Conversations With Prostate Cancer Experts

Leave a comment

How Has Imaging Impacted Treatment?

Shore_001Dr. Neal Shore comments on this month’s discussion of the ways imaging has impacted prostate cancer treatment.

Imaging is important for newly diagnosed prostate cancer patients who may or may not have localized disease, and it’s especially important for advanced prostate cancer patients, whether they continue to be androgen sensitive or have developed some level of androgen resistance. For earlier stages of disease, there has been a lot of interest regarding multiparametric MRI. Nonetheless, the efficacy of multiparametric MRI is limited by the expertise of the interpreting radiologist. The fusion technology software championed by several of the academic centers has been rolled out without consistency within the community. For some practices, it was adopted due to marketplace competition and the device developers’ promotions. Companies that develop multiparametric fusion technology have not made a significant contribution to the advancement of urologic and radiologic educational needs. That said, some groups incorporated dedicated specialists within their practice to train for high-quality multiparametric fusion-based biopsies. Purchasing the newest promising technology without ensuring a framework to optimize clinical results will lead to poor implementation. In the United States, MRI is still mostly recommended for patients who have had a negative prostate biopsy, but due to age, PSA kinetics, or rectal examination, there is still a concern of possible malignant disease that was missed on the first biopsy. MRI is most uniformly accepted for additional information when evaluating patients for the need for a second biopsy. MRI will no doubt have an ongoing role in the active surveillance population. MRI will no doubt have an eventual role in decision making for possible first biopsies.


There has been a lot of very good, evidence-based literature coming from European countries that suggests that whole-body MRI, with the right software protocol, is exceptionally helpful in evaluating metastatic disease. Unfortunately, in the United States, this protocol takes 45 to 60 minutes to accomplish, and unfortunately, translates to a challenging economic utility model for the MRI efficiency from an administrator perspective. There are many interesting and promising blood-, tissue, and urine-based markers, genomic assays, and additional imaging techniques, which require ongoing trials to determine how best to use them for the most efficient value-based care model. No single test—MRI or any other blood-, tissue-, or urine-based marker—is perfect. Eventually, we will hopefully develop a cost-effective algorithm that combines a panel of all the different biomarkers. MRI is part of that discussion, but we don’t have that sorted out currently. There have been multiple PET scan technologies developed in the last several years that have been assessed for improved potential sensitivity and specificity, and ultimately, to improve the accuracy of the data that shows cancer spread and its location. MRI and Axumin PET scanshave been approved for advanced prostate cancer patients. There have been other PET scans such as FDG, C-11 Acetate, C-11 Choline, sodium fluoride, which have not received widespread reimbursement approvals nor widespread accessibility. There is also no consensus recommendation for these technologies.


Advances In Imaging

In October, we’re discussing advances in imaging that could dramatically improve how we treat prostate cancer. (Issue to be released to subscribers on Wednesday October 4.) In our Guest Commentary, Dr. Neal Shore does an excellent job summarizing these advances from a urological perspective, expanding on the interviews by Drs. Matthew Cooperberg and Raoul Concepcion. Dr. Michael Zelefsky discusses the impact these new imaging approaches, especially MRI, have in prostate cancer treatment planning.

Several common themes emerge. One is that the American healthcare system renders the best imaging technologies so expensive that rapid implementation at the community level is limited. The situation in Europe is markedly different; costs are 70-80% lower. As a result, Europe is leading both the development of better imaging technologies and the delivery of these technologies at a community level.

Another common theme is that advanced training and experience are required to use these imaging technologies well. Dr. Cooperberg does an excellent job of outlining this problem in prostate multiparameter MRI. The message for you is just because a nearby medical facility has purchased state-of-the-art imaging equipment does not mean they know how to use that equipment well. For now, travel to centers with a documented track record in using a new imaging technology.

Perhaps the most important point is that before a new imaging technology becomes standard treatment, extensive clinical trials need to validate the technique. How do you know when an imaging technique has passed such scrutiny? One landmark is whether or not the imaging technology has been FDA approved. For example, the C-11 Choline and Axumin imaging scans are FDA approved and covered by Medicare to detect metastatic prostate cancer. The Gallium-68 PSMA PET/CT scan is very promising, but not yet FDA approved.

In several of this month’s conversations, we mention the role of imaging in the management of oligometastatic disease. In oligometastatic disease treatment, we use radiation or surgery to eliminate metastases, potentially delaying cancer’s progression for a clinically useful time. By now, it is clear that there are patients who benefit from this treatment.

