, those are the medicines that are really dependent on the presence of biomarker testing. So, the biomarkers often tell us for example if there’s an EGFR mutation. If that’s present then I would use an EGFR TKI, for example. 

But if those biomarkers don’t show a alteration where I have TKI to use, then we frequently are giving patients chemotherapy plus immunotherapy before surgery. This approach is called a neoadjuvant chemoimmunotherapy approach, and it’s one of the newer changes to lung cancer care within the past year that I think really is going to have a positive impact on outcomes for patients with lung cancer.   

So, just again in broad strokes, and then as we move into stage three patients where we can’t resect the tumor, that’s where we give chemotherapy medicines plus radiation therapy. Oftentimes followed by immunotherapy and then when patients have disease that spread outside of the chest, outside of the lungs, the metastatic setting or stage IV, that’s when we think about the whole host of therapies available through medical oncology, systemic therapies is another way to call them.  

And there we think about immunotherapy-based treatments plus or minus chemotherapy or we think about targeted therapy-based approaches with those TKIs. And again, it’s all based on those molecular markers, those biomarkers. 

Katherine Banwell:

Do clinical trials play a role in lung cancer treatment? 

Dr. Erin Schenk:

Clinical trials are incredibly important for the treatment of lung cancer. These are the tests and the procedures that we do that have continuously advanced our ability to care for patients with lung cancer. You know, it was clinical trial data that helped us get alerted to doing chemotherapy and immunotherapy before surgery really can help patients do better. And similarly, clinical trials have helped us define when do we use TKIs or targeted therapies. 

So, I think that’s another great question to ask your team of, “Based on all of the information you know about me and my cancer are there clinical trials options that are available here where I’m at or ones that are really interesting or appealing elsewhere that might be worthwhile for me to consider?” So, clinical trials are a critical part of how we help patients do better.  

Katherine Banwell:

Personalizing therapy involves taking into account a number of patient factors. What should be considered when deciding on a treatment regimen for a given patient?   

Dr. Erin Schenk:

Yes. That’s a great question and one that is really important in formulating a treatment plan. So, some patients because of their health status, for example, aren’t able to undergo surgery, and that happens. And so, occasionally sort of their health status maybe their lungs don’t work as well as they used to or the heart doesn’t pump as well as it used to. 

You know, those sorts of health concerns can help us tailor and personalize treatments to what would be the most – the safest but also the most effective approach. Occasionally patients have another long-term chronic disease where using immunotherapy might be more dangerous than helpful because they’re sometimes autoimmune diseases.  

Especially ones that affect the brain, so for example multiple sclerosis can be one of those or disease that affect the lungs, you know, interstitial lung diseases. Those would put a patient at great risk of receiving immunotherapy, but outside of the health status, it’s also important I think to talk about what your preferences are as a patient as well.  

Because sometimes we will come to you and say, “Here are these multiple different choices and what’s important to you or maybe what you’re worried about or what you’re concerned about are considerations that we want to hear about and understand so that we can talk you through the process and help make some of these decisions.” You know, for example, if you’re receiving chemotherapy plus radiation together for your cancer care that can be a huge time commitment.  

What I mean by that is when patients get radiation in certain circumstances, that can be once a day every day, Monday through Friday for six weeks at a time and sometimes patients have challenges with transportation. Or sometimes they have you know, challenges balancing a job or childcare or other things like that. So, these are all part of the – just part of bringing it all together and putting together a treatment plan that makes sense for what we understand about the lung cancer itself, but also what we understand about you as our patient. 

You know, how can we make changes or make suggestions that would best fit for you and your needs? 

Katherine Banwell:

You’ve brought up some really good points and of course, patients should be involved in these decisions. If a patient is feeling uncomfortable with their care plan, why do you think it’s important for them to speak up? 

Dr. Erin Schenk:

In my experience, when people are worried about certain things or they say they definitely don’t want this therapy it’s because they have seen other loved ones or family members suffer because of that particular type of treatment in the past. And I think bringing up those concerns can be helpful for me as someone’s doctor to talk them through, okay, this is what chemotherapy looks like. This is what we do to help reduce your side effects.  

