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Conversations With Prostate Cancer Experts


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Dr. John Gore: Why Medicine?

Dr. John Gore is a clinician, surgeon, researcher, and educator specializing in urologic oncology and general urology at the University of Washington.

Prostatepedia spoke with him about how Decipher changes the way doctors treat men with prostate cancer.

Why did you become a doctor?

Dr. John Gore: My initial vision for my life was that I was going to be a lawyer. Then I found that I really enjoyed my experiences while interning at the hospital. That brought about an application to medical school. I think being a doctor offers a chance to have a daily meaningful impact, which is a unique part of the job.

How did you end up working in urology?

Dr. Gore: Urology is a specialty that very few people enter medical school thinking that they want to do. In part, most people are like I was and don’t even know about the specialty. I don’t have any doctors in my family. The only doctor I knew was my own pediatrician. I just assumed I was going to be a pediatrician.

But I really enjoyed surgery. I enjoyed being in the operating room. I just really enjoy the generic construct that someone has a problem and I have the tools to fix it.

Urology is an interesting hybrid. Most surgeries have a homolog in internal medicine. For example, there’s cardiothoracic surgery and cardiology. There’s colorectal surgery and gastroenterology. We don’t really have that in urology. We do a lot of chronic disease management. We do a lot of long-term follow-up of our own patients. It is, in many ways, a hybrid of internal medicine and surgery, which is really cool.

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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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Dr. Felix Feng: Why I Became A Doctor

Dr. Felix Feng is a physician-scientist at University of California, San Francisco (UCSF) keenly interested in improving outcomes for patients with prostate cancer. His research centers on discovering prognostic/predictive biomarkers in prostate cancer and developing rational approaches to targeted treatment for therapy-resistant prostate cancer. He also sees patients through his prostate cancer clinic at UCSF.

Prostatepedia spoke with him about why he became a doctor who cares for men with prostate cancer.

Why did you become a doctor?

Dr. Felix Feng: I became a doctor because my family has a strong history of cancer. Unfortunately, I learned the repercussions of cancer at an early age. All four of my grandparents passed away from some form of cancer. My father has successfully overcome three different cancers. Just last year, my sister, unfortunately, passed away in her 40s from cancer.

Before ever becoming a doctor, I was part of many patients’ families. I saw it strongly from the patient side and decided that if I was going to commit my life to studying something, it was going to be cancer.

So then your journey is really personal.

Dr. Feng: Very personal.

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Genetic Testing + Counseling

Ms. Merel Nissenberg is the President of the National Alliance of State Prostate Cancer Coalitions, a nation-wide organization comprised of state prostate cancer coalitions dedicated to saving men’s lives and enhancing the quality of life of prostate cancer patients and their families through awareness, education, and the development of a public policy network.

She talks to Prostatepedia about guidelines for genetic testing in men with prostate cancer.

Much has been written or suggested about the genetic component of some prostate cancers. For example, a family history of prostate cancer can increase a man’s risk of such a diagnosis. There have also been articles about the genetic component of certain breast cancers: BRCA1 and BRCA2 have historically been strongly implicated in the familial pathway for that diagnosis. What is more recent is the now more-firmly established connection between certain mutations like BRCA1 and BRCA2 and prostate cancer. However, guidelines for genetic testing in men with prostate cancer have been limited.

Recently, the Journal of Clinical Oncology published a special article entitled “Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017” following the Prostate Cancer Consensus Conference held in Philadelphia on March 3-4, 2017. Members of the panel strongly agreed that men should engage in shared or informed decision-making on the issue of genetic testing.

Panel members emphasized the strength of the inherited predisposition of prostate cancer, noting higher risks with BRCA1, BRCA2, and HOXB13 genes. The panel noted that prostate cancer patients with BRCA2 mutations have poor prostate cancer-specific outcomes. We now consider the link between prostate cancer and DNA mismatch repair (MMR) gene mutations to be stronger than we suspected, adding a specific opportunity for treatment. In fact, up to 12% of men with metastatic prostate cancer have inherited genetic mutations, mostly with BRCA1, BRCA2, and ATM. And targeted agents for these specific mutations confer better outcomes for these patients.