What is not clear is how effective we are at identifying who those patients are. This will only be resolved by well-designed randomized clinical trials. Fortunately, such trials are in progress and additional trials planned.

Charles E. Myers, Jr., MD


Not a member? Join us to read this month’s conversations.



Leave a comment

A New Prostate Cancer Vaccine?

Dr. Charles G. Drake of New York-Presbyterian/ Columbia University Medical Center spoke with Prostatepedia about new prostate cancer vaccines under investigation.

DRAKE charlesNot a member? Join us to read the entire conversation.

Dr. Charles Drake: Hopefully before the end of the year, a trial called PROSPECT will read out. (Though it’s hard to tell nowadays when trials are going to read out because we already have a reasonable number of options: six FDA-approved drugs for men with metastatic castration-resistant disease.) PROSPECT is an international randomized Phase III trial of about 1,200 men that looks at Prostvac, an off-the-shelf PSA-targeted vaccine. The trial’s primary endpoint is overall survival.

Unlike the Provenge (sipuleucel-T) trials, which were sometimes a little complicated to interpret because we had crossover, patients on PROSPECT didn’t crossover. That means that patients on the placebo arm who progressed were not eligible for Prostvac, instead, they went on to standard treatments. The lack of crossover means we expect a fairly clean set of survival data to come out from this large PROSPECT trial. There are a lot of folks in the prostate cancer community looking forward to seeing whether or not PROSPECT will have a survival benefit.

So then we’d have two vaccines for prostate cancer?

Dr. Drake: Provenge (sipuleucel-T) is an active drug with clear utility. The challenge with Provenge (sipuleucel-T) is that patients need to undergo leukapheresis to prepare this personalized vaccine. Prostvac is more like the vaccinia vaccine that was used for smallpox. It will be a bit easier to distribute widely.

Is inconvenience the only factor limiting Provenge (sipuleucel-T) use?

Dr. Drake: The prostate cancer field is like all other fields in that we tend to be trendy at times. When Provenge (sipuleucel-T) was first approved, there was a ton of enthusiasm about it and lots of people were using it. In fact, there was a bit of controversy over whether or not we could make enough of it.

With all the new drugs coming out, Provenge (sipuleucel-T) is probably used less than it once was. But this is something that has been FDA approved and has a clear survival benefit.

Join us to read the entire conversation.

Leave a comment

Targeted Prostate Cancer Screening

Jeffrey_SwensenDr. Jeffrey Swensen is the Associate Director of Molecular Genetics at Caris Life Sciences in Phoenix, Arizona.

Prostatepedia spoke with him recently about prostate cancer screening for men with BRCA2 mutations. (See Prostatepedia March 2017 for a discussion with Dr. Swensen about molecular profiling for prostate cancer.)

Not a member? Join us.

Should a man with a BRCA2 inherited mutation be screened earlier for prostate cancer?

Dr. Swensen: Carrying a pathogenic BRCA2 mutation increases the risk for prostate cancer, and that cancer is more likely to be aggressive and earlier onset. There are recommendations that suggest male BRCA2 carriers should be screened more aggressively for prostate cancer. Male BRCA2 and, to a lesser extent, BRCA1 mutation carriers are also at increased risk for other cancers, including male breast cancer and pancreatic cancer. Screening male BRCA2 mutation carriers for breast

cancer is generally recommended; screening for pancreatic cancer is generally not unless there is a family history of that cancer.

Would it make sense to offer prostate cancer screening to male children of a prostate cancer patient earlier?

Dr. Swensen: No. A man with a BRCA2 mutation tends to get prostate cancer at an earlier age than the standard person in the population. But it’s generally not really early onset.

A female with a BRCA1 or BRCA2 mutation is at higher risk for breast and ovarian cancer and the onset can be at a considerably younger age. However, screening is typically not performed on these women until they’re adults.

Male BRCA2 mutation carriers are at increased risk for cancers, but the risk is not the same magnitude as the risk for the women. The lifetime risk has been estimated to be around 20% for prostate cancer in a male BRCA2 mutation carrier; a female carrier of a BRCA2 or BRCA1 mutation has a lifetime risk of breast cancer that may be up to 80%.

A female BRCA1 or BRCA2 mutation carrier will be counseled and followed extensively. After they reach a certain age and have had children, they can have their breasts and ovaries removed to significantly reduce their risk.
That is what Angelina Jolie did.

Are there any other mutations that are significant for prostate cancer?

Dr. Swensen: There is a mutation
in another gene that has been shown to be a risk factor for prostate cancer: G84E in the HOXB13 gene.

