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Genomics + Prostate Cancer Care

Dr. David J. VanderWeele is an Assistant Clinical Investigator in the Laboratory of Genitourinary Cancer Pathogenesis at the National Cancer Institute. He is particularly interested in investigating the progression of clinically significant prostate cancer.

Prostatepedia spoke with him about how genomics impacts patient care.

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What is genomics, and how does it differ from genetics?

Dr. VanderWeele: Typically if you’re talking about genetics, you’re talking about an individual gene or a small set of genes. When you refer to genomics, you’re referring to all the genes or a very large set of genes. Genomics usually refers to the genes–the DNA sequence. But sometimes genomics is also used to refer to when those genes get expressed (as RNA), or to other changes to the DNA that don’t change the DNA sequence (also called epigenetics).

What do and don’t we know about why some men develop curable or indolent prostate cancers while some develop widely lethal diseases?

Dr. VanderWeele: A lot of effort has been put into trying to learn more about the genes you inherit from your parents and how that influences the likelihood that you’re diagnosed with cancer. Most of that effort has been unable to identify which alterations in your genes make it more likely that you will get an aggressive versus an indolent cancer.

As many of your readers probably know, many people get indolent prostate cancers. In fact, many autopsy studies have looked at patients who have died of other reasons and have never been diagnosed with prostate cancer. Once men reach their 70s or 80s, it looks like more than half of men develop prostate cancer. Of course, those are relatively slow-growing cancers.

The most information that we have now is that men who come from families with breast and ovarian cancer syndrome appear to be more likely to get cancer and more likely to get aggressive cancer. These involve BRCA1, BRCA2, and other DNA repair genes in a similar pathway. Though there aren’t FDA-approved therapies yet, there are trials suggesting that these patients are also more likely to respond to certain therapies approved for breast and ovarian cancer.

This is a pretty small subset of all the men with prostate cancer, but the percentages increase with any kind of measurement of aggressiveness. If you look at people with localized cancer, that percentage increases if you have high-grade cancer versus low-grade cancer. The percentage increases if you compare people with advanced castrate-resistant prostate cancer to those with localized cancer.

If you look at the length of time between a man’s diagnosis and when he dies, that rate increases significantly the shorter that time is. That is just looking at three of these genes, BRCA1, BRCA2, and ATM. If you look at a broader number of these DNA repair related genes, it looks like ten to twelve percent of all patients with castrate-resistant prostate cancer harbor a mutation that they inherited from their parents. It seems likely that for most of those patients, that inherited gene contributed to their prostate cancer.

That has led to some debate about how often we should test for mutations in these genes. Is that a high enough number that we should test everyone with castrate-resistant prostate cancer? Should we still rely on family history to provide guidance for which people should be tested?

Is it really expensive to test those men? Why wouldn’t you just go ahead and test?

Dr. VanderWeele: Depending on how you do it, testing costs have come down quite a bit.

But when you’re testing for genes that could potentially be passed on to your offspring, or that siblings or other family members may have inherited, there are implications for your other family members, not just for you.

Some members of your family may definitely want to know that information and think that more information is better. Others may feel that if they find out that they harbor that gene mutation, they will just feel like they’re waiting for the other shoe to drop. It’s not information that they’d want to know.

Generally, we advise people to get counseling to help them think through some of these issues before getting tested for genes they’ve inherited from their parents.

Do we know why some men respond to certain drugs and therapies and others don’t?

Dr. VanderWeele: There’s a lot of interest in that. There has been some progress made in terms of identifying the biomarkers that might suggest which patients are more likely to respond to which types of therapies. At this point, however, most patients still get treated with most therapies.

There are some genetic biomarker-driven therapies that look like they’re on the horizon. Patients with mutations in BRCA2, ATM, and related genes are more likely to respond to a type of therapy called PARP inhibitors, which are currently approved for patients with ovarian or breast cancer, but not yet for prostate cancer.

There was a single Phase II study that showed that patients who had loss of a specific tumor-suppressor gene called

PTEN are more likely to respond to a certain type of targeted therapy. There are larger ongoing trials to demonstrate that these are indeed predictive biomarkers for response to these therapies.

