How Does Genetic Testing Impact Prostate Cancer Care?

How Does Genetic Testing Impact Prostate Cancer Care? from Patient Empowerment Network on Vimeo.

Genetic testing has taken on a vital role in prostate cancer care. Expert Dr. Maha Hussain provides insight about genetics and biomarker testing, how results are used in determining treatment options, and key questions to ask to ensure the best care.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

See More From INSIST! Prostate Cancer

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Treatment Options for Advanced Prostate Cancer

Understanding Prostate Cancer Staging and Progression

How Do Genetic Mutations Impact Prostate Cancer Treatment Options


Transcript:

Katherine:

Many patients are confused about the role of genetics and biomarker testing in prostate cancer care.

For people who haven’t heard of some of these terms before, let’s go into the definitions. So, what is genomic or biomarker testing, first of all?

Dr. Hussain:

So, I think there’s one thing. Maybe I can explain because the wording can be confusing. So, there is the genetics, and there is the genomics. The genetics would be what we inherit from our families. So, this would be present in our body. The genomics testing would be to look for what the structure of the genes of the cancer itself, cancer cells itself. Now, that doesn’t mean that this was inherited. It’s just that this is a renegade, and it evolved. And that is what is going to show up.

The reason these two are important, both of them have implications potentially for treatment or perhaps clinical trials. And again, with the PARP inhibitors, the BRCA-like genes will have implications for treatment sort of for resistance cancers.

With regard to the genetics, the implications are for, again, inheritance of family and potential risk for blood relatives. Now, there are panels that are FDA-approved for the purpose of genetic testing. And the requirement or the indications right now, anybody who presents with metastatic disease or an aggressive disease and diagnosis, the recommendation is to proceed with the genetic testing, certainly counseling and testing, because there are some people who prefer not to be tested. And that’s something else.

What I tell my patients is this, even if the testing is done and it was negative for inherited genes that might put the patient family at potential higher risk, the fact that a person has prostate cancer by default puts potential, adds risks to family, to blood relatives.

And the risks aren’t just for the males with regard to prostate cancer, but certainly breast cancer, ovarian cancer, pancreatic cancer potentially, and things of that sort. So, this is where I think a patient needs to be discussing with their doctors. And certainly, there are many centers that have genetics counselor, and so that’s where I generally refer my patients to. I counsel them myself, and then refer them also for more discussions with genetics counselor.

Katherine:

What exactly are genetic mutations? And how do they impact a treatment path?

Dr. Hussain:

Well, I think, again, it’s the changes that happens in specific genes that may promote the aggressiveness of a cancer. And so, the BRCA gene is one of the oldest genes that have been identified in breast cancer. And essentially, the body regulates itself.

And when cancer cells come up and they sort of – the body no longer sustains that regulation, the genetic regulation in those cancer cells. Those cancer cells will behave the way they want to. That means that they’re going to grow faster. That means they could be resistant to treatment and things like that. And so, that’s what we check for, these alterations. And there are certain medications that would allow – and again, in prostate cancer, it’s not a lot. It’s just, as I said, right now the only things that are proven is the PARP inhibitors. This is essentially to kind of gang over the cancer cell, preventing from allowing it to repair itself so it can continue to grow.

Katherine:

Some patients may not know if they’ve received these important tests. So, for patients that aren’t all that sure, what key questions should they be asking their physician or their specialist?

Dr. Hussain:

So, I would say when it comes to the genetics testing, I believe a patient has to consent.

Because again, we live in the U.S., and this is a private matter for the patient. So, this generally has to be the case. Otherwise, depending on the institution, sometimes some tests will require for the overall testing for looking for any genetic alterations, general tumor alternation. Different centers have different things. But the patient should ask and say to their doctor, “Have my cancer genes been tested? Have my genes been tested? And if they have, what are the results?” Because we generally share with the patients once it’s been done.

The other things I should point out, some of the good things that have happened recently. Up until recently, when it comes to the tumor genomic testing, tissue was required. Nowadays, the FDA has approved blood tests that several companies now run that can actually collect blood sample and basically test it for circulating tumor cell genes there.

Now, no testing is 100 percent perfect. But in situations like patients with prostate cancer who may not have recent tissue or adequate tissue for testing, certainly doing the blood test to verify if there is anything reflective of the genes of the cancer, and that may allow for potential actionable-type treatments. Again, up until now, this is more going to apply for potential clinical trials or resistant metastatic disease.

Treatment Options for Advanced Prostate Cancer

Treatment Options for Advanced Prostate Cancer from Patient Empowerment Network on Vimeo.

What are treatment options for advanced prostate cancer? Expert Dr. Maha Hussain provides a breakdown of hormone therapy and explains how targeted therapy is used in prostate cancer care.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

See More From INSIST! Prostate Cancer

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Prostate Cancer Treatment and Research News

Understanding Prostate Cancer Staging and Progression

How to Engage in Your Prostate Cancer Treatment Decision


Transcript:

Katherine:

Now that we understand how test results can help inform a patient’s cancer and how it may behave. Let’s discuss how they can affect treatment options for men with advanced disease. First, let’s do a brief review of the treatment types currently available. There’s hormone therapy, right. What else?

Dr. Hussain:

Perhaps, it’s simpler if we focus on advanced disease, specifically metastatic disease.

So, if that’s the deal, then the backbone of treatment is hormone treatment. And it really is. We call it hormone, but technically it’s an anti-hormone. What we’re trying to do is shut down the hormonal pathway that stimulate the testes, which is the factory that makes testosterone. So, we are looking at shutting down testosterone production from the testes in order to starve the cancer.

Now, the male hormone is produced predominantly – somewhere about 95 percent of it is made by the testes, and then there are about 5 percent-ish that comes from other sources. These are, again, male hormones like the adrenal gland and so on. And there was a while ago some research – I want to say from the MD Anderson crowd, but this is two years ago – that suggested also that the tumor may start to make sort of in-house production of male hormone to support itself.

Now, having said that, again, testes continue to be the source of the majority of the male hormone. And so, historically, the first data that showed benefit was actually by surgically removing the testes, which is what we call orchiectomy or bilateral orchiectomy. And then medications began hitting the market and were evaluated in the late ’80s and then 1990s, beginning with Lupron – which by the way, in the ’80s, it was an injection that the patient had to give themselves every day, which is remarkable.

But even then, there is a personal preference by patients to go and take injections as opposed to go through surgery with orchiectomy. But still, I would say for some patients it may be an option until it ought to be discussed as an option. Then what we know is this, is because of the potential other sources for the male hormone, the concept of what we call combined androgen depravation was being evaluated.

And again, this goes back to the ’80s when the first drug was flutamide and then bicalutamide, and there are other drugs that became. And they kind of added a sprinkle, I call it, to survival. But it wasn’t dramatic, huge differences in survival. And so, generally, while we used it, everybody believed in using it. Moving forward, the drugs like abiraterone, enzalutamide, apalutamide are the three hormonal drugs that have demonstrated conclusively really an advantage in terms of prolonging life when added to the Lupron.

So, what I tell my patients is that, when it comes to hormone treatment there is really no way around it. You can delay it. Some people are exploring for some patients who don’t have a lot of cancer, maybe a couple of areas, maybe just do targeted radiation and then leave the person alone to buy them some treatment-free time.

And, to me, this is where the discussion that has to happen with the patient. What is the objective? Is the objective to kind of be ahead of the game and maximally treat the cancer with the hope of prolonging life? Or is the objective to delay treatment? And I would tell you that, with these types of conversation, nine out of 10 or 9.5 out of 10 men opt for moving aggressively up front with management. So, that’s that.

Now, the one thing I should point out, one of the trials that also was a landmark trial in this disease was the study CHAARTED, which was an intergroup clinical trial at the time it was designed, led by ECOG, and the PI was Dr. Chris Sweeney. I was part of the team that worked on the design also of the study.

And that was a trial that looked at adding docetaxel to hormone therapy, versus hormone therapy alone, to try to see if it adds something. Historically, all the chemotherapies prior to that that were added to hormone treatment for patients with newly diagnosed metastatic disease had not delivered. And docetaxel did.

However, one thing I should point out, based on that trial – and I don’t want to go into too much details for the sake of time – the patients that seemed to be benefiting were the patients that had more aggressive, more disease in their system. And so, liver metastases, lung metastases spread in the bone at different areas, not like few isolated areas in the spine or the pelvis, but much more than that.

And so, for the patients who have what we call high-volume prostate cancer based on scans – and I’m happy to explain what that means if it’s needed – these are the patients that I would offer either the docetaxel plus hormone treatment, which is the injection, or the injection plus the hormonal pills that I mentioned earlier.

Katherine:

What about targeted therapy? How is that used?