This mutation is carried by about 0.5% of individuals of European ancestry. It is not a high-risk mutation. Male carriers have a two to threefold increased risk of prostate cancer. The mutation is not known to be therapeutically significant.

Is that mutation associated with an increased risk of getting prostate cancer or of getting aggressive prostate cancer?

Dr. Swensen: That has still not been clearly defined.

Does it make sense to offer prostate cancer screening earlier to men with the G84E germline mutation in HOXB13?

Dr. Swensen: It is one of many genetic factors that will influence an individual’s risk of cancer.
At this time, though, screening is not warranted.


Leave a comment

Changing PCa Screening Recommendations

Ms. Merel Grey Nissenberg, a California attorney specializing in medical malpractice cases, is the President of both the American- based National Alliance of State Prostate Cancer Coalitions (NASPCC) and the California Prostate Cancer Coalition (CPCC).

Prostatepedia spoke with her about the recent proposed changes to the US Preventive Services Task Force (USPSTF) recommendations on screening.

Not a member? Join us.

How did you become involved in prostate cancer advocacy?

IMG_3119Ms. Merel Grey Nissenberg: I’m a trial attorney. I handle medical malpractice cases.

Obviously, I don’t have a prostate. I don’t have anybody in my family who passed away from prostate cancer, but I’m very interested in prostate cancer and in cancer advocacy.

In my law practice, I’ve handled a lot of prostate cancer cases with inexcusably late diagnoses. Just shabby care. A lot of those clients have passed away because of that.

In 1994, I handled a case that had a surgical oncologist as one of our experts. He recommended that I start working on the California Division of the American Cancer Society’s Prostate Cancer Task Force, which I did.

I then went on to co-chair the task force. In 1997, there was a California-wide American Cancer Society meeting on prostate cancer. We thought it would be great to have a statewide California coalition for prostate cancer. Everybody said we couldn’t do it because California is too big. We heard that challenge. The California Prostate Cancer Coalition is now 20 years old!

Was this the first American statewide prostate cancer coalition?

Ms. Nissenberg: At that time, Pennsylvania had a coalition and Massachusetts had a fledgling coalition. A few other states were just starting coalitions.

In 2001, I went to a meeting with 20 state leaders in Washington, DC, at the former National Prostate Cancer Coalition (NPCC.) NPCC is now ZERO. We wanted to see how the states could help their organization—and how NPCC could help the states with their missions.

At that meeting, I met a lot of people from other state coalitions. I said I’d like to set up coalitions in all 50 states. Jan Marfyak, a prostate cancer survivor who was co-chair of the Pennsylvania coalition at the time, thought that was a great idea. Together, we started raising money to set up state coalitions.

In 2004, we decided to set up a national alliance, an umbrella organization, which would allow states to network with each other and to share best practices. This is now the thirteenth year of the National Alliance of State Prostate Cancer Coalitions.

Our original goal was to make prostate cancer a national healthcare priority by becoming a collaborative force that developed and mentored state prostate cancer coalitions.

In 2014, we added two core priorities: awareness and education, and public policy advocacy. To address awareness and education, we created a guide on prostate cancer screening aimed at patients and primary care physicians alike.

How have the United States government’s recommendations on prostate cancer screening changed?

Ms. Nissenberg: When I first got involved with prostate cancer advocacy, the recommendation was inconclusive whether you should screen or not. In fact, in our work, we use the word “testing” because the term “screening” is so controversial.

In 2012, which was the most recent USPSTF Recommendation, the US Preventive Services Task Force announced a straight across-the-board D recommendation: do not screen. Most physicians saw the “D” at the top of the page and never read beyond that.

But then we went back and looked. In the middle of the middle sections of the recommendations, in the Clinical Consideration section and in the Reply to Public Comments section, the Task Force clearly says that if a man wants to have an informed discussion about prostate cancer, his physician must—this is mandatory language—have that discussion with him. It is then the patient’s decision based on his own values and preferences whether or not to get tested. It was buried in the guidelines, but it’s there.

I know a lot of men have since gone for their regular physicals and have not been offered PSA testing, even though they’re getting blood drawn for other things. The issue of prostate cancer screening is not brought up. They’re not even offered digital rectal exams (DRE).

There was a huge outcry after the 2012 Guidelines became final; they did not take into account your family history, if you’re African-American,
 or if you have been exposed to Agent Orange or any other type of banned chemicals. (Agent Orange is a huge risk factor for Vietnam veterans.)