These are the resources we have to support you through treatment if any of these side effects come about and I think I also impress upon them that receiving treatment is ultimately their decision now. My bias of course, I think we can help patients quite a bit with their treatments, but I think it’s also important to recognize you know, they have autonomy to say no at any point in time. And I think just acknowledging those fears, acknowledging those concerns, putting together a plan you know, before any of those potential worrisome side effects happen can be really powerful to help reduce some of the stress and worry around treatment. 

Katherine Banwell:

Dr. Schenk, when should patients consider a second opinion or even consulting a specialist? 

Dr. Erin Schenk:

I think any time it’s appropriate. We – at our institution, we’re one of the main lung cancer centers that – you know, within several hundred miles, so we frequently see patients and sometimes it’s just to check in and say you know, the patient says, “Here’s what my team has started me on. You know, what do you think should be the next approach?” and we talk about that, but really anytime I think is appropriate for reaching out for another set of eyes to look at things. I would say perhaps some of those most critical times would be prior to treatment starts especially if – yeah, I would say prior to starting a treatment with that new diagnosis.  

That would be a really critical time because often again, sometimes once we start down a treatment path, we’re in some ways we’re committed, but if that maybe isn’t the optimal treatment path based on, you know, the tumor and the biomarkers and the patient preference starting on that less optimal treatment path could potentially hurt patients in the long run. So, I would say at – you know, potentially at diagnosis when a treatment course is recommended and then if there is a need to change treatments.  

So, for example, especially in the metastatic setting there are certain therapies widely available. People are very familiar with them, can start them no problem, but when those treatments stop being beneficial that might be a time to also meet with a specialist or go to a lung cancer center of excellence to get their opinions on what to do next.  

Katherine Banwell:

You know, one thing patients are often concerned about is the financial aspect, the financial burden that is involved in their treatment care. How do they deal with that? Are there resources available for them? 

Dr. Erin Schenk:

There can be and this definitely can vary based on what treatment you’re being given and where you are, at what institution and what state you’re being treated at since resources are different. But for example, the targeted therapies or the TKIs I made reference to earlier, those can have some significant out-of-pocket costs and most of the,  if not all of the manufacturers of those various TKIs have patient assistance programs that help to reduce the out-of-pocket costs for those specific medicines.  

When I prescribe a TKI for a patient often what’s part of that is a prior authorization to try to understand what’s the out-of-pocket cost for the patient and then kind of get on top of whether or not we need to apply for patient assistance to help pay for the cost of that medication. So, that’s one way that we can help. 

I think, in again, this is specific to my institution and our clinical practice, but we often have – we work very closely with other cancer doctors in the community. So, if traveling to our site is a major burden we can usually have them visit with a oncologist who’s close to them so there’s less travel, there’s less costs in you know gas and staying somewhere. But they still can be connected with us. So, while they can get most of their care under a doctor that’s closer to them, every so often they come back and see me and just talk about how things are going and what you know might be worthwhile to consider down the road.  

And I would also recommend that if there are other costs or concerns you know, kind of above and beyond these things that we’ve touched on, connecting with a social worker through the cancer center can be helpful in dealing with paperwork for disability or retirement or sometimes connecting to resources if there’s a childcare need. 

Or you’re caring for a spouse and you need additional help at home. You know all of the different burdens that are present in life that just get magnified with a cancer diagnosis and you know, we can – there’s usually a really big attempt to try to find a way to help figure out navigating those so that you can get the care you need.  

Katherine Banwell:

Yeah. Before we close, Dr. Schenk, I’d like to get your final thoughts. What would you like to leave the audience with? Are you hopeful? 

Dr. Erin Schenk:

Yes. There are tremendous – there has been tremendous growth and change in the practice in how we treat patients with lung cancer, even just in the past handful of years and it’s made marked improvements in how well people do and for how long they do well. 

And that – you know that trajectory I anticipate continuing based on the clinical trials I’ve been involved with as well as the data I hear about from other clinical trials thinking about new and different medicines that we could use in the diagnosis of lung cancer. As well as applying some of the medicines we already have in different ways and different situations you know, to help better control the cancer or help even increase the cure rate in certain situations.  