The panel concluded that: “Identifying genetic mutations of inherited prostate cancer… has implications for cancer risk assessment for men and their families, for precision treatment of metastatic disease, and is being incorporated into guidelines for individualizing prostate cancer screening strategies specifically for male BRCA1 and BRCA2 mutation carriers.”

Unfortunately there are no generally accepted standard guidelines for genetic counseling and genetic testing in prostate cancer, or standards on how to fully interpret results of current panels with multiple gene testing. The information discovered through genetic testing not only informs treatment for the prostate cancer patient himself, but is also an aid to other members of his family, including women who may have a genetic disposition for developing breast cancer. As for the patient, not only does the information potentially help guide prostate cancer treatment, but it also makes both him and his clinician aware of the potential for additional cancers.

The results of the Philadelphia Prostate Cancer Consensus Conference can be read in detail in the Journal of Clinical Oncology 36, no. 4 (February 2018), 414-424. Their considerations included the following:

  • which men should undergo genetic testing for prostate cancer;
  • which genes should be tested based upon clinical or family scenarios;
  • how the testing results should be used to inform screening for prostate cancer; and
  • how results should be used to inform treatment of early stage (localized), advanced stage (high-risk), and metastatic prostate cancer. Genetic testing done thoroughly and properly can help guide screening and treatment decisions.

The National Alliance of State Prostate Cancer Coalitions strongly endorses the use of genetic testing and genetic counseling for prostate cancer, and urges clinicians to read, consider, and follow the scientifically sound suggestions of the 2017 Philadelphia Prostate Cancer Consensus Statement on the Role of Inherited Prostate Cancer Risk. NASPCC will be presenting a Webinar on Genetic Testing and Genetic Counseling in Prostate Cancer on May 9, 2018. It is supported by Myriad Genetics. (Visit https://naspcc.org/index.php/may-9-2018-naspccwebinar to register.)


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Patients Help Shape Prostate Cancer Genomics Study

Joel Nowak is a prostate cancer patient and well-known prostate cancer activist.

Prostatepedia spoke with him about his involvement with the Metastatic Prostate Cancer Project.

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What is the Metastatic Prostate Cancer Project?

Mr. Nowak: This is a joint project between the Broad Institute and the Dana-Farber Cancer Institute. But what is really more important to me is the researchers who are involved: Dr. Corrie Painter and Dr. Eliezer Van Allen are really committed to what they’re doing. They’ve modeled this project off of a metastatic breast cancer project that they also started.

One of the researchers is a cancer survivor, so they understand what it means to have cancer. Their understanding motivates what they’re doing. They’re carrying it forward; they’re not just doing it because they have a grant.

How did you come onboard with the Metastatic Prostate Cancer Project?

Mr. Nowak: My friend Jack Whelan, who I’d worked with at the American Association of Cancer Research Scientist↔Survivor Program, had a very rare blood cancer. Then one day he surprised me by saying he’d been diagnosed with prostate cancer. I thought he was joking at first.

Unfortunately, his cancer progressed really quickly, probably related to all the treatments he had for his blood cancer. The project staff brought me, Jack, and Jan Manarite in to work on the project. They asked me to look at their materials and give a patient’s perspective. They wanted to know if I found value in the project

They asked me to give them specific feedback and suggestions for improvement. Jack, Jan, and I have also brought in two others. Dr. Van Allen’s team has taken all of our suggestions and made the changes.

They also asked us to spread the word, let people know about it, reach out within the prostate cancer community, and help recruit.

What is it about the project that makes it patient-friendly?

Mr. Nowak: The project is patient friendly because once someone consents and says, “Count me in,” the project team does all the work. They send out a package, which we advocates helped redesign, and you just contribute your spit. Then you bring your sample back to the post office or FedEx; it’s all prepaid. Spit it and ship it. That’s the effort.