Dr. Hussain:

Okay. So, let’s begin with the molecularly targeted therapy. So, as we speak right now, for patients who have newly diagnosed metastatic disease that we call hormone-sensitive, molecularly targeted therapy is not standard of care. So, I would encourage patients who may qualify for clinical trial to be involved in those. The flipside is – we can talk about it – is that molecularly targeted therapies, specifically with PARP inhibitors have pretty much entered in the space of prostate cancer with a couple of drugs that were FDA-approved.

The other way of targeted treatment, which would be what we refer to targeted radiation, this would be a different story. This is not systemic treatment. This is a local treatment. And what is done is basically if patients do not have a lot of cancer in their body based on scans, and only certain areas, and they are starting systemic therapy, they can certainly consult with a radiation oncologist to target radiation to areas that are visible on scan. So, if somebody has a couple of, let’s say, pelvic bone lesions, maybe a lymph node, and they are already starting systemic therapy, they can consult with a radiation oncologist focal radiation. And so, that would be the general scheme.

Prostate Cancer Treatment and Research News

Prostate Cancer Treatment and Research News from Patient Empowerment Network on Vimeo.

Prostate cancer experts recently gathered at the American Society of Clinical Oncology (ASCO) annual meeting to share research updates. Expert Dr. Maha Hussain reviews clinical trial findings presented at the meeting, potential treatments for FDA approval, and credible sources for prostate cancer research information.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

See More From INSIST! Prostate Cancer

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Treatment Options for Advanced Prostate Cancer

An Update on Prostate Cancer Treatment and Research


Transcript:

Katherine:

I’d like to start by asking about developments in prostate cancer research and treatment. Experts recently gathered at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research.

So, what were the highlights from that meeting that you feel patients should know about?

Dr. Hussain:

I think probably perhaps I can focus on two major – what I would consider major highlights, and those were the results from two randomized Phase III clinical trials.

One of the trials is called the VISION trial. And the VISION trial was a Phase III randomized trial evaluating lutetium-PSMA-617 treatment in patients with metastatic castration-resistant prostate cancer. And the delightful thing about this study is that that study was positive. The PSMA story has been really going on for a few years now. And there’s the PSMA for purposes of scans, imaging, to assess the cancer. And the FDA just approved a PSMA PET imaging this year.

I think it was in May when it was approved. And that would help better define if the cancer is spread or not, and it help with the decision regarding treatment. But the second part is treatment purposes, so identifying the cancer location and trying to attack it with a specific sort of targeted attack to the tumor is really important.

And so, the FDA is currently looking at this particular agent. And I am hopeful that we will hear soon from the FDA, hopefully before the end of the year, and maybe – who knows? – maybe by summer, middle summer or end of summer. Because I do think that would be a major benchmark in there. And so, that’s one thing.

The other clinical trial that I thought was interesting from a data perspective – and for disclosure, I am one of the investigators on this study. And this was an intergroup Southwest Oncology, or SWOG, sponsored clinical trial. So, it’s a federal study that Dr. Aggarwal presented. And this was a study that was aiming at maximizing, again, the anti-tumor therapy with the use of a drug which I call is the younger brother of abiraterone.

So, abiraterone is a drug that is FDA-approved and has been around for several years right now for both castration-resistant prostate cancer and certainly hormone-sensitive metastatic disease. And so, TAK 700 (Orteronel) is a younger brother, I call it, of abiraterone (Zytiga). And one of the potential advantageous when this trial was designed was the fact that you don’t need to use prednisone. And the trial was completed. It was a national clinical trial. And what was interesting is that there is certainly what appears to be a potential benefit, but not in terms of the conclusive based on the way the study was designed.

Having said that, what I thought was remarkable is that patients who basically were only on the control arm was LHRH therapy, so this could’ve been like leuprorelin (Lupron), goserelin (Zoladex), or something like that plus bicalutamide, which is what we call combined androgen deprivation. And that was sort of like the strongest control arm we could do at the time when the trial was designed.

Remarkably, the patients who were on that arm had a median survival of basically 70 months. That’s the median. That’s the bell-shaped curve with the number in the middle. Seventy months is probably the longest ever in any other randomized trials in this disease space, in the hormone-sensitive space. So, that tells us is that men are living longer with prostate cancer, even though it’s metastatic disease; and, yes, it’s not necessarily curable, but men are living longer. And it’s a function of all of the better treatments that are supportive care and everything that was going on.

And so, the control arm, as I mentioned, was the 70.2 months. The actual experimental arm was about 81.1 months. And again, I don’t know where things will go from this. Obviously, I’m not the sponsor not the FDA. But the point here is that men are living longer, and so wellness and health become even more so important than we ever did. And as I tell my patients, every day you’ll live longer. The odds of living longer is there because of better treatments coming on.

So, to me – not to take too much time from the interview – to me, these were the two highlights: new, approved – I’m sorry, new treatment that I’m hoping will be FDA-approved and, obviously, the fact that men are living longer.

Katherine:

How can patients keep up to date on the research that’s going on?

Dr. Hussain:

I’m a bit biased, obviously. I’m a member of ASCO.

And what I would recommend to my patients is to look at the cancer.net website. The cancer.net is a website that is an ASCO-generated website specifically for patients and families to review. It is vetted. The committees are not run just by physicians, oncologists, a multidisciplinary team, but also patient representative. So, the lingo and the presentation are lay-friendly, I call it, there.

The other part I would say, the NCI website, and the American Cancer Society, the American Urological Association. I would say there’s a lot of stuff on the media. The difficulty is vetting what is sort of fake, what is not so accurate, or bias versus there. I also think that the NCCN has also some resources for patients.

And one thing I always tell patients: explore, look, but make sure that you talk to your doctor about the meanings of everything because sometimes it can be not – it could be misleading, I should say, or maybe not very clear on what the implications are.

Which Prostate Cancer Treatment Is Right for You? What You Need to Know

Which Prostate Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo

What do you need to know before deciding which treatment is best for YOUR prostate cancer? Dr. Maha Hussain discusses the role of key tests in choosing therapy, including biomarker testing, provides tips for partnering with your care team and reviews recent research news.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

Download Guide

See More From INSIST! Prostate Cancer

Related Resources

How Do Genetic Mutations Impact Prostate Cancer Treatment Options?

What Is a Prostate Cancer Genetic Mutation?

What Is a Prostate Cancer Biomarker?

 


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how to access the most personalized prostate cancer therapy for your individual disease and why it’s essential to insist on key testing. 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 on that link to access information to follow along during this 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. 

All right, let’s meet our guest today. Joining me is Dr. Maha Hussain. Dr. Hussain, would you please introduce yourself? 

Dr. Hussain:

Sure. Thank you, Katherine. 

It’s my pleasure to join you. And to the audience, nice to meet you all virtually. My name is Maha Hussain. I am a genitourinary medical oncologist with a focus on prostate cancer and bladder cancer. And I am a professor at Northwestern University Feinberg School of Medicine, Department of Medicine, and endowed professor there. And I also serve as the deputy director for the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 

Katherine:

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

Dr. Hussain:

My pleasure. 

Katherine:

I’d like to start by asking about developments in prostate cancer research and treatment. Experts recently gathered at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. 

So, what were the highlights from that meeting that you feel patients should know about? 

Dr. Hussain:

I think probably perhaps I can focus on two major – what I would consider major highlights, and those were the results from two randomized Phase III clinical trials. 

One of the trials is called the VISION trial. And the VISION trial was a Phase III randomized trial evaluating lutetium-PSMA-617 treatment in patients with metastatic castration-resistant prostate cancer. And the delightful thing about this study is that that study was positive. The PSMA story has been really going on for a few years now. And there’s the PSMA for purposes of scans, imaging, to assess the cancer. And the FDA just approved a PSMA PET imaging this year. 

I think it was in May when it was approved. And that would help better define if the cancer is spread or not, and it help with the decision regarding treatment. But the second part is treatment purposes, so identifying the cancer location and trying to attack it with a specific sort of targeted attack to the tumor is really important. 

And so, the FDA is currently looking at this particular agent. And I am hopeful that we will hear soon from the FDA, hopefully before the end of the year, and maybe – who knows? – maybe by summer, middle summer or end of summer. Because I do think that would be a major benchmark in there. And so, that’s one thing. 

The other clinical trial that I thought was interesting from a data perspective – and for disclosure, I am one of the investigators on this study. And this was an intergroup Southwest Oncology, or SWOG, sponsored clinical trial. So, it’s a federal study that Dr. Aggarwal presented. And this was a study that was aiming at maximizing, again, the anti-tumor therapy with the use of a drug which I call is the younger brother of abiraterone. 

So, abiraterone is a drug that is FDA-approved and has been around for several years right now for both castration-resistant prostate cancer and certainly hormone-sensitive metastatic disease. And so, TAK 700 (Orteronel) is a younger brother, I call it, of abiraterone. And one of the potential advantageous when this trial was designed was the fact that you don’t need to use prednisone. And the trial was completed. It was a national clinical trial. And what was interesting is that there is certainly what appears to be a potential benefit, but not in terms of the conclusive based on the way the study was designed.