There are companies like FoundationOne and GenomeDX that look at the molecular features of a man’s cancer. Are those tests useful? What do they tell a patient?

Dr. VanderWeele: The FoundationOne test looks for mutations, deletions, or amplifications of specific genes that are relevant for a wide array of cancers. There are a lot of companies offering this type of sequencing.

Many hospitals offer their own version of it. A FoundationOne type of test can tell you if you have a mutation in BRCA2 or ATM. They should also be able to tell you if you have a deletion in PTEN. When they detect a mutation is present, however, generally they are not looking to determine if you inherited those changes from your parents versus the mutation being present only in the tumor cells.

These genetic tests are more popular in other types of cancers, because for prostate cancer there aren’t yet any FDA-approved therapies that would be given based on the results of these tests. These tests will become more popular as we make progress in demonstrating the benefit of these specific therapies and in our ability to predict which patients are most likely to respond.

If a patient reading this gets one of those tests, is it likely that his doctor is going to know what to do with the results? Will the results actually impact his treatment?

Dr. VanderWeele: There are probably a small number of patients who will have a result that will directly impact their therapy. At this point, the way that it would impact therapy is that it might suggest that they should find a clinical trial testing a specific type of drug.

I see.

Dr. VanderWeele: There are also other commercially available prostate specific genetic tests, like the one performed by GenomeDX, that are mostly aimed at men with localized prostate cancer who are trying to decide how aggressive their therapy should be. Typically, this means whether they should pursue active surveillance or get surgery or radiation.

Sometimes these tests are also used to determine if a patient should get radiation after undergoing a prostatectomy or if he should just continue to follow PSA numbers. The prostate specific gene expression tests are RNA-based tests, which are a little different.

They measure the levels of expression of a few specific genes. Tests like FoundationOne look for mutations, amplifications, or deletions of genes—which means they are DNA-based tests.

Tests like Decipher are more widely used now, right?

Dr. VanderWeele: Yes. They’re probably used mostly by urologists. My sense is that how often urologists order those tests and how heavily they rely on them versus other ways to predict the risk level of the prostate cancer varies quite a bit from urology practice to urology practice.

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Dr. David VanderWeele: Why Prostate Cancer?

Dr. David J. VanderWeele is an Assistant Clinical Investigator in the Laboratory of Genitourinary Cancer Pathogenesis at the National Cancer Institute. He is particularly interested in investigating the progression of clinically significant prostate cancer.

Prostatepedia spoke with him about why he became a doctor.

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Why did you become a doctor?

Dr. VanderWeele: Physicians come to the job through a number of ways. For me, it was both an interest in biology in general and in cancer biology specifically. I really enjoyed learning in undergraduate school, and later on in training, how cancer represents a normal biological process gone awry.

Of course, many people also have a family member who helped inspire their choice, either directly or subconsciously. My mother had breast cancer; I’m sure that was part of my internal motivation and interest in oncology.

How did you end up specializing in prostate cancer?

Dr. VanderWeele: I was interested in genitourinary oncology—prostate cancer, bladder cancer, kidney cancer, and testicular cancer—because there is a wide range in the natural history of those diseases and how we treat them. I became especially interested in prostate cancer in part because some prostate cancers are very aggressive and others are more indolent. The first step of managing prostate cancer is assessing the risk of the disease and not just treating all cancers the same way.

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Differences Between Prostate Cancer Genomic Tests

Eric A. Klein, MD, is an international leader in the biology and management of prostate cancer. Dr. Klein serves as Chairman of the Glickman Urological & Kidney Institute at the Cleveland Clinic.

Prostatepedia spoke with him about the differences between the various genomic tests available to prostate cancer patients.

Dr. Eric Klein: These tests measure the expression of genes in prostate cancer. That’s what they’re designed to do. They predict the likelihood of your having higher-grade cancer or cancer that penetrates the rind around the prostate (called extraprostatic extension), or cancer in the lymph nodes or seminal vesicles. These tests predict that better than biopsy or plain old Gleason grading. This gives us a leg up in deciding who is a good candidate for surveillance.