We also send out blood vials that are also prepaid. Theoretically, you can walk into a lab and they’ll draw your blood for free. Or you can bring the vials to your next doctor’s appointment. You don’t even have to make a special appointment; just ask them to draw an extra tube.

It’s easy.

Mr. Nowak: Yes. It’s easy, and it’s all prepackaged. Either you or the phlebotomist can just put it into the prepaid package and send it off. You don’t have to do much.

Part of the consenting process is the release of the medical records. The project does the sequencing of the blood and saliva, and if applicable, we ask for tissue. There’s not a lot of tissue in prostate cancer, generally, so that was one of the issues I brought up. I wanted to ensure that no one’s tissue is used up and withheld from them for the purposes of this research, because you never know when we’ll need your own tissue for treatment decisions. We advocates said this was a big issue, so the project will only use a small piece and return it. You need to get it back: you just never know when you’ll need it yourself.

You need to look out for yourself.

Mr. Nowak: Yes. It’s appropriate to be selfish in this particular situation. The only thing you have to do as a patient is read the consent, discuss it with the appropriate people at the project, sign the paperwork, spit, and bleed. That’s all we have to do. Everything else is handled by the project. You don’t even know it’s happening; it’s all behind the scenes.

This is a research project, not a clinical trial, but even with clinical trials everything gets de-identified. That means that your personal information is safe, but you also get no follow-up information. As a patient advocate, I asked what they could do to give some feedback to patients. They were very open to having this conversation, but they are sensitive about overpromising anything. We don’t want to mislead anyone.

If we start seeing trends in the data, we will give some feedback. We can’t tell individuals that they have gene mutations or not, for example, because their sample was de-identified. But if, hypothetically, we see samples from 300 people with a combination of at least three gene mutations and that 285 people with a particular mutational sequence respond to Xtandi (enzalutamide) but not to Zytiga (abiraterone), then we will give feedback.

But this is exciting. When we start seeing trends or possible trends, the project will release information to people who participate. There will be aggregate data feedback. We’ll be able to publish relationships. It doesn’t of course stop me as a patient from going to my doctor and getting sequenced. Probably all of us should be sequenced anyway.

The patient can follow up as he chooses…

Mr. Nowak: Exactly. Then they could say, “I’ve been sequenced, and I have this mutation.” That is just an additional talking point with your doctor from the aggregate data. I’m excited about that. That’s going to give some people another thing to consider when deciding between treatments.

Why should men participate? Did you participate?

Mr. Nowak: I did. Jack and I fought over who would be Patient 1. I had respect for Jack, so I told him he could be Patient 0, and I’d be Patient 1. Technically, I’m Patient 2. Men should participate for a number of reasons. First of all, we have to think about the next generation. My prostate cancer is genetically linked. My father had it. His brother died from it, and his only child, who’s older than I, who had been treated. My grandfather had prostate and breast cancers, and my great-grandfather died of prostate problems. Many of us have or are going to have kids, so we should make it a little better for them if we can.

I spend a lot of time working with people and helping them figure out how to have a conversation with their doctor about treatment. Anything that can give us more information and more points of conversation is important. Aggregate data might help us have better conversations that may help make better decisions going forward.

This is one of those rare research projects where I could possibly benefit directly. As I start going through treatment protocols and so forth, I have no idea where they may find something that works better for me. It’s just going to guide my decision-making. Maybe it’ll extend my life because I made a better decision thanks to the project.

We also need to understand cancer more generally in terms of genetics and its microenvironments. We need to understand cancer not only as separate diseases. Prostate cancer only describes the organ from which the cancer originates. It doesn’t really describe my disease or another’s. We need to drill down and understand the type of prostate cancer that one has and how it relates to cancer generally. That is going to guide us in making better decisions.