Having said that, what I thought was remarkable is that patients who basically were only on the control arm was LHRH therapy, so this could’ve been like Lupron, Zoladex, or something like that plus bicalutamide, which is what we call combined androgen deprivation. And that was sort of like the strongest control arm we could do at the time when the trial was designed. 

Remarkably, the patients who were on that arm had a median survival of basically 70 months. That’s the median. That’s the bell-shaped curve with the number in the middle. Seventy months is probably the longest ever in any other randomized trials in this disease space, in the hormone sensitive space. So, that tells us is that men are living longer with prostate cancer, even though it’s metastatic disease; and, yes, it’s not necessarily curable, but men are living longer. And it’s a function of all of the better treatments that are supportive care and everything that was going on.  

And so, the control arm, as I mentioned, was the 70.2 months. The actual experimental arm was about 81.1 months. And again, I don’t know where things will go from this. Obviously, I’m not the sponsor not the FDA. But the point here is that men are living longer, and so wellness and health become even more so important than we ever did. And as I tell my patients, every day you’ll live longer. The odds of living longer is there because of better treatments coming on. 

So, to me – not to take too much time from the interview – to me, these were the two highlights: new, approved – I’m sorry, new treatment that I’m hoping will be FDA-approved and, obviously, the fact that men are living longer.  

Katherine:

How can patients keep up to date on the research that’s going on? 

Dr. Hussain:

I’m a bit biased, obviously. I’m a member of ASCO. 

And what I would recommend to my patients is to look at the cancer.net website. The cancer.net is a website that is an ASCO-generated website specifically for patients and families to review. It is vetted. The committees are not run just by physicians, oncologists, a multidisciplinary team, but also patient representative. So, the lingo and the presentation are lay-friendly, I call it, there. 

The other part I would say, the NCI website, and the American Cancer Society, the American Urological Association. I would say there’s a lot of stuff on the media. The difficulty is vetting what is sort of fake, what is not so accurate, or bias versus there. I also think that the NCCN has also some resources for patients. 

And one thing I always tell patients: explore, look, but make sure that you talk to your doctor about the meanings of everything because sometimes it can be not – it could be misleading, I should say, or maybe not very clear on what the implications are. 

Katherine:

Right. One thing that’s a topic on the mind of many people right now is COVID. 

Dr. Hussain:

Yeah. 

Katherine:

Is the COVID vaccination safe and effective for prostate cancer patients? 

Dr. Hussain:

The answer is yes and yes. So, I have to say, by default, I deal mostly with older men. Age brings in other comorbidities. And certainly, while I see all kinds of shades of gray in terms of the disease extent, going all the way from newly diagnosed all the way to end-stage disease, the bulk of the patients I end up seeing tend to have more systemic disease and have other issues going on. And I have to say, surprisingly, less than a handful of my patients had the infection. 

Only one required hospitalization with supportive measure, but not even needed incubation; however, he needed a lot of CPAP and other respiratory support. I’m not aware of any of my patients or my colleague’s patients who deal with prostate cancer that have died from COVID. So, I would say that’s the good news and that we have not seen a big hit in the population that I deal with. 

I also know that I would say 99.9 percent of my patients have opted to be vaccinated, and they have tolerated the vaccine just fine. There’s only one case, which I actually even saw just this week, who had been vaccinated but have a very, very severe end-stage disease with significantly compromised bone morrow, who got infected but hospitalized for a few days and is recovering. 

And so, I would say just by the pool of patients I see, my answers are yes and yes. 

Katherine:

Very good. Thank you. 

Dr. Hussain:

And I would encourage all the audience to go get vaccinated. I myself am vaccinated. And I’ve advised all my family members to be vaccinated, just to clarify that too. 

Katherine:

Good. Good to know. Dr. Hussain, we’re going to spend most of this conversation talking about advanced prostate cancer. But before we move on, would you give us a brief overview of the stages of prostate cancer? 

Dr. Hussain:

Absolutely. So, with any cancer, we count sort of like four stages. But I would say in prostate cancer the biggest thing is when the cancer is newly diagnosed, which could be confined to the prostate or locally advanced, meaning the cancer has gotten outside the capsule of the prostate but still within that pelvic region. 

There is the group of patients who have pelvic lymph nodes at time of diagnosis. And of course, that is the patients who have systemic disease, which would be technically stage four. Now, the systemic disease implies any abnormality that is found on scans that is beyond the public region. So, that could be lymph nodes in the back of the belly. That could be thoracic lymph nodes. That could be neck nodes. That could be lung lesions, of course, or bone, or liver. 

Now, the most common area where the cancer goes to is really – when we talk about metastatic disease – is the bone. And then lymph is another area where the cancer goes to. Prostate cancer that is confined to the prostate is curable in the vast majority of patients. There is a category of men who undergo surgery or radiation, and then their PSA begins to go up afterwards. 

And this is what we call biochemical relapse. And this is a situation where we know that, in all likelihood obviously, especially of the patients who have had their prostate out, that the cancer has spread. With the current imagine, a good chunk of times, we do not find anything because we’re able to pick up PSA that goes from undetectable to 0.2 to 0.3, but there’s not enough cancer to show up on the scans. We’re hoping, obviously, the better scans, the PET Axumin scan, the PSMA scans are going to help us to identify sites of metastases. 

But this is a group of men where if there is no cancer visible and the only thing we’re dealing with is PSA that’s going up, if they’ve had surgery, then there’s room for what we call salvage therapy with radiation and hormonal treatment. The case is a bit different if there’s only just the prostate – if radiation was given previously. And of course, we talked about metastatic disease. 

Katherine:

Yeah. Once someone has been diagnosed, what tests are used to help understand the aggressiveness of their disease and their overall prognosis? 

Dr. Hussain:

Well, I think there is different basic things, as in, what was the extent of the cancer? How did it look under the microscope? And what is the PSA levels? So, these are the general things. There are different sort of genomic panels that the urologist will use to kind of decipher and other things to kind of help with figuring out aggressiveness and things like that. What I would say is this, is a patient who is diagnosed and has a cancer, and at a minimum has what we consider a Gleason 7 prostate cancer – so, that’s the scoring system that is done with the original Gleason score, or the new patterns where it’s talking about intermediate risk to high risk – to me, this is a cancer that needs to be treated. 

And again, that’s all to do with if a person has other comorbidities, they have some other terminal condition that’s a separate story. But talking generically, that would be when we would recommend. And these are the patients that are generally not seen by the medical oncologist. They’re seen by the urologist, and then they can refer them to radiation oncology also for consultation. 

Katherine:

Now that we understand how test results can help inform a patient’s cancer and how it may behave. Let’s discuss how they can affect treatment options for men with advanced disease. First, let’s do a brief review of the treatment types currently available. There’s hormone therapy, right. What else? 

Dr. Hussain:

Perhaps, it’s simpler if we focus on advanced disease, specifically metastatic disease. 

So, if that’s the deal, then the backbone of treatment is hormone treatment. And it really is. We call it hormone, but technically it’s an anti-hormone. What we’re trying to do is shut down the hormonal pathway that stimulate the testes, which is the factory that makes testosterone. So, we are looking at shutting down testosterone production from the testes in order to starve the cancer. 

Now, the male hormone is produced predominantly – somewhere about 95 percent of it is made by the testes, and then there are about 5 percent-ish that comes from other sources. These are, again, male hormones like the adrenal gland and so on. And there was a while ago some research – I want to say from the MD Anderson crowd, but this is two years ago – that suggested also that the tumor may start to make sort of in-house production of male hormone to support itself. 

Now, having said that, again, testes continue to be the source of the majority of the male hormone. And so, historically, the first data that showed benefit was actually by surgically removing the testes, which is what we call orchiectomy or bilateral orchiectomy. And then medications began hitting the market and were evaluated in the late ’80s and then 1990s, beginning with Lupron – which by the way, in the ’80s, it was an injection that the patient had to give themselves every day, which is remarkable. 

But even then, there is a personal preference by patients to go and take injections as opposed to go through surgery with orchiectomy. But still, I would say for some patients it may be an option until it ought to be discussed as an option. Then what we know is this, is because of the potential other sources for the male hormone, the concept of what we call combined androgen depravation was being evaluated. 

And again, this goes back to the ’80s when the first drug was flutamide and then bicalutamide, and there are other drugs that became. And they kind of added a sprinkle, I call it, to survival. But it wasn’t dramatic, huge differences in survival. And so, generally, while we used it, everybody believed in using it. Moving forward, the drugs like abiraterone, enzalutamide, apalutamide are the three hormonal drugs that have demonstrated conclusively really an advantage in terms of prolonging life when added to the Lupron. 