If your biopsy only shows Gleason 6, but you actually have higher-grade cancer in the prostate, or you have some cancer that’s through the rind or in the seminal vesicles, you’re not a good candidate for surveillance. We know that from decades of doing radical prostatectomies. These patients are at highest risk for progression and that’s what these tests measure.

They also tell us whether a pure Gleason 6 cancer is one of the 5-10% that has molecular features of high-grade cancer.

These are biopsy-based tests. For example, if a patient has a biopsy that shows Gleason 6 cancer and otherwise favorable features, such as a PSA below 10, and a PSA density below 0.15, we wonder whether he’s a candidate for surveillance. We always do a confirmatory test after a first biopsy. Decipher can also be used after the prostate has been removed to help decide on the need for additional treatment.

A genomic test like this is appropriate in some patients. An MRI of the prostate is appropriate in others. Sometimes it’s appropriate to get both. We don’t have enough experience to know which is the best test for which scenario, although I have some ideas about that. Then, once we confirm that the patient has a low-grade cancer that lacks molecular features of high-grade cancer, we feel confident in putting him on surveillance.

The results can do two things. They can confirm that the patient is a candidate for surveillance. Sometimes they can convince a reluctant patient that surveillance is the right thing. We don’t want to over-treat people who have low-grade cancers that aren’t going to kill them because the side effects of treatment are worse than the likelihood of his dying of cancer. Sometimes, the results can convince a physician that surveillance is the right thing. If you look at the criteria for putting people on surveillance, it’s mostly patients who have just a minimal amount of cancer–low-grade cancer, a Gleason 6 on a biopsy.

We published a study in the Journal of Urology recently that showed that even among patients with high-volume

Gleason 6 cancer in multiple cores— four or five remove cores—many have no molecular features of high-grade cancer. In the past, they haven’t traditionally been considered good candidates for surveillance, but based on the biology of their tumor, they are good candidates for surveillance.

You may have someone who has a couple of cores of low-grade cancer, maybe a PI-RADS 4 lesion on MRI.

You’re not sure if they’re a good candidate for surveillance or not. If a genomic test confirms the absence of molecular features of high-grade cancer, you can put the patient on surveillance. That is the kind of information that genomic tests provide. They have their nuances.

Oncotype and Decipher are good for patients with very low, low, and favorable intermediate-risk disease. Prolaris is best validated for patients who have intermediate risk disease. It doesn’t have good discriminatory value for low-grade cancers. Generally, they all measure gene expression and they’re all are used in the same way.

These tests help determine whether or not someone is a candidate for surveillance. At the moment, we don’t use these tests based on biopsy to determine which treatment to give a patient, but that’s coming. Post-prostatectomy, Decipher can help tell us that.

There are challenges to active surveillance. Say we put someone on surveillance and he starts out with 1 core of Gleason 6 cancer. A year later, he is re-biopsed and has 3 cores of Gleason 6 cancer. We don’t know whether that’s true biologic progression that requires treatment, if all that Gleason 6 cancer was there in the beginning and was just not sampled by biopsy, or if the patient grew some new Gleason 6 cancer that doesn’t have any biologic potential.

This isn’t established yet, but I believe we can use these tests for what I call serial biologic monitoring, meaning you biopsy patients a year or three apart. These tests, for the very first time, allow us to measure true changes in biology as opposed to just changes in what we see on biopsy, which may underestimate what’s going on in the prostate. This is a new paradigm.

Another common scenario is a man who has a low-grade cancer on initial biopsy (1 core, Gleason 6) and a year later has a little bit of Gleason 3+4 with 5% pattern 4 and 95% pattern 3. In the past, that would always trigger treatment. But it’s my belief, based on what we’ve learned from these tests, that this is probably not correct. Many of those men can still stay on surveillance.

Join us to read the rest of Dr. Klein’s thoughts on genomic tests for prostate cancer.

 


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Dr. Eric Klein: Why Medicine?