The 2012 recommendation scared men away from asking for testing. Later the California Prostate Cancer Coalition and the American Cancer Society worked together briefly to get some language into the ACS guidelines that we could both live with. We did not like the way ACS used the phrase potential benefits and harms instead of potential benefits and potential harms. (The word “potential” only referred to the benefits, not the harms.) It made the benefits only potential, but the harms certain.

Precision in language is important…

Ms. Nissenberg: Exactly. But the USPSTF proposed changes to the guidelines in April of this year; it would still be a D recommendation for men 70 and over (with no regard to life expectancy), but a C for men 55 to 69. They’re recommending that a man speak with his physician and that the physician offer the man an informed discussion about prostate cancer testing.

Based on the 2012 guidelines, physicians didn’t have to bring up testing at all. They were completely relieved of the responsibility of bringing up prostate cancer testing. Physicians felt that legally they didn’t have to discuss testing with men.

An informed discussion is not the physician telling you why you don’t want to be tested. Your physician is supposed to discuss the risks of being diagnosed with a cancer that doesn’t need treatment. He or she should also discuss the benefits:
 if you have an aggressive disease, early detection is critical.

Men need to know that this is their decision to make, based on their preferences and values. It’s not for someone else to say that you don’t need to know about this.

I’ve dealt with cases in my law practice in which the doctors actually note in medical records that the patient wants a PSA. “Patient is worried about prostate cancer.” And still some doctors have refused to test. Some of those patients are dead now. People tend to trust whatever the physician says.

It’s that old hierarchal relationship people have had with their doctors.

Ms. Nissenberg: Right. They just tend to think he or she has this superior experience, training, and expertise, so if the physician says don’t worry, the patients won’t worry.

But, as I said, physicians haven’t even been bringing testing up and have felt legally justified in not doing so.

The way I see it is that you have 
to educate, not just the primary care doctors, but also men—prospective patients—so they know to ask about prostate cancer screening. You can’t ask for an informed discussion about something you don’t know exists. We need to educate both groups.

So from the D recommendation of 2012, the proposed guidelines now say that physicians should discuss the potential benefits and risks associated with screening with men 55 to 69.

But the NASPCC and the CPCC 
have problems with the new proposed guidelines. First, why start at age 55? We advocate that a man get 
a baseline PSA in his early 40s.
 This gives a risk assessment;
 you can then personalize follow-up.

If you’re at low risk based on your PSA reading, you don’t have to come back for retesting for another five years. (No one is suggesting that men get yearly PSA tests.)

If you’re at intermediate risk, you get retested every one to two years, depending on your other risk factors.

Men at high risk would obviously need immediate follow-up.

Even the Task Force itself acknowledges in the Frequently Asked Questions section of the new proposed draft guidelines that sometimes you don’t see a benefit to screening for over 10 years. Sometimes 10-
15 years. If you wait to get baseline tests until men are 55, you lose an opportunity to prevent some of them from developing metastatic disease.

Another change in the recommendations is that the Task Force now discusses active surveillance. The guidelines say that there are men who will choose active surveillance, so those men will not be overtreated by definition. But the guidelines did not also acknowledge the fact that we now have urine, blood, and tissue markers that can help determine whether or not a man is at risk for aggressive disease. Why worry about overtreatment if a man is diagnosed, but not acknowledge the availability of biomarkers to select those at high risk for clinically significant prostate cancer?

Lastly, NASPCC and CPCC believe that Vietnam veterans and others exposed to Agent Orange should be included in the Task Force definition of a high-risk group (that currently includes African-American men and men with a family history of prostate cancer).

We do applaud that the Task Force is now finally openly talking about informed decision-making.

It’s important to remember that not everyone who is tested will be overtreated. (I don’t believe there as such a thing as overdiagnosis.) Diagnosis is just information.

You can choose not to be treated once you have the information.

Ms. Nissenberg: Exactly. You wouldn’t tell a woman, “You don’t really want to know if you have breast cancer, dear.”

After a certain age, women get mammograms yearly.

Ms. Nissenberg: Exactly. Physicians take that choice away from men.

We distribute our decision-making guide to physicians as well as patients so that they know which questions the patient is going to ask. (Men aren’t going to be coming in with 500 pieces of paper from the Internet.)

In the guide, we talk about things
 like baseline PSA, the importance of family history, ethnicity, and exposure to Agent Orange. Questions like: If I have a biopsy and it reveals cancer do I necessarily have to have treatment? What is active surveillance?

Good, basic questions and answers.

Why are they revising the guidelines now? Because of the outcry in the prostate cancer community? Or is this just part of the normal cycle of revision?