So, what I tell my patients is that, when it comes to hormone treatment there is really no way around it. You can delay it. Some people are exploring for some patients who don’t have a lot of cancer, maybe a couple of areas, maybe just do targeted radiation and then leave the person alone to buy them some treatment-free time. 

And, to me, this is where the discussion that has to happen with the patient. What is the objective? Is the objective to kind of be ahead of the game and maximally treat the cancer with the hope of prolonging life? Or is the objective to delay treatment? And I would tell you that, with these types of conversation, nine out of 10 or 9.5 out of 10 men opt for moving aggressively up front with management. So, that’s that. 

Now, the one thing I should point out, one of the trials that also was a landmark trial in this disease was the study CHAARTED, which was an intergroup clinical trial at the time it was designed, led by ECOG, and the PI was Dr. Chris Sweeney. I was part of the team that worked on the design also of the study. 

And that was a trial that looked at adding docetaxel to hormone therapy, versus hormone therapy alone, to try to see if it adds something. Historically, all the chemotherapies prior to that that were added to hormone treatment for patients with newly diagnosed metastatic disease had not delivered. And docetaxel did. 

However, one thing I should point out, based on that trial – and I don’t want to go into too much details for the sake of time – the patients that seemed to be benefiting were the patients that had more aggressive, more disease in their system. And so, liver metastases, lung metastases spread in the bone at different areas, not like few isolated areas in the spine or the pelvis, but much more than that. 

And so, for the patients who have what we call high-volume prostate cancer based on scans – and I’m happy to explain what that means if it’s needed – these are the patients that I would offer either the docetaxel plus hormone treatment, which is the injection, or the injection plus the hormonal pills that I mentioned earlier. 

Katherine:

What about targeted therapy? How is that used? 

Dr. Hussain:

Okay. So, let’s begin with the molecularly targeted therapy. So, as we speak right now, for patients who have newly diagnosed metastatic disease that we call hormone sensitive, molecularly targeted therapy is not standard of care. So, I would encourage patients who may qualify for clinical trial to be involved in those. The flipside is – we can talk about it – is that molecularly targeted therapies, specifically with PARP inhibitors have pretty much entered in the space of prostate cancer with a couple of drugs that were FDA-approved. 

The other way of targeted treatment, which would be what we refer to targeted radiation, this would be a different story. This is not systemic treatment. This is a local treatment. And what is done is basically if patients do not have a lot of cancer in their body based on scans, and only certain areas, and they are starting systemic therapy, they can certainly consult with a radiation oncologist to target radiation to areas that are visible on scan. So, if somebody has a couple of, let’s say, pelvic bone lesions, maybe a lymph node, and they are already starting systemic therapy, they can consult with a radiation oncologist focal radiation. And so, that would be the general scheme. 

Katherine:

Many patients are confused about the role of genetics and biomarker testing in prostate cancer care. 

For people who haven’t heard of some of these terms before, let’s go into the definitions. So, what is genomic or biomarker testing, first of all?  

Dr. Hussain: So, I think there’s one thing. Maybe I can explain because the wording can be confusing. So, there is the genetics, and there is the genomics. The genetics would be what we inherit from our families. So, this would be present in our body. The genomics testing would be to look for what the structure of the genes of the cancer itself, cancer cells itself. Now, that doesn’t mean that this was inherited. It’s just that this is a renegade, and it evolved. And that is what is going to show up. 

The reason these two are important, both of them have implications potentially for treatment or perhaps clinical trials. And again, with the PARP inhibitors, the BRCA-like genes will have implications for treatment sort of for resistance cancers. 

With regard to the genetics, the implications are for, again, inheritance of family and potential risk for blood relatives. Now, there are panels that are FDA-approved for the purpose of genetic testing. And the requirement or the indications right now, anybody who presents with metastatic disease or an aggressive disease and diagnosis, the recommendation is to proceed with the genetic testing, certainly counseling and testing, because there are some people who prefer not to be tested. And that’s something else. 

What I tell my patients is this, even if the testing is done and it was negative for inherited genes that might put the patient family at potential higher risk, the fact that a person has prostate cancer by default puts potential, adds risks to family, to blood relatives. 

And the risks aren’t just for the males with regard to prostate cancer, but certainly breast cancer, ovarian cancer, pancreatic cancer potentially, and things of that sort. So, this is where I think a patient needs to be discussing with their doctors. And certainly, there are many centers that have genetics counselor, and so that’s where I generally refer my patients to. I counsel them myself, and then refer them also for more discussions with genetics counselor. 

Katherine:

What exactly are genetic mutations? And how do they impact a treatment path? 

Dr. Hussain:

Well, I think, again, it’s the changes that happens in specific genes that may promote the aggressiveness of a cancer. And so, the BRCA gene is one of the oldest genes that have been identified in breast cancer. And essentially, the body regulates itself. 

And when cancer cells come up and they sort of – the body no longer sustains that regulation, the genetic regulation in those cancer cells. Those cancer cells will behave the way they want to. That means that they’re going to grow faster. That means they could be resistant to treatment and things like that. And so, that’s what we check for, these alterations. And there are certain medications that would allow – and again, in prostate cancer, it’s not a lot. It’s just, as I said, right now the only things that are proven is the PARP inhibitors. This is essentially to kinda gang over the cancer cell, preventing from allowing it to repair itself so it can continue to grow. 

Katherine:

Some patients may not know if they’ve received these important tests. So, for patients that aren’t all that sure, what key questions should they be asking their physician or their specialist? 

Dr. Hussain:

So, I would say when it comes to the genetics testing, I believe a patient has to consent. 

Because again, we live in the U.S., and this is a private matter for the patient. So, this generally has to be the case. Otherwise, depending on the institution, sometimes some tests will require for the overall testing for looking for any genetic alterations, general tumor alternation. Different centers have different things. But the patient should ask and say to their doctor, “Have my cancer genes been tested? Have my genes been tested? And if they have, what are the results?” Because we generally share with the patients once it’s been done. 

The other things I should point out, some of the good things that have happened recently. Up until recently, when it comes to the tumor genomic testing, tissue was required. Nowadays, the FDA has approved blood tests that several companies now run that can actually collect blood sample and basically test it for circulating tumor cell genes there. 

Now, no testing is 100 percent perfect. But in situations like patients with prostate cancer who may not have recent tissue or adequate tissue for testing, certainly doing the blood test to verify if there is anything reflective of the genes of the cancer, and that may allow for potential actionable-type treatments. Again, up until now, this is more going to apply for potential clinical trials or resistant metastatic disease. 

Katherine:

Are there other important factors to consider, like a patient’s age, that can help them access the best treatment for their prostate cancer? 

Dr. Hussain:

Yes. And I think that age is one factor. What I say and what I tell my fellows, age is to be respected, but used to discriminate in terms of management. 

 We all age. And certainly, the body reserve is not the same. And so, that’s why I would say that has to be respected. But it doesn’t mean that we cannot treat patients. 

And I’ll tell you, it’s interesting. There are times where you have – I have a gentleman who used to run seven miles a day. He was 87 years old. This was in my days when I used to be in Ann Arbor at University of Michigan. And the gentleman came to me, and he said, “Dr. Hussain, I don’t feel good.” And I said, “Sir, why? What has happened?” “I can’t run like I did before.” And I said, “You’re not running?” “No, I am running. I’m just not able to do seven miles a day. I can do only four miles a day.” I’m like, whoa, that’s about 100% more than I do. 

Now, again, I’m bringing this as an extreme example. But for some of the oral agents, like the Olaparib trial, there were men in there literally late-’80s, early-’90s that were included in the clinical trials. Same thing goes for several of the other trials. 

I do think that functionality is important. So, if somebody comes to you so sick they are in a wheelchair, you really have to be very careful. And again, I’m just using kind of extremes. And so, you have to be careful by what you are able to do. And any time the doctor thinks the odds are going to be more harm than good, this is really where absolutely a situation where the physician needs to be careful about it, and the patient needs to understand it also. At the end of the day, it’s a shared decision. 

Katherine:

Before we close, Dr. Hussain, how do you feel about the future or prostate cancer research, and what would you like patients to know? 

Dr. Hussain:

First, let me say that I would love for the patients to know that they are a partner, a most critical partner in the process.  

That we need to continue the research and investment in research. It is research that will end up curing cancer. Wishful thinking will not do it. And patient volunteering, which I think is remarkable across all cancers. The business I’m in, the way that drug discovery and evolution often happen because patients volunteered. And without testing these new treatments and combinations, we will not be able to get better results.  

And I will tell you that, when I started my training, the median survival for patients with resistant prostate cancer was on the magnitude of about nine months. Now it is three years-plus. Now, you could argue, well, that’s not huge. But that is a huge change because, again, we’re picking up the cancers much earlier. And the patients who had, as I mentioned, metastatic disease, again, the longevity then at the time I was in training, but even afterwards, was give and take in the three years. And now we’re talking six-plus years. 