This type of research is invaluable. There are no risks. There is nothing invasive. The more we understand, the better future research will be, whether for specific treatments or a better understanding of biomarkers, which we have a terrible dearth of knowledge about. To me, it’s a no-brainer for us who are going to benefit at no cost.

I hope men sign up.

Mr. Nowak: Yes. That’s our goal. Now that we have IRB (Internal Review Board) approval, our next step is to get men signed up.

To participate visit https://mpcproject.org/home

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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.

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Join A Prostate Cancer Imaging Clinical Trial

Dr. Peter Choyke, Director of the Molecular Imaging Program at the National Institutes of Health’s National Cancer Institute, is keenly interested in translating molecular imaging methods like MRI and PET into practice.

Prostatepedia spoke with him about his clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer.

Why did you become a doctor?

Dr. Peter Choyke: I was always interested in science. I came from a family of scientists. It just seemed that medical problems were the kind of problems that I needed to do work on. A lot of the problems in physics and chemistry had been solved, but in biology and medicine we really needed a lot more effort. I wanted to devote my life to that.

Can you explain the thinking behind your clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer?

Dr. Choyke: Prostate cancer imaging has been very limited. We’ve only had access to CT and bone scans, both of which had limited sensitivity for picking up prostate cancer. In the beginning of the 2000s, a number of new PET agents—or Positronemission tomography labeled agents—emerged. We started looking at them as they became available. They showed better and better sensitivity and specificity.

About three or four years ago, we accessed a first generation PSMA-targeted PET agent named F-18 DCFBC in collaboration with the person who invented this whole field, Dr. Martin Pomper at Johns Hopkins University.

We formed a collaboration and scanned 135 patients in an earlier protocol. We showed that even though this was a first generation PSMA agent, it was really promising and had much better sensitivity and specificity for prostate cancer than any other agent we had ever looked at.

Then Dr. Pomper, who is partly an imaging specialist and partly a chemist, further developed the compound into F-18 DCFPYL. This is the agent we’re now using in this trial.

F-18 DCFPYL has probably 10 times better sensitivity than the first-generation agent because of the higher affinity of the agent for PSMA and because of lower background. We started using that in the end of the summer of 2017 in a trial looking at high-risk primary cancer and recurrent disease.

If a man enrolls in this trial, what can he expect to happen from beginning to end?

Dr. Choyke: First of all, it’s important to talk about who qualifies for the trial. We have two arms.

In one arm, we’ll have men with high risk cancers, meaning they’re at high risk for metastatic disease or spread outside the prostate. Such men would come to our center and get the scan. They’d also get an MRI of their prostate, because we always correlate the findings of the DCFPyL scan with MRI to anatomically locate where the uptake is occurring. The anatomy is very complex in the low pelvis.

With the MRI in hand, the patient would get an injection of a small amount of radioactivity in the form of this F-18 DCFPyL. About an hour later, they go onto the scanner and simply lie flat for about 20 to 30 minutes until the entire body is scanned from head to toe. Then we’ll report the findings back to his physician.

Part of the reason why this is a research study is that we try very hard to correlate the findings that we see with biopsy specimens. This is still a research agent. We don’t know for sure that the areas of uptake are actually cancer. We can only confirm that with biopsy. We insist that patients undergo biopsy of PSMA-positive lesions as seen on the scan.

We say insist, though of course it may not be medically safe for some people to undergo a biopsy. It may not be feasible. There are exceptions. It’s not an absolute rule. We certainly want to get as much histologic correlation as possible. Otherwise, we could end up in a situation where we think we’re seeing disease, but we are in fact not. That would be very misleading and could possibly cause more harm than good. It’s very important at this stage of development to get as much information as possible.

In the second arm of this trial, we are scanning patients who have already undergone radical prostatectomy or radiation therapy and who now have a rising PSA, which indicates recurrent disease. We would do the scan in the same way as in the first arm with correlation of the MRI. Again, we’re trying to get as much histologic confirmation as possible.