Ms. Nissenberg: It is part of the normal cycle of revision. The outcry probably helped precipitate it, but this is just their normal timeframe.

What do you feel are the greater implications of the guideline changes?

Ms. Nissenberg: The implications are that more men will hopefully be tested. More men will have that conversation and make their own informed decision about whether they want to be tested or not.

The changes to the guidelines will raise awareness at the very least.

The changes are a good start, but we’ve got to go further.

Read June 2017 Prostatepedia for more information on screening.

Leave a comment

Prostate Cancer Screening For Men With BRCA


Dr. Preston Sprenkle is an Assistant Professor of Urology at Yale University.

Prostatepedia spoke with him about a trial he’s running on targeted prostate cancer screening.

Not a member? Join us.

Why did you become a doctor?


Dr. Preston Sprenkle: My father was a physician. I liked the idea of helping people and doing something that was both intellectually challenging, yet also socially and intellectually rewarding.

I wasn’t sure, though, so after college I worked in consulting for a little while also volunteering in an ER and in some free clinics. I really valued those experiences with patients and the one- on-one interactions. I recognized how much good you can do and how much you can help someone by just listening and being attentive to their needs and concerns. Those experiences solidified my desire to go into medicine.

When I started medical school, I quickly realized that I really enjoyed anatomy and surgery. Urology is a fantastic specialty because you come in contact with a wide variety of patients—from children to very old patients, men and women. Even though most people think urology just centers on men, we actually take care of a lot of women too.

Urology involves a lot of surgeries that can be complicated and take a lot of time and energy, but there is also a lot of one-on-one patient-based care dealing with very personal things like sexual function or urinary function. Urology is somewhat unique among surgical specialties in that we not only operate on patients, but very often follow them for many years, allowing for long-term relationships with our patients.

I then became interested in cancer care. The current challenge is to improve the way we take care of cancer patients. Cancer is scary. Fortunately, in many cases it is very treatable and even curable. But hearing the C-word can be terrifying. Most people shut down and don’t really hear much after learning they’ve been diagnosed, so it can be a little longer process to help them understand that there are opportunities for cure.

What is the thinking behind the clinical trial you’re running?

Dr. Sprenkle: We opened this trial to better understand the relationship between the BRCA2 mutation, or BRCA2 deletion, in men and the incidence of prostate cancer.

There have been several studies showing that men with prostate cancer who have a BRCA2 mutation have a more aggressive prostate cancer more likely to have lymph node positivity.

What we have not been able to identify is where that starts. These men were arguably diagnosed with prostate cancer because they had an elevated PSA. Is their risk higher because they were diagnosed later in the course of their prostate cancer, or is their risk higher because the BRCA2 deletion causes them to have higher-grade prostate cancer?

When we started this trial, there was no information and no long- term prospective studies. (I believe there recently has been a trial that suggests that on a stage-for-stage basis it actually may not be much worse to have BRCA2, but that was not around when we started this trial.)

We are trying to understand the incidence of prostate cancer in this population of men with the BRCA2 mutation. This is, in part, a registry for all men who have a known BRCA2 mutation. We offer them prostate cancer screening with standard techniques: PSA blood tests, DRE, etc. But we also offer an MRI and MR-targeted biopsy to evaluate if there are any radiologic characteristics that could be used.

If 28-30% of men in a general population have prostate cancer with a PSA cut-off of 4, is that the same for men with a BRCA2 mutation?
 Or should we be screening men with this mutation earlier? Or biopsying them with a lower PSA? Do men with this mutation have a 30% rate of prostate cancer with a PSA of 2?

There is a famous trial called the Prostate Cancer Prevention Trial that used a medication to shrink the prostate. During the trial, they biopsied men 
if they had an elevated PSA and then at the end of that trial. Even men who didn’t get treatment were biopsied
 at the end, independent of what their PSA was. The trial gave a tremendous amount of information about what the likelihood is of developing prostate cancer when your PSA is as low as 1. Based on the results of this trial,
 we know that approximately 8%
 of men with a PSA of 1 or less have prostate cancer on a random biopsy—even though we typically don’t biopsy those men.

This current trial is an opportunity
 for us to gain information about how—or if—the incidence of prostate cancer is different in a population of men with a BRCA2 mutation.

Are you just looking for men without prostate cancer with the BRCA2 mutation?

Dr. Sprenkle: Yes. Any man who
 has at least a 10-year life expectancy qualifies to be screened.

Subscribe to Prostatepedia to read the rest of the conversation.