And so, there’s been tremendous progress. And really partnership with the patients and their families and supportive others is very critical, and investment in research. So, yes, advocate constantly for more investment in research. 

Katherine:

All sounds very promising, Dr. Hussain. Thank you so much for taking the time to join us today. 

Dr. Hussain:

My pleasure. And be well, all of you.  

Katherine:

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

How Do Genetic Mutations Impact Prostate Cancer Treatment Options?

How Do Genetic Mutations Impact Prostate Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

 How do genetic mutations impact prostate cancer treatment options? Dr. Himisha Beltran shares how information about genetic mutations play into treatment decisions and discusses the role of PARP inhibitor therapies and immunotherapies.

Dr. Himisha Beltran is Director of Translational Research in the Department of Medical Oncology at Dana-Farber Cancer Institute. Learn more about Dr. Beltran, here.

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Transcript:

Katherine Banwell:

Dr. Beltran, are there gene mutations that affect prostate cancer treatment choices?

Dr. Beltran:

Yeah. So, we’re still really in the infancy of precision medicine in prostate cancer, but we’ve come a very long way. The field has identified several classes of mutations that have treatment implications for men with advanced prostate cancer. One class of mutations is in a pathway we call homologous recombination DNA repair. So, what this really is, is a pathway that consists of multiple genes. BRCA2 is the most common, but there are many within this gene family. And this pathway is important in maintaining DNA repair in a cancer.

There are specific types of mutations that can affect treatment choices for advanced prostate cancer. And there are drugs that specifically target these mutations. So, testing for them in is important in the clinic. The drugs that approved today fall into two classes of medications. One is a class of medicines called PARP inhibitors. These drugs specifically are geared towards patients whose cancers harbor mutations in a pathway called homologous recombination.

So, how these mutations impact the cancer is that they work to repair the DNA of a cell. And if a cancer cell has a mutation or a loss of function of one of these genes, they can still survive because there’s another pathway that can come in and take over. If you can now come in what a drug called a PARP inhibitor, and you block that other pathway, those cells are particularly vulnerable. And they die through a process we call synthetic lethality. And so, this is really the rationale for using a PARP inhibitor specifically for patients whose cancer have an alteration in this pathway.

And I mentioned there are a number of genes that are involved. And so, typically, the way they’re tested for is looking at either the primary cancer or a metastatic biopsy or a liquid biopsy. There’s a number of tests that are available to try to look for these mutations. There is a second class of drugs that is approved for prostate cancer patients based on genetic mutations. And that is a class of drug called immunotherapy. But the drug that’s approved is pembrolizumab. The way this drug works is it’s immunotherapy, meaning that it stimulates the patient’s own immune system to fight the cancer.

And this drug does not work in every patient with prostate cancer. We know it only works in a minority of patients whose tumors have specific vulnerabilities that make them amenable to this. And there a number of ways we test for it. There is something called hypermutation where there’s a lot of mutations in the cancer, mismatch repair deficiency which can be detected by DNA sequencing as well as protein expression. And there’s something called microsatellite instability. And so, these are tests that we are also commonly doing. It’s rare in prostate cancer, less than five percent, but it important because there a class of drugs that approved that can specifically target this.

And then, beyond these two pathways that I refer to, there are a number of emerging therapies that are specifically geared towards mutations in the DNA. So, as we do sequencing, we commonly get more information than just this. There are other common mutations in prostate cancer with clinical trials really geared towards individualizing care based on those mutations, whether it be through targeted therapies or immunotherapies or other approaches. So, the field is really moving very quickly. And so, it’s now quite relevant to test to for mutations where it wasn’t the case really not that long ago.

Why Prostate Cancer Patients Should Consider Participating in a Clinical Trial

Why Prostate Cancer Patients Should Consider Participating in a Clinical Trial from Patient Empowerment Network on Vimeo.

Dr. Sumit Subudhi explains why prostate cancer patients should consider participating in clinical trials, the role they play in treatment options for prostate cancer and resources available to find trials. 

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:                   

What would you say to patients who are nervous about participating in a clinical trial?

Dr. Subudhi:                 

Yeah. This is a common question that I deal with in clinic, because we tend to have a lot of trials at MD Anderson. And the first thing, for me, is to understand why they’re nervous, because there’s different reasons why people are nervous.

Some people have heard of placebo trials, where the experimental drug that they’re hoping to get is only given to a portion of the patients and not all. And so, patients are worried what if they get on the placebo arm. And so, what I tell patients in that case is that please note that you’re going to be monitored very closely – more than usual, and so I’ll be seeing you in clinic more often. And if there’s any signs of progression, I will take you off the study. But I also always have a back-up plan. So, I tell them this is the next drug I’m going to give you if you progress, so don’t worry, I’ve got a plan for you. So, that’s one thing.

The other thing that people get concerned about are experimental drugs – just the fact that they are experimental. And I have to remind them that all these standard therapies that we have for prostate cancer were all experimental at one point. And it was the courage of the other patients that went through clinical trials that helped bring it as standard of care. And then sometimes some people have issues with travel, and those are more logistical issues. And especially now with the COVID era, we have to think about that. And so, we’re also trying to find and use networks to see if there’s other trials that are more amenable for patients so they don’t have to travel far.

Katherine:                   

How can patients find out about clinical trials that may be right for them?

Dr. Subudhi:                 

Yeah. So, one way is using clinicaltrials.gov. And that’s a website that allows you to search for specific trials either by drug name or by disease type – so, for example, prostate cancer. So, that’s one resource. And the others are cancer societies like the American Cancer Society or ASCO or Prostate Cancer Foundation. They also have links to clinical trials that are exciting. 

Prostate Cancer: How to Know If Your Treatment Plan Is Working

Prostate Cancer: How to Know If Your Treatment Plan Is Working from Patient Empowerment Network on Vimeo

How do you know if a prostate cancer treatment plan is effective? Dr. Sumit Subudhi, a Medical Oncologist, explains how a patient’s treatment response is monitored for its effectiveness.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Targeted Prostate Cancer Therapies vs. Chemotherapy: What’s the Difference?

 


Transcript:

Katherine:                   

How can you tell if treatment is working?

Dr. Subudhi:                 

So, I actually use three criteria to figure this out. One is the patient’s self, their symptoms. So, some patients’ symptoms are related to the urinary tract system, such as they may have frequent urination, or they can have pelvic pain in that area or blood in the urine or problems with ejaculation.

Other patients have pain because they have metastasis to the bone, and so the bone pain can be a symptom. And when a treatment is working, these things will actually start resolving. And so, you’ll see that these symptoms start disappearing without pain medications or other things. So, symptoms is No. 1.

No. 2 is in prostate cancer, unlike many other cancers, we actually have a serum test, or blood tests, that we can follow, which is the PSA. And usually when that’s going down, that’s reassuring.

The third is scans – radiographic scans, such as CAT scans and bone scans, help us monitor the disease. In an ideal world, all three will be going in the same direction. Meaning if the treatments working, the patient’s symptoms have improved, if they had symptoms. The PSA is going down and third, the scans show that things are improving. But the truth is we don’t live in an ideal world.

And to me, the patient’s symptoms always trumps. And I’ll give you an example. Early on in my career, I had a patient that was getting hormonal therapy, and their PSA was zero. And he started having right hip pain. He had a traditional scan – a CAT scan and bone scan – done which showed that everything was stable. And remember, the PSA was zero. And so, I told him, I looked at your history carefully, and you had a right hip repair 10 years ago. I have a feeling that that’s probably what’s causing it.

So, he went to go see his orthopedic surgeon. And he comes back, and he says, no, the orthopedic surgeon says it’s your fault. So, I did an MRI, and the patient and the surgeon were absolutely right. So, I got tricked, because I fell in love with the PSA. And ever since then, the patient’s symptoms trumps everything else. It’s my job to figure out and rule out that this is not prostate cancer. So, my point is don’t fall in love with the PSA, because even if it’s zero, that doesn’t mean that you’re in the clear.

Katherine:                   

How long do you monitor a patient before you make the decision that the current treatment not working, let’s move on to something else?

Dr. Subudhi:                 

Yeah, good question. So, for each type of treatment and for each patient, I personalize how often I will see them.

For example, if someone is having significant pain, then I’m more likely to see them more often in clinic to make sure the pain is under control, but also to monitor how their treatment is going. And that means I’ll also scan them or do radiographic scans with the CAT scan and bone scan more frequently. Now, someone that’s more asymptomatic, you’ll see the intervals are longer. So, it’s really personalized for each patient. And the type of treatment they’re receiving, as well. So, it depends if they’re getting chemotherapy versus hormonal therapy versus a PARP inhibitor. So, all these play a factor, so it’s not a one-size-fits-all.