So, I think there are a number of reasons to be hopeful and if you visit with your team of doctors and that you don’t get that sense of hope or you don’t hear about all the different ways that they can help you, you know that might be a time to really think about, “Perhaps I need to get a second opinion and hear about some of these developments or some these other ways that potentially I could be treated with my new diagnosis of lung cancer.”   

So, I think there are a lot of reasons to be hopeful. Lung cancer, of course, is still a serious life-changing diagnosis, but there are ways we can help regardless of what the stage is or where you’re at in life. I think there are opportunities for us to still help you. 

Katherine Banwell:

It sounds promising, Dr. Schenk. Thank you so much for taking the time to join us today. 

Dr. Erin Schenk:

Absolutely. Thank you for the invitation.  

Katherine Banwell:

And thank you to all of our partners. To learn more about lung 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.   

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

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

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

Download Resource Guide

See More From INSIST! Prostate Cancer

Transcript:

Katherine:

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

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

Dr. Gao:

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

Katherine:

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

Dr. Gao:

I’m happy to be here.  

Katherine:

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

Dr. Gao:

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Katherine:

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

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

Dr. Gao:

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

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

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

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

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

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

Download Resource Guide

See More From INSIST! Prostate Cancer

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What Are Current Prostate Cancer Treatment Options?

Transcript:

Katherine:

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

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

Dr. Gao:

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

Katherine:

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

Dr. Gao:

I’m happy to be here.  

Katherine:

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

Dr. Gao:

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

How are some of these symptoms managed?  

Dr. Gao:

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Katherine:

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

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

Dr. Gao:

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

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

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

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

Katherine:

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

Dr. Gao:

You’re welcome. Thanks for having me. 

Katherine:

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

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

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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?

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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.
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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

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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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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.

Expert Advice | Shining a Light on Equitable AML Care

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Expert Advice | Shining a Light on Equitable AML Care from Patient Empowerment Network on Vimeo.

While treatment options are improving, there are still many factors impacting equitable care for AML patients. Dr. Ann-Kathrin Eisfeld shares advice for improving research and clinical trials for underserved AML populations.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

See More From INSIST! AML

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How Does the Presence of Molecular Testing Affect AML Care?

Transcript:

Katherine Banwell:

Dr. Eisfeld, we’ve covered a lot of information related to AML care. As a researcher, what other topics are currently top of mind for you in the field of AML? What are you passionate about? 

Dr. Eisfeld:

Again, so many parts. I think there are probably three main things that I’d like to name. And I think about it as a little bit outside the box. Most of what we know about AML, we have become so much better. It’s because we have been studying patients who were treated over the past decades on clinical trials and very often here in the U.S. or in Europe.  

But all clinical trials have a bias in that most of them have been done A) on patients who are younger than the age of 60. And B) fewer patients of other races and ethnicities included. And had patients not included that have AML, for example, not only in the bone marrow but on extramedullary sites – how we call it – up to 10 percent of their patients. And also, very often have not been done on very old patients where the AML is very common. So, all the patients – patients from other race, ethnicities, or underrepresented minorities, and patients who present with extramedullary disease are currently in my – underserved.  

And these are exciting areas and opportunities of research and of active clinical practice. Because those are the patients we need to include if it’s possible now to include them in clinical trials. 

If there are no trials available, then make sure any other additional molecular testing it done to understand them better and to advance our disease knowledge that we make sure that we can give the best possible care.  

I think that the most important part is to get the molecular testing, and to enroll into clinical trials, and then to very often biobanking.  

Why am I saying that is because our knowledge AML comes from patients who donated some tissue so that we could learn – researchers decades ago could learn about the genes. We know that leukemias differ so much in between patients.  

So, I am worried that we are yet missing out on potentially important genes that need to be discovered and where we could develop docs for. This will only be possible with these additional testing. 

 The second part is to really consider going to larger treatment and larger treatment cancer center. And there are support systems in case that can help in here.  

And the third part is to get involved even as early as possible even if you’re not personally affected, with Be The Match – with bone marrow transplant because there’s a paucity of donors, of people of color that makes it harder for these patients to get a potentially curative treatment in here.  