Eric A. Klein, MD, is an international leader in the biology and management of prostate cancer. Dr. Klein serves as Chairman of the Glickman Urological & Kidney Institute at the Cleveland Clinic.

Prostatepedia spoke with him about why he became a doctor.

Why did you become a doctor?

Dr. Klein: I don’t really know. I never remember wanting to do anything else.

Even when you were a little kid?

Dr. Klein: When I was in first grade, I missed a month of school because I had what they thought was rheumatic fever. My pediatrician came to see me a couple times a week. That doesn’t happen so much now.

No. It doesn’t.

Dr. Klein: I suspect that’s had some influence because my parents really respected him. But I can’t articulate it for you. I never wanted to do anything else. It was not an intellectual decision. It’s just what I wanted to do. I was born wanting to be a doctor.

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The Metastatic Prostate Cancer Project

Dr. Eliezer Van Allen, Assistant Professor of Medicine at Harvard Medical School, a clinician at Dana-Farber/Partners Cancer Care, and an Associate Member at the Broad Institute of MIT and Harvard, focuses on computational cancer genomics, using new technology in precision medicine, and resistance to targeted prostate cancer therapies.

Prostatepedia spoke with him about the Metastatic Prostate Cancer Project, a nationwide genomic research study for men with advanced or metastatic prostate cancer.

What is the Metastatic Prostate Cancer Project?

Dr. Van Allen: The Metastatic Prostate Cancer Project is a patient-driven research initiative whereby we researchers partner directly with patients to dramatically expand the scope of our understanding prostate cancer genetics. We try to fill in all of the missing gaps that are currently a challenge in our field. Hopefully, we’ll learn what drives advanced prostate cancer, how to treat it more effectively, come up with new drugs, and understand the differences between more indolent cancers and those that progress in the metastatic setting. Essentially, I want to answer the questions I had during my initial clinical observations way back when.

You say you want to partner directly with the patients. How does that disrupt the normal clinical trial process? Normally, patients would access trials through their doctors?

Dr. Van Allen: Exactly. That’s what I’ve done during my postdoctoral training and in my junior faculty stage. That’s what we all do: we devise the research project, write a bunch of protocols and consent forms, and get them approved in our hospitals. Then we rely on the doctors and research teams to approach patients. They consent their patients to the studies that are already defined and set in stone. We use that to research. That’s obviously been a driving force for many modern discoveries. It’s a remarkable thing.

And that’s how we have to lay the first genetic maps of prostate cancer and cancers in general. This project flips genomics on its head. We’ve been working with prostate cancer patients to build a project with, by, and for men with advanced prostate cancer, their families, caregivers, and loved ones in order to resonate with patients. We are creating a mechanism such that patients can consent without leaving their home and participate without necessarily living near an academic medical center. This helps expand the scope of what we were able to learn in new ways.

A couple of years ago, while trying to define the genetic maps of local and advanced prostate cancer, we launched the first of these patient-driven projects at the Broad Institute in metastatic breast cancer. Using social media, patient outreach, advocacy partners, and patients themselves describing what it means to participate in these projects, that study enrolled over 4,000 women and men with metastatic breast cancer. Given that we’re thrilled when the average study to define the genetic maps of prostate cancer enrolls 100 patients over the course of years, if not decades, that number in such short time is remarkable. As we developed that project, I immediately thought of prostate cancer.

Rather than doing a top-down research project whereby we start with an idea in a researcher’s head, we go through the hospital and the doctors, and eventually, the patients, we’re starting with the patients. They’re talking directly to the researchers and building up. That is the ethos of this project.

This is not a traditional, academic project whereby we generate all the data, sit on it in our own little groups while we try to make sense of it, and eventually make it available to the larger community. Rather, as soon as we have a nominal amount of data, we make it immediately available to any researcher around the world who wants to use it. We’re trying to create a resource that anyone could use. The first 100 patients with genetic and clinical data have been made available for researchers pre-competitively. We don’t wait and publish these results in an academic journal or any other medium first.

Publishing in a traditional academic journal can restrict access for patients. If they want to read to read the results, they have to pay $30 to download the article.