Targeted Prostate Cancer Therapies vs. Chemotherapy: What’s the Difference?

Targeted Prostate Cancer Therapies vs. Chemotherapy: What’s the Difference? from Patient Empowerment Network on Vimeo

Targeted prostate cancer therapies and chemotherapy are both available options to treat patients with prostate cancer. Dr. Sumit Subudhi discusses the differences between these two forms of treatment, including their effectiveness and side effects.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:                   

Let’s turn to targeted therapies. How exactly do they work?

Dr. Subudhi:      

Yeah. So, this is a form of personalized medicine. So, what you’re doing is you’re looking at the patient’s cancer, either their inheritable cause of genetic causes or the somatic. And then you’re saying, oh, wait, they have a genetic defect in a DNA machine. So, let’s use the PARP inhibitor, which also targets the DNA machinery.

And these are the cancer cells that are most likely to be susceptible to PARP inhibition. And actually, the cancer cells will die from it. Whereas if a patient has a normal DNA machinery, the PARP inhibitors will actually not have any effect on the cancer. 

They’re given, actually, orally twice a day. The two drugs are rucaparib and Olaparib that have been FDA approved for this indication.

Katherine:                   

How do these newer treatments differ from traditional chemotherapy?

Dr. Subudhi:                 

So, with chemotherapies, at least in prostate cancer, they’re given intravenously every three weeks. And the goal of the chemotherapies, they are actually designed to kill any actively dividing cell in the body.

And the problem is it’s not just cancer cells that are actively dividing in our body. For example, with the chemotherapy such as docetaxel or cabazitaxel, that’s used in prostate cancer – their brand names are Taxotere and Jevtana – these chemotherapies will also affect hair loss. Why? Because hair grows really fast. And in fact, I need a haircut every three to four weeks, which my wife has been helping me with.

So, the chemotherapies are targeting all actively dividing cells, and that’s why you also get nausea vomiting, because the cells of our GI tract are also affected by that. So, chemotherapies are not personalized. They’re there to kill actively dividing cells. Luckily prostate cancer divides a lot more quickly than any other cell in our body, and that’s why they’re susceptible to chemotherapy.

Katherine:                   

And as far as the targeted therapies, Dr. Subudhi, are there side effects with those?

Dr. Subudhi:                 

Yeah, there are. One of the most predominant side effect is actually anemia. And so, that’s when the red blood cells in our body are lower than usual. And so, that’s one of the major side effects for PARP inhibitors. But in addition, you can have nausea, vomiting, and diarrhea as other side effects with the PARP inhibitors.

How to Become a Partner in Your Own Prostate Cancer Care

How to Become a Partner in Your Own Prostate Cancer Care from Patient Empowerment Network on Vimeo

Staying up-to-date about prostate cancer can help patients become partners in their own care. Dr. Sumit Subudhi explains how self-advocacy can play an essential role in helping patients become an active participant in their care decisions.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:

Dr. Subudhi, what advice do you have for patients who may be hesitant to speak up an advocate for themselves when it comes to their own care and treatment?

Dr. Subudhi:

Yeah, I’d say that it’s interesting because we all do this ourselves. And when it comes to our car – let’s say a car breaks down, or if we’re trying to buy furniture – we’ll get three, four different opinions. But for ourselves, for our own body, we don’t do that. And when you watch – we were talking earlier about Major League Baseball – and these players, when they get injured, they get the three best specialists in the world to evaluate them. And they’re seeing the best of the best.

And so, we owe it to ourselves and the patients owe it to themselves to actually get second opinions. I encourage it. I encourage my patients to get second opinions, even if I’m the first doctor they see, because I want them to feel comfortable with their decision.

And it’s important to understand that just because you’re seeing a doctor doesn’t mean that it’s a one-size-fits-all. You will get different opinions from different doctors, and you have to go with the one that makes you feel most comfortable.

Katherine:                   

We have a question from the audience, Dr. Subudhi. Amy is saying she’s the daughter of a prostate cancer patient. And she’s curious to know how she goes about getting genetic testing, and if her children should be tested, as well.

Dr. Subudhi:                 

Yeah. So, one of the things is that family history is very important in determining who should get genetically tested. So, if you’re a prostate cancer patient and you have metastatic disease, you should get genetically tested. And the reason for that is because we have a new set of drugs, the PARP inhibitors. But if you’re a family member that’s wanting to know whether you have a loved one has inheritable cancer that you may end up inheriting, that requires more understanding of the family history.

For example, did the grandfather have prostate cancer? Did the uncle have prostate cancer? And as I mentioned earlier, it’s not just prostate cancer. Is there a family member with breast cancer or ovarian cancer? These things play out in the decision-making of who should be genetically tested.

Promising Prostate Cancer Treatment and Research News

Promising Prostate Cancer Treatment and Research News from Patient Empowerment Network on Vimeo

Are there advances in prostate cancer treatment that patients should know about? Dr. Sumit Subudhi shares prostate cancer research news and discusses highlights from this year’s American Society of Clinical Oncology (ASCO) meeting.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:

As a researcher in the field doctor, Dr. Subudhi, what would you like to leave patients with? Are you hopeful?

Dr. Subudhi:

Yeah, I’m very hopeful. It’s a really interesting time, because with the technological advances and scientific advances – Traditionally, prostate cancer has always been treated just with hormonal therapies from the 1930s all the way to early 2000. Then in 2004, chemotherapy became the next thing. And then after chemotherapy, we’ve now got a dendritic cell vaccine; we’ve also got a radiopharmaceutical agent. And so, what the point is now we have a lot more different FDA-approved agents. And now, experimentally, the PARP inhibitors have now become a standard of care for those patients with mutations in the BRCA1, BRCA2, or ATM.

And then, in addition, we have many other types of technologies, such as BiTE and CAR T cells, that are coming out that are showing in early studies to be exciting. And so, I feel like that these therapies in combination may actually lead us to cure the cancer.

Katherine:                   

ASCO happened in June. Was there any news that patients should know about?

Dr. Subudhi:                 

Yeah, so the PARP inhibitors got a lot of press during ASCO, as they should, because this is a new class of drugs that is the first personalized version of medicine that we have in prostate cancer. Now, personalized medicine has been around for a long time in cancers such as breast and lung cancer. But for first time, we actually have it in prostate cancer.

Katherine:                   

Dr. Subudhi, I want to thank you so much for joining us today.

Dr. Subudhi:

Thank you for your time. I really appreciate it.

Katherine:

And thank you to all of our partners. To learn more about prostate cancer and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell.

How Can You Access Personalized Prostate Cancer Treatment?

How Can You Access Personalized Prostate Cancer Treatment? from Patient Empowerment Network on Vimeo.

How could genetic testing results affect your prostate cancer treatment plan? In this INSIST! Prostate Cancer webinar, Dr. Sumit Subudhi will discuss key prostate cancer tests, the latest targeted therapies and tools to help you advocate for a personalized treatment approach and insist on better care.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

Download Program Resource Guide

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Three Key Steps to Take Following a Prostate Cancer Diagnosis

 

 


Transcript:

Katherine:                  

Welcome to Insist Prostate Cancer, a program focused on empowering patients to insist on better care. Today we’ll discuss the latest advances in prostate cancer, including the role of genetic testing and how this may affect treatment options.

I’m Katherine Banwell, your host for today’s program. And joining me is Dr. Sumit Subudhi. Welcome, Dr. Subudhi. Would you please introduce yourself?

Dr. Subudhi:        

Hi, I’m Sumit Subudhi. I’m a medical oncologist at MD Anderson Cancer Center, and I specifically focus on prostate cancer.

Katherine:    

Excellent, thank you. Before we start, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Well, Dr. Subudhi, I’d like you to begin with a brief explanation of the stages of prostate cancer.

Dr. Subudhi:               

Yeah, that’s a great question. So, we use stages, and there’s four – Stage I, II, III, and IV. And we use it to help us determine what treatments the patients need for their prostate cancer. In general, Stage I is localized prostate cancer, and it’s localized only to the prostate. And when we do a digital rectal exam, we cannot feel or palpate the prostate.

And the treatment for Stage I prostate cancer is either active surveillance, where you’re not trying to cure the cancer, you’re just actively watching it, and you’re using a PSA imaging studies, prostate biopsies, and digital rectal exams at regular intervals to follow the patients. But other patients with Stage I prostate cancer can actually get definitive treatment for curative intent with radiation therapy or surgery. Stage 2 prostate cancer is also localized, but on physical exam, we can actually palpate or feel the prostate cancer. And this also can receive definitive treatment for the prostate to cure it, and that, also, you can use radiation therapy and surgery.

Stage III is what I consider locally advance. This is where the prostate cancer is now starting to leave the prostate. And it still can be cured by radiation and surgery, but most likely needs a multidisciplinary approach, where you might need both or maybe even in addition of a systemic therapy. Stage IV is the last stage that I’ll talk about, and it has distant metastases. And here we’re not looking for a curative approach; we’re actually looking for palliation, which means that we’re trying to treat the prostate cancer as a chronic disease.