We have other options now in bone marrow transplant where one can use only half-matching donors and or other availabilities. But again, that doesn’t outweigh that the bone marrow and donor registry that we need to get better at.  

And I can – there are just so many factors – such a high degree of structural racism that affects people from every corner. And I think we as physicians, as society, and everybody need to acknowledge that. And we have to make sure that we get better to, again, give every patient the best care and keep the patient in mind and see what’s right for them at the right moment.    

Katherine Banwell:

Where can patients or people who are interested find out about being a donor? 

Dr. Eisfeld:

There is the website called “Be the Match” that one can put in. This is probably the best way to get first information.  

And usually, at all the cancer sites. And sometimes, there is information at lab donation places, universities, either or the American Red Cross. Usually those places have information laid out there as well. 

MPN Essential Testing | How Results Impact Care & Treatment Options

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MPN Essential Testing | How Results Impact Care & Treatment Options from Patient Empowerment Network on Vimeo.

How could molecular testing affect MPN treatment decisions? Dr. Raajit Rampal explains the purpose of this essential testing and how the results may impact prognosis and care. 

Dr. Raajit Rampal is a hematologist-oncologist specializing in the treatment of myeloproliferative neoplasms (MPNs) and leukemia at Memorial Sloan Kettering Cancer Center in New York City. Learn more about Dr. Rampal.

 

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Transcript:

Katherine Banwell:

Let’s talk about what sort of tests should be done following an MPN diagnosis. Can you tell me about those? 

Dr. Raajit Rampal:

Yeah. Fundamental to the MPN itself, the things that we really want to know is, in most cases, a bone marrow examination is needed because that will tell us really what the disease is that we’re dealing with. It will tell us about the genetics. I strongly believe we have to be comprehensive in our genetic assessments because that does prognosticate and sometimes gives us an opportunity in terms of treatment. Chromosomal analysis. These are the basic bread and butter hematology tests we want to do from the bone marrow to really understand what the patient’s disease is. 

Beyond that, I think that particularly in patients with PV and ET, it’s important that we partner with their primary care physicians to make sure that they’ve had, for example, testing for diabetes, a recent lipid profile, any cardiovascular tests, particularly measurements of blood pressure because these things are all important in terms of an ET or PV patient’s risk of having a blood clot. So, there are, again, things that are within hematology realm but then, there are other general health things that become really important in somebody who is diagnosed with PV or ET. 

Katherine Banwell:

How often should lab tests of blood work be done? 

Dr. Raajit Rampal:

It really depends on the patient. For some patients with PV, for example, they need to have their blood checked every three weeks because they’re having frequent phlebotomies. Whereas some patients with ET could probably go forward to six months between blood tests. So, it depends on the individual. 

Katherine Banwell:

How can results of biomarker testing affect treatment choices for patients with MPNs? 

Dr. Raajit Rampal:

Great question. The genetics are becoming increasingly important in our treatment decisions. So, let’s take a simple example, which is patients with ET. Calreticulin and JAK2 and MPL are the three most common mutations that we see. But they have very different invocation. So, somebody could have a calreticulin-mutated ET and based on them having that calreticulin mutation and no other factors like no history of clotting, that patient may never need to go on a medication aside from aspirin. And even early on, it’s debatable whether or not some of these patients really need aspirin at all. 

Whereas somebody who had a JAK-2 mutant ET, our guidelines and data suggests that that person, once they reach a certain age, should probably be on medication. So, that’s kind of perhaps one of our more clearcut examples of a genetic biomarker telling us how to approach treatment. 

And then, it gets more nuanced from that and more exciting and interesting in the sense that there are mutations, for example, that occur in myelofibrosis and in patients whose disease is progressing towards leukemia, such as IDH mutations. And these are things that are now targetable with FDA-approved drugs.  

And there are now clinical trials combining JAK inhibitors and IDH inhibitors for patients who have more advanced disease who have these IDH mutations. So, you go from on one end, these genomic markers being of prognostic significance and now, on the other hand, we’re getting to a point where, in some cases, they might tell us how to best treat a patient.  