Dr. Van Allen: Exactly.

If someone reading this wants to participate, what do they do?

Dr. Van Allen: If you have advanced prostate cancer, simply go to mpcproject.org. There, the homepage describes what’s involved. When you click the “count me in” button, it sends you on what we hope is a very quick journey through a few basic questions. Then, it asks for your permission or consent to participate in this project. There are a few more simple questions after that.

Soon after you register, you’ll receive a box that contains a saliva kit that the patient will spit in and return to get their inherited DNA information. Additionally, there’s a liquid biopsy kit, which is a vial that you bring to your doctor’s appointment to collect a liquid biopsy of your tumor. Then you return the sample to us.

When we receive those materials, we perform genetic profiling and access the medical record data. We de-identify everything to make sure it’s private, so nothing is exposed. We build a cohort and learn as we go.

Each step of the process has been vetted, scrutinized, criticized, and modified based on patient feedback such that we hope it resonates with this group. Part of this is actually iterating as we go. This is a research project. We’re not a clinical lab, so at the moment at least, we do not return results to individuals. But we do regularly engage with patients to share aggregate results of anything we learn in real time.

Patients won’t have access to the results of their tests?

Dr. Van Allen: Right. Unfortunately, we can’t provide individualized results, at the moment at least, because it’s beyond the scope of this project. It’s something we’re very interested in trying to explore. It creates many additional complexities. There is a holy patient/doctor relationship that we want to respect. That being said, often men will ask what’s in it for them and ask why would I want to do this?

We try to share aggregate results as regularly as possible. Patients can take those aggregate results, or any sort of interesting findings, to their doctor to consider if it’s relevant to them. Also, it’s a beautiful thing to see how patients themselves get when it comes to helping others: This is for the brothers, the sons, the patients that come after me, and I want to contribute. I want to help solve this puzzle, even if I may not see it in my lifetime. That altruistic aspect is genuinely great.

They do get to participate.

Dr. Van Allen: Yes. They’re just surprised that folks like myself, or anyone in the research world, is even talking to them. But patients are the most powerful people in this world. They have the power to really make these kinds of change

I think most people would want to participate if it’s easy to do. Are you providing detailed information about the kinds of tests you’re running so that if patients wanted to repeat them with their own doctor they could?

Dr. Van Allen: We’re doing whole exome sequencing, which looks at all the coding region of the genome on the tumor and the inherited DNA.

We are also piloting sending in liquid biopsies. One emerging technology that’s arrived over the last couple of years is the ability to detect circulating DNA that has shed from the tumor into the blood. That is an important advance for this project because most men with metastatic prostate cancer will not have had a biopsy of their tumor at the time of metastatic disease. They may have had a prostate biopsy years, if not decades, before but that tumor from way back when isn’t an accurate snapshot of what the tumor is like in the metastatic setting. Detecting a tumor in relative real time using blood is something we’re pretty excited to explore as part of this project.

For the men we sequence, we do our best effort to track down their tumor block. We go through every precaution to ensure that we don’t exhaust the tumor biopsy and that clinical care comes first. If there’s ever a need for it down the road, that’s the number one priority. We’re exploring how to use these liquid biopsies to help us in this project.

Do you handle the liquid biopsies?

Dr. Van Allen: Yes, it’s the Broad Institute.

Can anyone participate? Can non-Americans participate?

Dr. Van Allen: At the moment, we are approved so that anyone from the United States and Canada can participate. Anyone in other parts of the world can complete the survey and provide some of the patient-reported data, but we don’t currently have permission to do the subsequent genomic profiling for them. In our soft launch, we’ve scanned through self-reported information from almost 200 patients. That has already initiated some ideas for research projects we never would have imagined.

This patient-reported data is quite valuable. Anyone who, at the moment, may not be eligible by virtue of not qualifying from a regulatory perspective for our institutional review board can still contribute to this project in a meaningful way.

A fair number of people travel for medical procedures. If someone travels to the United States for radiation, for example, could they have the samples collected at a United States institution and therefore participate in that way?

Dr. Van Allen: For now, the study can only collect samples and medical records from residents of the United States and Canada. We are actively investigating methods for including international patients.

Is there a fee to participate, or is this free for men?

Dr. Van Allen: Free.

Is there anything else you think men should know about the project?

Dr. Van Allen: We’ve been concerned about patient interest and openness. In our first project for breast cancer, the social media footprint was quite high. The social media chatter is noticeable and folks feel pretty comfortable expressing their thoughts, feelings, and opinions about their disease. Even though incidents of disease is roughly the same in the United States for breast and prostate cancer, the social media footprint for prostate cancer is the complete opposite.

As we geared up for our soft launch, we were curious to see if we’d end up with the same number of participants, even if we weren’t seeing any social media chatter. People don’t talk about this disease. Indeed, on the first version of the saliva kit that we mail out to the patients, metastatic prostate cancer project was printed on the box. Men asked us to take that off the box. We didn’t understand why. One guy explained: “I don’t want the mailman to know I have prostate cancer.”

It’s that kind of challenge we’d like to help overcome. We want to make men feel more comfortable talking about this disease amongst friends, families, and coworkers. We hope this project can be the mechanism to help men open up about it. It’s encouraging that in the first ten days we’ve accrued an almost identical number of patients as we did with the breast cancer soft launch a couple of years ago. Nobody talks about prostate cancer on Twitter and Facebook, at least in open settings. We’re very curious to learn how patients become comfortable talking about this disease and about this project.

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The Genomic Revolution Comes To Prostate Cancer

Dr. Oliver Sartor, the Laborde Professor of Cancer Research in the Medicine and Urology Departments of the Tulane School of Medicine, is one of the leading researchers in advanced prostate cancer today. He is also the editor-in-chief of Clinical Genitourinary Cancer and the author of more than 300 scientific papers.

Dr. Sartor puts this month’s conversations about prostate cancer genomics into context for us.

“We can divide genomics into two different categories. The first category is germline genomics, which is the DNA with which you’re born. It’s clear that about 12% of people with advanced prostate cancer will have alterations in their inherited DNA, in particular in genes involved with DNA repair. Most common of these alterations are BRCA2. There are a variety of others that are somewhat prevalent, including ATM, CHEK2, and BRCA1. There are others that are more rare.

The implications of these germline mutations are significant for the patient: in certain configurations they may predispose a cancer to be sensitive to certain therapies, such as PARP inhibitors or platinum-based chemotherapy or (rarely) immunotherapy. There is more complexity, but knowing the germline mutation helps the informed clinician make decisions. In my practice, we test all patients with advanced prostate cancer for these germline mutations. (A National Comprehensive Cancer Network guideline suggests the same approach.)

These germline mutations represent the DNA with which you’re born. That DNA is going to have repercussions if also mutated in your family members. Men who have some of these DNA repair mutations have an increased risk of prostate cancer. In addition, there is a small increased risk of pancreatic cancer and male breast cancer for those with some of the germline mutations. Around 30% of men with BRCA2 will be diagnosed with prostate cancer in their lifetime, but that cancer is more likely to be aggressive if diagnosed. With regards to females, it’s particularly important. Females with DNA repair defects are more likely to have breast and ovarian cancer. Female with DNA repair mutations, in particular BRCA1/

BRCA2, ought to consider having their breasts or ovaries removed at an appropriate time. Prophylactic surgery has been demonstrated to be potentially life-saving for those individuals. The risk of breast cancer may be as high as 70% and the risk of ovarian cancer may be as high as 40%.

Thus, for these germline mutations there are implications for treatment and implications for the patient’s family.

We should be doing prostate cancer screening earlier in men with these DNA repair defects for prostate cancer; we should be doing biopsies at a PSA of 3 or higher, and perhaps even lower, for younger men known to be at risk. Starting screening at age 45 has been suggested by some. In addition to germline genomics, we need to also talk about somatic genomics. Data indicates that about 60% of individuals who have a DNA repair germline mutation are likely to have another second genetic mutation occur within their tumor. In addition, many of the tumors can acquire an alteration in their tumor DNA even when the germline is normal.

Taken together, about 20 to 25% of men may have DNA repair mutations in their tumor’s DNA. That makes them particularly sensitive to certain therapies such as the PARP inhibitors, as I mentioned earlier, or platinum chemotherapy. When you have two DNA repair mutations in the same cell, the likelihood of response to these agents appears fairly high.

There are also other DNA defects of considerable interest, such as alterations of the mismatch repair genes MSH-2 and MSH-6. When these alterations do occur, there is a potentially increased probability of responding to immunotherapy such as the new PD-1 inhibitors.

Overall, the guiding light today in genetics in my practice is to look at both the germline DNA and the tumor DNA. I choose to look at the tumor DNA circulating free DNA (cfDNA) tests, in particular the Guardant Health assay. The ability of other assays to corroborate the Guardant Health findings is not yet clear. There is clear data to indicate that different assays give different results, but nevertheless, I think in the early exploratory phase we’re in now, it’s important to begin to test patients in order to better understand their genomics and hopefully guide us towards better therapies. This will happen part of the time but certainly not all of the time.

There is more to the story of prostate cancer genetics. We’ve looked at androgen receptor mutations that can have implications for a response to Androgen Receptor directed therapy, such as Xtandi (enzalutamide), Zytiga (abiraterone), and Erleada (apalutamide). We’re dissecting a number of permutations that occur. It’s a complex scenario, because very few men have only one mutation. Most have multiple mutations. And in most cases, these mutations are not targetable with current therapies. This is very important for people to know.

Everybody thinks if they get a genomics test that means they’ve got a treatment. It’s not the case. Many times we get the genomics results and find that there are no known treatments we can use for that man’s particular alteration. That said, there is a subset of men who will have informative genomics while many more people will have non-informative genomics.

There is a final issue I’d like to discuss. There is currently a bit of a debate amongst physicians over the utility of PARP inhibitors such as Lynparza (olaparib) as compared to platinum chemotherapy. But it is noteworthy that platinum-based chemotherapies are inexpensive compared to PARP inhibitors. This does not require a clinical trial. (Most men will access PARP inhibitors through a clinical trial, although sometimes insurance companies are willing to try.)

As it turns out, neither the platinum-based chemotherapies nor the PARP inhibitors will be effective forever, so we do need strategies to manage patients after PARP inhibitors or platinum-based chemotherapies fail. Currently, that space is unexplored. We have to gather much more data before we can make conclusions about those with underlying DNA repair defects who have failed platinum-based chemotherapy or PARP inhibitors.

This is an area of active and important investigation that represents a conundrum for many patients today. I’ve got a patient right now going through this. We’re debating what to do next. I’ve tried to be as honest as I can when I say, “I don’t know what to do, but we’ve got to try something.”

We are in the middle of a revolution, but the parts and pieces are not yet clear. For some, understanding tumor genetics at the current level is helpful. For others, it is perplexing and expensive.

Join us to read this month’s conversations about prostate cancer genomics.

(Already a member? You can read all conversations in your copy of April’s Prostatepedia.)


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Anxiety, Depression + Prostate Cancer

Mr. Chuck Strand is the CEO of Us TOO International Prostate Cancer Education and Support Network. He discusses the anxiety and depression often associated with prostate cancer.

A cancer diagnosis of any type triggers a wide range of initial reactions and emotions. While in some instances it might provide a sense of resolution, a more typical response may include sadness, loss, fear, guilt, stigmatization, embarrassment, anger, or disappointment.

Many aspects of living with a prostate cancer diagnosis can be sources of anxiety and depression— everything from anticipating the next PSA (prostate-specific antigen) blood test results to dealing with the post-treatment impact of common side effects like incontinence and erectile dysfunction (ED).

Unfortunately, men and their partners are not always fully informed about the likely side effects when selecting a treatment. In addition to managing the anxiety resulting from ED and/ or incontinence, an unexpected decrease in a man’s sexual virility can lead to a sense of betrayal or reduced trust in his medical provider or in the medical community in general. Recognizing and learning to cope with anxiety and depression can be critically important for effectively managing life with prostate cancer.

In a recent collaborative survey conducted by Us TOO International and CancerCare, 94 percent of men who were diagnosed with prostate cancer indicated that experiencing anxiety and/or depression is to be expected. Anxiety and depression can interfere with a person’s day-today activities, responsibilities, and relationships and can impact not only the person with cancer, but also the caregiver. Helping family members manage their distress may have a beneficial effect on the distress level of the person with cancer.

The stress and anxiety associated with a prostate cancer diagnosis can be significant enough to influence a man on active surveillance to opt for treatment earlier than necessary, resulting in what is often referred to as over-treatment.

Treatment decisions must address whatever aspect of disease management is a priority for each man, after he has sufficient information on all treatment options, possible or probable side effects, and management of side effects.

One man’s priority could be to do everything he can to minimize the possibility that prostate cancer will metastasize, while another man’s priority could be to do everything possible to maintain and maximize his quality of life. It is important for a man to recognize that once diagnosed with prostate cancer, the disease will unfortunately be a perpetual issue of concern and a potential source of anxiety due to ongoing monitoring of PSA test results at a minimum, regardless of the course of action he takes. While active surveillance can be emotionally exhausting, over-treatment can result in decreased quality of life with ED, incontinence, and the potential emotional and psychological impact of having second thoughts about his treatment choice.

Symptoms of Anxiety and Depression

Anxiety and depression not only affect the quality of a man’s life, but can also keep the body’s immune system from functioning at its full capacity. Additionally, it can have a negative impact on adherence to treatment regimens. Therefore, it’s important to recognize these conditions and attempt to address them accordingly.

Anxiety is a feeling of nervousness, fear, apprehension, and worrying—typically about an imminent event or something with an uncertain outcome. Symptoms include: feelings of fatigue or weakness, sweating (for no reason), chest pains, headaches, gastrointestinal problems, or inability to rest.

Depression is a feeling of severe despondency and dejection. Symptoms include: sleeping more or less (as compared with regular sleeping habits), loss of interest in daily activities, an unusual increase or decrease in energy, changes in appetite (eating either more or less as compared with regular eating habits), increased irritability or impatience, or difficulty concentrating.

Action Items to Help

Take action rather than passively accepting anxiety and depression as a given. Begin by acknowledging the very real relationship between anxiety, depression, and prostate cancer. Take stock of your own emotions. Talk to your doctor about your concerns. Make sure your diet is heart-healthy/prostate-healthy. Exercise even if you do not feel like it. Especially if you do not feel like it! Exercise releases endorphins and neurotransmitters that promote relaxation and eliminate excess cortisol, a hormone released during stress and associated with anxiety. Get mindful and try to incorporate yoga, meditation, acupuncture, or other holistic practices into your life. These lift the body, mind, and spirit. Try to keep a positive attitude when possible, but understand that ups and downs are normal and expected during prostate cancer treatment.

If appropriate, your doctor might be able to provide a referral to a counselor who can help. Some common techniques to effectively manage anxiety include talk therapy (especially Cognitive Behavioral Therapy [CBT]) and antianxiety medications. Depression can be managed though lifestyle changes to establish more connections and support, psychotherapy (including Cognitive Behavioral Therapy), pharmacological treatment and, in advanced situations, Electroconvulsive Therapy (ECT).

Reach Out!

If you are dealing with prostate cancer and experiencing anxiety and/or depression, know that you’re not alone. Educational resources and support services are available to help cope with anxiety and/or depression.

Many men with prostate cancer and their wives/partners have dealt with anxiety and depression. It can be helpful to attend an Us TOO prostate cancer support group to share experiences and gather information and strength from those who have successfully managed these challenges.

To find an Us TOO prostate cancer support group near you, visit www.ustoo.org/Support-Group-Near-You, call 800-808-7866, or email ustoo@ustoo.org.

To join a prostate cancer support group via telephone, visit www.ancan.org/support-calls.

For individual counseling on anxiety or depression by telephone and online group counseling, contact CancerCare at 800-813-4673 or www.cancercare.org.