Katherine:                  

I understand that there are many types of prostate cancer that have been identified. How can patients advocate for a precise diagnosis?

Dr. Subudhi:    

Yes, you’re absolutely right. There are many types. So, we have historically used histological classification. And when I say histological, that means when we look at the cancer under the microscope, we can look at the different structures within the prostate cancer and classify them.

And there are multiple types such as adenocarcinoma, neuroendocrine, small-cell, mucinous, etc. But more recently, with the advances in genetic and molecular testing, we now can look at the genes inside the prostate cancer, and that has also helped us better classify the cancer. Now many of these types of approaches are best done at major cancer centers, where they have experienced pathologists who actually evaluate both histologically and molecularly the cancer.

So, I recommend to my patients, or family and friends, that have been diagnosed with prostate cancer that they don’t necessarily have to go to the major cancer centers. They can have their local doctor send the tissue from the biopsy to the advanced cancer centers to get a second opinion.

Katherine:    

But this would be an initial visit to a doctor. Is that right?

Dr. Subudhi:    

Good question. So, I’m presuming that the patient is actually being seen at a local center where they have a local doctor, and so they don’t have to come, for example, to MD Anderson Cancer Center to see me. They could actually have their tissue sent to our pathologists and get it reviewed, and they can still be at home. And especially in this era of COVID, that’s important.

Katherine:      

What is the role of genetic testing in prostate cancer?

Dr. Subudhi:     

That’s a great question, because this is something that wasn’t really available when I was training and understanding prostate cancer. But over the last few years, this has actually hit the mainstream, and it’s very important. And I see it having three roles. The first role is whether or not you can receive a certain type of targeted therapy or systemic therapy known as PARP inhibitors. So, if your genetic test is positive for certain markers – that I think we’ll cover later – then it can help give you more treatment options. The second is that generate testing can give you also risk of other cancers besides prostate cancer. For example, if you have the BRCA mutation, you’re 15% to 20% more likely to get breast cancer in men.

The third is that because the genetic testing is looking for inheritable mutations in your genes, that means you can pass it along to your kids. And this could have a tremendous impact on the screening strategies your children want to use in the future.

Katherine: 

Would you mind going into that a little bit?

Dr. Subudhi:  

Yeah.

Katherine:  

For instance, my ex-husband had early prostate cancer. My 22-year-old son is worried now about also getting prostate cancer. His grandfather had prostate cancer.

Dr. Subudhi:               

Yeah, great question. So, it’s not just about prostate cancer. So, prostate cancer, genetically, is linked to other cancers, as well.

So, in your case, you’re turning by your son. But if you have daughters or any female members in the family, consideration needs to be given to breast and ovarian cancer. And for both men and women, we also have to think about melanoma and pancreatic cancer. So, it’s not just prostate cancer that we’re thinking about when you have these genetic risks. And that’s very important, because each of these different cancers can have different screening modalities.

Katherine:                  

Oh. Well, how is the testing administered then?

Dr. Subudhi:               

The testing is actually a blood test, so very simple.

Katherine:                  

Have there been any major advances in testing?

Dr. Subudhi:               

Yeah, so when we’re talking about the inheritable testing, that’s just a simple blood test. And the reason why it can be done simply through the blood is because every cell in your body has it. So, when they collect the blood, they can just take any cell from there and do genetic analysis. And if that gene is mutated or missing, it will be captured.

Now, there’s another type of testing where they test your tumor tissue itself – so, your cancer tissue – whether you got it by biopsy or surgically removed. And so, that’s a different type of testing. That’s looking for what we call somatic mutations. These are not inherited mutations. These are mutations that are specific for your prostate cancer. Again, in contrast, the inheritable mutations are in every cell in your body – not just your prostate cancer cells, but every cell in your body. And the somatic, it’s just in your prostate tissue itself.

And so, sometimes with prostate cancer, it’s difficult to get the tissue. And what’s happened more recently – and to answer your question – is that the advances have been in what we call liquid biopsies, where they are able to use your blood and get the DNA from the tumors and actually genetically test the cancers that way. And so, that’s where the future is going.

Katherine:      

Oh, that’s amazing. Are there specific tests that patients should ask their doctor for following the diagnosis?

Dr. Subudhi:   

Yeah. So, if inpatients with high risk or metastatic prostate cancer, they should definitely be considering tests to see if they have mutations in what we call the DNA damage repair pathway or homologous recombination DNA pathway. And I know they’re fancy terms. What these genes are, they’re genes that help the body repair their DNA, and DNA is very important. And so, when there’s defects in the DNA repair pathway, then mutations occur. And these mutations can actually help the cancer grow.

Now what’s happening is that what they’re looking for in these genetic tests – whether it’s the inheritable test or the somatic mutation test that’s looking just within the tumor itself – they’re looking to see if there’s any DNA damage machinery that’s defective. And if it is, then you’re more likely to benefit from PARP inhibitors, which are oral drugs that specifically target the DNA repair pathway.

Katherine:    

All right. Dr. Subudhi, what is the link between inherited mutations and prostate cancer?

Dr. Subudhi:               

Yeah, so in approximately 10% to 15% of patients with prostate cancer, they have an inheritable cause for their cancer. And so, this predisposes them to not just having prostate cancer, but potentially to other cancers, but also their family members.

Katherine:                  

Would you give us an overview of common mutations in prostate cancer?

Dr. Subudhi:               

Yeah. So, in regards to the inheritable causes, the BRCA mutations – BRCA2 and BRCA1 – are very common. In fact, BRCA2 is more common than prostate cancer than BRCA1. In addition, there’s CHEK2 and ATM which are common inheritable mutations. And the other ones are the mismatch repair genes. Again, all these play an important role in repairing DNA. So, if you’re mutated in these genes, then your ability to repair DNA has been significantly diminished, and you’re more likely to gain more mutations.

Katherine:                  

How do these mutations affect disease progression?

Dr. Subudhi:               

Yeah. So, what they can do is they can lead to mutations that make the cancer grow more. And there’s two ways to do it. You can have a mutation in what we call an oncogene, a gene that when it’s active, it’s going to just promote the cancer.

And then we have other genes called tumor suppressor genes. Their normal function is to prevent the cancer from growing. But if the tumor suppressor gene gets mutated so it’s no longer functional, then the cancer can then take off, because it’s no longer suppressed. So, those are how these genes can actually affect the prostate cancer.

Katherine:                  

What about treatment options, what’s available?

Dr. Subudhi:    

Yeah. So, if you have either an inheritable mutation in these genes or a somatic mutation, then there’s a chance that the PARP inhibitors could actually work for you. And the PARP inhibitors, they actually target cancers where there’s a defect in the DNA repair pathway.

Now, there’s one thing that I want to point out that a lot of people sort of are missing, and it’s not a subtle point. Not all inheritable mutations are made the same – or even somatic mutations. Meaning, what we’re learning is the PARP inhibitors seem to be more active with the “Braca,” or BRCA, mutations and the ATM mutations. Whereas, they’re less active with other types of DNA repair mutations. So, the point is not all mutations are made the same.

Katherine:                  

Let’s turn to targeted therapies. How exactly do they work?

Dr. Subudhi:      

Yeah. So, this is a form of personalized medicine. So, what you’re doing is you’re looking at the patient’s cancer, either their inheritable cause of genetic causes or the somatic. And then you’re saying, oh, wait, they have a genetic defect in a DNA machine. So, let’s use the PARP inhibitor, which also targets the DNA machinery.

And these are the cancer cells that are most likely to be susceptible to PARP inhibition. And actually, the cancer cells will die from it. Whereas if a patient has a normal DNA machinery, the PARP inhibitors will actually not have any effect on the cancer.

Katherine:                  

Oh, I see. Just as a follow-up, how are these targeted therapies administered?

Dr. Subudhi:               

They’re given, actually, orally twice a day. The two drugs are rucaparib and Olaparib that have been FDA approved for this indication.

Katherine:                  

How do these newer treatments differ from traditional chemotherapy?

Dr. Subudhi: 

That’s a great question. So, with chemotherapies, at least in prostate cancer, they’re given intravenously every three weeks. And the goal of the chemotherapies, they are actually designed to kill any actively dividing cell in the body.

And the problem is it’s not just cancer cells that are actively dividing in our body. For example, with the chemotherapy such as docetaxel or cabazitaxel, that’s used in prostate cancer – their brand names are Taxotere and Jevtana – these chemotherapies will also affect hair loss. Why? Because hair grows really fast. And in fact, I need a haircut every three to four weeks, which my wife has been helping me with.