Katherine Banwell:

Dr. Rampal, should all patients diagnosed with MPNs undergo molecular testing?  

Dr. Raajit Rampal:

I strongly believe that. I think that we’ve learned so much that these tests have prognostic value. 

And in some cases, it may suggest a slightly different diagnosis. I definitely think that should be the case. 

Katherine Banwell:

What should patients be asking once they have the results? 

Dr. Raajit Rampal:

What does it mean? That’s the most basic and fundamental question. It’s one thing to get a list of mutations. But the real bread and butter question is what does this mean to the disease and my prognosis and my treatment?  Those are the key questions. 

The Importance of Molecular Testing Following an AML Relapse

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The Importance of Molecular Testing Following an AML Relapse from Patient Empowerment Network on Vimeo.

Why do you need molecular testing following an AML relapse? Dr. Sanam Loghavi emphasizes the importance of this essential testing and why it’s necessary following relapse.

Dr. Sanam Loghavi is a hematopathologist and molecular pathologist at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Loghavi.

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Transcript:

Katherine Banwell:

Unfortunately, relapse can happen following a course of treatment for AML. Should patients undergo molecular testing again before choosing another round of therapy?  

Dr. Sanam Loghavi:

100 percent yes, that is always a yes. So, like I said, at baseline there are certain recommendations and the standard of care is to perform genetic testing.  

But I cannot emphasize this enough, that AML or any cancer, for that matter, cancers tend to be smart, so they bypass the mechanisms that we try to eliminate by our targeted therapies.  

So, oftentimes the genetic landscape of disease will actually change upon relapse or what we refer to as clonal evolution, and you may hear this terminology in the literature. So, it’s very important to molecularly or genetically characterize the disease at relapse before you decide how you are going to alter the course of treatment at that point. 

Katherine Banwell:

Dr. Loghavi, what are you excited about in your research right now? 

Dr. Sanam Loghavi:

Sure. So, I’m a pathologist, so I do a lot of molecular testing, and I also do a lot of measurable residual disease testing, and measurable residual disease tends to be one of the most informative factors in the care of patients with acute myeloid leukemia. So, these are the things that we’re very excited about, again, identifying better molecular targets of therapy, being able to measure residual disease at a more sensitive level that allows us to make better informed decisions for the care of our patients. And also, again, identifying the mechanisms of how AML develops in order to be able to eliminate the disease.  

Breast Cancer Clinical Trials 201 Resource Guide

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What Does Breast Cancer Hormone Receptor Status Mean?

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What Does Breast Cancer Hormone Receptor Status Mean? from Patient Empowerment Network on Vimeo.

There are many subclassifications of breast cancer—including a patient’s hormone receptor status. Expert Dr. Jame Abraham defines hormone receptor status and explains the potential impact on breast cancer treatment outcomes.

Dr. Jame Abraham is the chairman of the Department of Hematology & Medical Oncology at Cleveland Clinic and professor of medicine at Cleveland Clinic Lerner College of Medicine. Learn more about Dr. Abraham.

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Transcript:

Katherine:

Dr. Abraham, can you please explain hormone receptor status?   

Dr. Abraham:

Yeah. So, as you know, really well, breast cancer is not one disease. It can be five, or six, or seven different diseases. There are so many subclassifications for breast cancer. So, most common type of breast cancer, especially if I can see, in postmenopausal patients, almost 70 percent of breast cancers are postmenopausal. Sorry, you can edit that out. So, in postmenopausal patients, 70 percent of breast cancers are hormone-positive, or estrogen receptor-positive – 70 percent is estrogen receptor-positive. 

So, what that means is, when, after the biopsy, the tumor is sent for a test. 

In that test, the pathologist will say – they’ll stain the tumor, and then, see if the tumor has a receptor, which is estrogen receptor, and progesterone receptor. So, as I said, 70 percent, it’s actually hormone-positive. When the tumor is estrogen receptor-positive, overall, prognosis is better. So, our prognosis is better. Second, we have better treatments, which can target that estrogen receptor-positive tumor. So, it’s a good thing when patients have hormone receptor-positive disease. Prognosis is better, we have better treatments.