Join us to read the rest of Dr. Choyke’s comments about his clinical trial.

 

 


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ZERO’s Jamie Bearse On Cancer Recurrence

Mr. Jamie Bearse is the CEO of ZERO — The End of Prostate Cancer (www.zerocancer.org). ZERO is a United States-based nonprofit with a mission to end prostate cancer.

He talks to Prostatepedia about dealing with recurrence.

Finishing your prostate cancer treatment is cause for celebration and relief. Life is best lived in the moment as we all only have today. However, stress about side effects and thoughts of recurrence creep in. It’s critical not to live in an anxious world of what if, but it’s important to know that up to 40 percent of men will experience a recurrence after completing treatment. For those who do experience recurrence— whether it is biochemical or metastatic disease—we’d like to share some tips for coping with the journey ahead. Talk to your doctor about every aspect of your new diagnosis, including your treatment options.

It’s important to understand whether you are experiencing biochemical recurrence or if your cancer has become metastatic and what your treatment options are. At your appointment, take detailed notes, or bring someone with you to do so. Afterward, do your own research about what you discussed with your doctor, and if you still feel unsure, seek a second opinion. Much like when you were first diagnosed, it’s important to understand all options available to you based on your specific disease and circumstances.

Consider joining a support group.

Support groups offer the chance to share feelings and fears with others who understand, as well as to exchange practical information and helpful suggestions. Connecting with other men whose cancer journey is similar to yours can allow you to explore options and seek advice from someone who has been there before.

Try to lean on your loved ones.

Your loved ones want to help you through this newest obstacle – try not to be afraid to open up and talk about how you’re feeling. If you don’t feel comfortable talking to someone, write down your thoughts in a journal. Talking and thinking about your concerns as you work through your options can help you feel less afraid or anxious and more in control.

Utilize all resources available to you.

If you don’t feel comfortable talking to a loved one or a support group, or if you feel you need additional support, consider calling ZERO360 at 1-844-244-1309 Toll-Free, a free one on- one patient support service that can help you find qualified counselors and emotional support resources. The fear of recurrence is normal and reasonable for all cancer survivors. Although you cannot control whether your cancer recurs, you can control how you move into this next phase of your prostate cancer journey. ZERO also offers a new, peer-to-peer MENtor program, which can match you with a patient or survivor who has experienced a similar diagnosis or treatment pathway for one-on one support. In addition, if you’re experiencing recurrence and are looking for additional resources to help, visit http://www.zerocancer.org/ get-support/zero360.

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3 or Fewer Prostate Cancer Mets

Dr. Piet Ost is a radiation oncologist at Ghent University in Belgium. His work focuses on post-surgery radiation therapy and metastasis-directed therapy for oligometastatic prostate cancer, or a cancer recurrence with three or fewer metastases.

Prostatepedia spoke with him about treating men with so few metastases after treatment.

Can you define oligometastatic prostate cancer?

Dr. Ost: First of all, if your doctor talks about oligometastatic disease, I think it’s very important to ask them what they mean by that? When we look through literature, there are several definitions used.

Some people use oligometastatic while others use oligorecurrence, synchronous metastases, or low volume metastases. Many of these probably mean the same, but there is no uniform definition.

In 1995, Hellman and Weichselbaum first defined oligometastases as metastases limited in number and location. These tumors have not developed the full capacity for metastatic growth. It could be an issue with the metastases—or the seed—or it could be an issue with the soil—the environment in which the metastases started to grow. That’s the biological definition.

This is not very useful as a clinician. What is limited? Is that a certain number? If you look through literature, many clinicians define it as up to three metastatic lesions with no more than two different organs involved. That is probably the most used definition, but there are alternatives. Some say that it’s only one metastasis while others say it’s as many as five or even 10 in case of brain metastases. Some say there has to be a certain amount of time between primary diagnosis and the occurrence of metastasis.

There’s a lot of confusion throughout the literature. If you read an article, you have to look at their definition. When doctors talk to each other, and when patients talk to each other, they all use the word oligometastatic, but it might be that they’re talking about a different disease.

Is there any sort of restriction on where those metastases are located—for example, in only the pelvic area?

Dr. Ost: At this time, I don’t think so. It’s a biological phenotype. We care less where the metastasis occurs. For example, we have had patients with unique lung mets at the time of recurrence where we remove those lung mets, and then these patients remain disease-free for many months or even years.

Normally, when you have a patient with lung mets, those are visceral mets, and their prognosis is supposed to be very poor no matter what. There appears to be a subset of patients with a limited number of metastases, even visceral metastases, who still benefit from removing or irradiating the metastases. We have several of those cases documented already. It’s not about the location. It’s something about the biology, and that is the big problem at this time.

Currently, when we propose a certain oligometastatic or metastasis directed therapy to a patient, we don’t know if the metastases we see and treat are the only ones there, or if three months after we remove or eradiate them, there will be 20 new metastases. We don’t know that at the start. This shows us that imaging is still far from perfect and sometimes we only see the tip of the iceberg.

When we look at the distribution or pattern of metastases in recurrent prostate cancer with Choline PET/CT and PSMA PET/CT imaging, we see that, after receiving prior prostate cancer treatment, the majority of patients relapse first in the lymph nodes.

That is mainly in the pelvic lymph nodes. If we look at all the patients that we screen for now, 70% have nodal recurrences, 25% have bone metastases, and 5% have visceral mets. If we look at all of those recurrences, two thirds of those relapses are what we call oligometastatic, meaning up to three metastatic spots. We don’t believe that there is a true limitation on the organs. How it evolves is actually a fingerprint of the disease.

When you start, you don’t know whether it’s a true oligomet. We cannot predict at this time how the disease will evolve.

How do you normally treat oligomets? With radiation or surgery? How do you decide which is most appropriate?

Dr. Ost: We still counsel our patients on the standard options. For patients with upfront metastatic disease, the landscape has changed dramatically where we now introduce Androgen Deprivation Therapy (ADT) plus Taxotere (docetaxel) or ADT plus Zytiga (abiraterone) as a standard of care.

We still do not know if these options are helpful in treating the primary tumor and its mets with metastatic-directed therapy. In situations with upfront oligometastatic disease, we counsel our patients that the standard of care is systemic drugs while the addition of any metastatic-directed therapy is one big question mark. We do not advise it outside clinical trial.

The situation is a bit different in the recurrent setting. In the recurrent setting, there’s a gray zone. For example, the older data said that starting ADT for a PSA relapse following primary therapies—just starting ADT—is not advised; it’s better to wait and see and do a delayed ADT at the time of symptomatic progression.

Now with the very sensitive imaging, we see mets earlier at PSA relapse. What should we do with these? Do we still say the standard of care is wait and see, ADT, or something else? Because new imaging created this gray zone, all of a sudden we saw a boom in these oligometastatic patients, so we decided to do a clinical trial in this setting.

In our paper published in The Journal of Clinical Oncology (JCO), we randomized our patients to wait and see. One group had surveillance while starting ADT, and the other group had surgery or radiotherapy to the mets followed by surveillance. In that study, we found that surgery or radiotherapy is better at postponing further progression to polymetastatic disease rather than just observing patients.

We have an alternative now in counseling patients: metastaticdirected therapy with either surgery or radiotherapy. We know that it’s very safe, because we did not see any grade 2 or higher toxicity, which is a positive thing to tell men with prostate cancer. We can offer you something without a whole lot of toxicity. We still have to tell you this was a Phase II trial. The endpoint was time to progression.

I’m still not sure that giving metastatic-directed therapy will change your disease in the long run, that it will make you live any longer compared with immediate ADT or surveillance. It’s still too early to tell. We try to counsel our patients with these different options.

Join us to read the rest of Dr. Ost’s comments. (Subscribers can read the conversation in their March issue of Prostatepedia.)