So, the chemotherapies are targeting all actively dividing cells, and that’s why you also get nausea vomiting, because the cells of our GI tract are also affected by that. So, chemotherapies are not personalized. They’re there to kill actively dividing cells. Luckily prostate cancer divides a lot more quickly than any other cell in our body, and that’s why they’re susceptible to chemotherapy.

Katherine:   

And as far as the targeted therapies, Dr. Subudhi, are there side effects with those?

Dr. Subudhi:     

Yeah, there are. One of the most predominant side effect is actually anemia. And so, that’s when the red blood cells in our body are lower than usual. And so, that’s one of the major side effects for PARP inhibitors. But in addition, you can have nausea, vomiting, and diarrhea as other side effects with the PARP inhibitors.

Katherine:  

What are you excited about in prostate cancer research right now?

Dr. Subudhi:  

So, to me, it’s the combination of treatments. So, not just treating with one PARP inhibitor or just one hormonal therapy, it’s combining these approaches, and especially with immunotherapies, so that we can potentially cure what’s considered incurable cancer. To me, that’s the most exciting.

Katherine:   

What would you say to patients who are nervous about participating in a clinical trial?

Dr. Subudhi:    

Yeah. This is a common question that I deal with in clinic, because we tend to have a lot of trials at MD Anderson. And the first thing, for me, is to understand why they’re nervous, because there’s different reasons why people are nervous.

Some people have heard of placebo trials, where the experimental drug that they’re hoping to get is only given to a portion of the patients and not all. And so, patients are worried what if they get on the placebo arm. And so, what I tell patients in that case is that please note that you’re going to be monitored very closely – more than usual, and so I’ll be seeing you in clinic more often. And if there’s any signs of progression, I will take you off the study. But I also always have a back-up plan. So, I tell them this is the next drug I’m going to give you if you progress, so don’t worry, I’ve got a plan for you. So, that’s one thing.

The other thing that people get concerned about are experimental drugs – just the fact that they are experimental. And I have to remind them that all these standard therapies that we have for prostate cancer were all experimental at one point. And it was the courage of the other patients that went through clinical trials that helped bring it as standard of care. And then sometimes some people have issues with travel, and those are more logistical issues. And especially now with the COVID era, we have to think about that. And so, we’re also trying to find and use networks to see if there’s other trials that are more amenable for patients so they don’t have to travel far.

Katherine:     

How can patients find out about clinical trials that may be right for them?

Dr. Subudhi:               

Yeah. So, one way is using clinicaltrials.gov. And that’s a website that allows you to search for specific trials either by drug name or by disease type – so, for example, prostate cancer. So, that’s one resource. And the others are cancer societies like the American Cancer Society or ASCO or Prostate Cancer Foundation. They also have links to clinical trials that are exciting.  

Katherine:                  

Do you recommend having patients see a specialist?

Dr. Subudhi:               

Absolutely. I think that if you have a metastatic disease, you need to have a medical oncologist on board that can still work with your urologist, who’s more surgically trained.

Katherine:                  

Right. Well, we’ve talked about COVID a couple of times, and I’d be remiss if we didn’t touch upon it now. What should prostate cancer patients be considering at this time, especially those with advanced disease?

Dr. Subudhi:               

Yeah, so what I don’t want are people to say, oh, I can wait a little bit longer to contact my physician, whether it’s primary care or a prostate cancer doctor, because of COVID. I think it’s very important that the medical team is up to date on a patient’s symptoms and what’s going on medically, whether it’s related to prostate cancer or not. And so, that’s one of the messages we’ve been trying to pass on to our patients.

And with every single patient, we try our best to see if we can provide medical care as well as expertise without having physically see them through telehealth, whether it’s through video or whether it’s just through a simple phone call. So, we’re trying to look at that with each individual patient. Now, sometimes when there’s treatment decisions that have to be made – especially like do we start chemotherapy? – it’s harder to do that over the phone. But sometimes what I’ll do for my patients that are in areas where COVID is really worrisome, I’ll work with the local medical oncologist and talk to them and basically see if we can develop a plan together so that the patient can be served best.

Katherine:                  

Is there a time when telemedicine is more appropriate than others?

Dr. Subudhi:               

I think that has to be a case-by-case basis. And that’s how we do it in clinic.

Every week, a week before hand, I go through my entire clinic list – I go through each patient’s case – and I say, okay, this is a patient that would be better served with telemedicine, this is a case that I really need to see the patient to get a better sense of what to do next.

Katherine:                  

If a patient has to go into clinic, what safety measures are in place for them?

Dr. Subudhi:               

Yeah, so I can only speak for our hospital and how we’re doing it. But there’s actually like a thermal scan where when you walk in the building, they actually measure your temperature without you even knowing it. But they delete it, so it’s not something that’s kept. And this is still kept private, so you don’t have to worry about public disclosure of your temperature. And so, they’re monitoring both the staff and the patients – their temperatures. The staff themselves have to go through screening questions that they have to answer every time, and they’re actually handed a mask that’s required to be used at all times.

As far as patients go, they are also getting their temperature measured. But in addition, they are asking questions about their exposures, whether it’s family members that are asymptomatic, or not symptomatic. And in addition, the new patients will get a COVID test done prior to seeing the medical team. And for the follow-up patients, they’re not required to get a COVID test unless there’s concerns of symptoms.

Katherine:                  

Unless they’ve been exposed to somebody?

Dr. Subudhi:               

Correct, that’s right. Thanks for pointing that out. In addition, all patients are asked to wear their masks at all times, especially if they’re going to be within 6 feet of a healthcare provider or a patient or anyone else. And so, these are the measures that we’re taking to keep our patients safe.

Katherine:                  

Oh, good. Dr. Subudhi, what advice do you have for patients who may be hesitant to speak up an advocate for themselves when it comes to their own care and treatment?

Dr. Subudhi:               

Yeah, I’d say that it’s interesting because we all do this ourselves. And when it comes to our car – let’s say a car breaks down, or if we’re trying to buy furniture – we’ll get three, four different opinions. But for ourselves, for our own body, we don’t do that. And when you watch – we were talking earlier about Major League Baseball – and these players, when they get injured, they get the three best specialists in the world to evaluate them. And they’re seeing the best of the best.

And so, we owe it to ourselves and the patients owe it to themselves to actually get second opinions. I encourage it. I encourage my patients to get second opinions, even if I’m the first doctor they see, because I want them to feel comfortable with their decision.

And it’s important to understand that just because you’re seeing a doctor doesn’t mean that it’s a one-size-fits-all. You will get different opinions from different doctors, and you have to go with the one that makes you feel most comfortable.

Katherine:    

We have a question from the audience, Dr. Subudhi. Amy is saying she’s the daughter of a prostate cancer patient. And she’s curious to know how she goes about getting genetic testing, and if her children should be tested, as well.

Dr. Subudhi:               

Yeah. So, one of the things is that family history is very important in determining who should get genetically tested. So, if you’re a prostate cancer patient and you have metastatic disease, you should get genetically tested. And the reason for that is because we have a new set of drugs, the PARP inhibitors. But if you’re a family member that’s wanting to know whether you have a loved one has inheritable cancer that you may end up inheriting, that requires more understanding of the family history.

For example, did the grandfather have prostate cancer? Did the uncle have prostate cancer? And as I mentioned earlier, it’s not just prostate cancer. Is there a family member with breast cancer or ovarian cancer? These things play out in the decision-making of who should be genetically tested.

Katherine:                  

Absolutely. As a researcher in the field doctor, Dr. Subudhi, what would you like to leave patients with? Are you hopeful?

Dr. Subudhi:               

Yeah, I’m very hopeful. It’s a really interesting time, because with the technological advances and scientific advances – Traditionally, prostate cancer has always been treated just with hormonal therapies from the 1930s all the way to early 2000. Then in 2004, chemotherapy became the next thing. And then after chemotherapy, we’ve now got a dendritic cell vaccine; we’ve also got a radiopharmaceutical agent. And so, what the point is now we have a lot more different FDA-approved agents. And now, experimentally, the PARP inhibitors have now become a standard of care for those patients with mutations in the BRCA1, BRCA2, or ATM.

And then, in addition, we have many other types of technologies, such as BiTE and CAR T cells, that are coming out that are showing in early studies to be exciting. And so, I feel like that these therapies in combination may actually lead us to cure the cancer.

Katherine:                  

ASCO happened in June. Was there any news that patients should know about?

Dr. Subudhi:   

Yeah, so the PARP inhibitors got a lot of press during ASCO, as they should, because this is a new class of drugs that is the first personalized version of medicine that we have in prostate cancer. Now, personalized medicine has been around for a long time in cancers such as breast and lung cancer. But for first time, we actually have it in prostate cancer.

Katherine:

Dr. Subudhi, I want to thank you so much for joining us today.

Dr. Subudhi:

Thank you for your time. I really appreciate it.

Katherine:

And thank you to all of our partners. To learn more about prostate cancer and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell.