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Conversations With Prostate Cancer Experts


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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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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.)


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Dr. Piet Ost: Why Medicine?

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 what drew him to medicine.

Why did you become a doctor?

Dr. Piet Ost: It was a bit by coincidence. I planned to be an airline pilot, but due to some medical issues with my eyes, I was not allowed to fly. I’ve always had a big interest in anything scientifically sound where you can start with science and build up from there. I found evidence-based medicine interesting from the beginning. So I started an alternate plan to become a doctor. I enrolled in medical school and became more interested in getting patients involved in the science, in applying evidence-based medicine. How can we do that? Where are the big gaps in science?

In medical school, I realized that there are so many unanswered questions that patients ask on a daily basis. You just have to tell them what we know now, but that there are many things that we still do not know or fully understand. That communication process has helped me a lot in talking to patients. They helped me grow in this process once I graduated.

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Salvage Radical Prostatectomy

Dr. James Eastham, Chief of Memorial Sloan Kettering’s Urology Service, is a surgeon who specializes in nerve-sparing radical prostatectomy and salvage radical prostatectomy.

Prostatepedia spoke with him recently about surgical options when cancer comes back after initial treatment.

Can you define salvage radical prostatectomy for us?

Dr. Eastham: A salvage procedure just means something failed beforehand: a salvage radical prostatectomy is surgery done on a prostate that has been treated with something else. That something else can be radiation. It can be prior high-intensity focused ultrasound, meaning the patient had a heat application to the prostate to try to treat prostate cancer. The something else can be cryotherapy that was unsuccessful. But basically, salvage surgery means surgery after a failed non prostate-removing technique.

In what scenario would a man encounter salvage surgery: after a couple of high PSA readings? After another biopsy? After an imaging study?

Dr. Eastham: Most of the salvage surgeries that are done are still done for patients who fail radiation therapy.

A patient underwent radiation therapy for prostate cancer. They’re followed, and then their PSA blood test starts to go up. Typically, as part of the evaluation for a rising PSA after failed radiation therapy, the patient will undergo imaging studies.

There are different imaging studies that we can do to check if there is any evidence of cancer beyond the prostate. If all of those studies are negative, then the patient will typically have a biopsy of his prostate. If that biopsy shows persistent prostate cancer, the patient is at least a candidate for additional local therapy, meaning therapy directed at the prostate. All of these therapies are called salvage. Surgery to remove the prostate is a salvage prostatectomy. Some patients may have cryotherapy. That’s salvage cryotherapy. Patients can have radiation after failed radiation. That would be salvage radiation therapy. There are a variety of options.

Is any of this controversial? Or are there any men in whom this kind of approach might be controversial?

Dr. Eastham: The patient should have a cancer that was potentially curable with local therapy at the time of the original diagnosis. The cancer at the time of treatment failure must still be potentially curable with local therapy.

There are some patients who, at the time of their original diagnosis of prostate cancer, had a big, bulky cancer that was treated with radiation therapy and subsequently failed this treatment. These patients really aren’t appropriate for salvage radical prostatectomy because they were never surgically curable.

To be a good candidate for salvage local therapy, including salvage prostatectomy, the patient would have to have been diagnosed with clinically localized, non-metastatic cancer, have undergone a treatment that didn’t work, and after initial treatment failure, still have a clinically localized, non-metastatic cancer amenable to local therapy.

As our imaging techniques become more and more refined, are we identifying these recurrences earlier? Does that have any kind of impact on who gets a salvage prostatectomy or not?

Dr. Eastham: Most of the follow up is still done with PSA, so routine imaging is typically not done after prostate cancer treatment. Most of the treatments are still based on waiting for a PSA to rise. A rising PSA typically leads to other testing. This other testing has become more sensitive in picking up patients with low-volume metastatic disease. That is where the imaging matters.

If someone already has metastasis, as shown by whatever imaging study, it’s unlikely that salvage radical prostatectomy is going to provide them with any particular benefit because this is a big surgery and has potential risks. That is where the imaging comes into consideration. Imaging looks for metastatic disease and basically excludes patients who won’t benefit.

Is salvage radical prostatectomy a trickier procedure than an initial prostatectomy?

Dr. Eastham: Absolutely. Any prior treatment to the prostate results in the development of scar tissue.

After radiation therapy, high-intensity focused ultrasound (HIFU), or cryotherapy, scar tissue develops. The prostate fuses to organs from which it would typically be easily separated.

The primary concern is the rectum; injury to the rectum is a potentially devastating complication of salvage radical prostatectomy. All of the tissues tend to not heal as well because the scar tissue has an impaired blood supply. There is slower healing. The anastomosis, where we sew the bladder and the urinary tube back together, also tends to heal more slowly. This can lead to a higher risk of urinary leakage, or anastomotic leak. There are higher risks of strictures, or bladder neck contractures, which is scar tissue that develops where the bladder and urinary tube are sewn back together. When that happens, the man just basically can’t urinate. There is much higher risk of incontinence.

Again, the radiation therapy results in scar tissue, so things just don’t heal as well as they should. On top of that, it’s very difficult, even in those men who still have erectile function after radiation therapy, to preserve erectile function in men undergoing some type of salvage surgery. It’s just a far more difficult operation for the surgeon. But from the patient’s perspective, there is a much higher risk involved in terms of side effects and negative consequences.

Is it in a man’s best interest to find a surgeon who has done a lot of these salvage procedures?

Dr. Eastham: Yes. This is not something that is typically undertaken by someone who doesn’t have much experience in terms of doing traditional radical prostatectomy. The surgeon needs a bit of experience and has hopefully been trained in dealing with post-radiation tissue changes.

Do you have any other advice for a man facing salvage radical prostatectomy?

Dr. Eastham: The issue is always: how curable is his cancer. The tendency after radiation therapy is to watch patients’ PSAs rise for much longer than is clinically beneficial. The traditional definition of failure is the lowest PSA the man achieves plus two; this is called the Phoenix definition. Waiting for the PSA to rise two whole points just gives the cancer a chance to grow. But the earlier one treats prostate cancer, the better.

Waiting until the PSA is nadir plus two is too long for the patient to still be an optimal candidate for salvage treatment. The earlier the better. A man with a rising PSA after radiation, even if his PSA hasn’t yet reached nadir plus two, should be considered for imaging studies and potentially a biopsy.

Not a member? Join us to read the rest of this month’s conversations about cancer recurrence.

Members can read all of this month’s conversations in their March issue of Prostatepedia.


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Dr. James Eastham: Why Medicine?

Dr. James Eastham, Chief of Memorial Sloan Kettering’s Urology Service, is a surgeon who specializes in nerve-sparing radical prostatectomy and salvage radical prostatectomy.

Prostatepedia spoke with him recently about surgical options when cancer comes back after initial treatment.

Why did you become a doctor?

Dr. James Eastham: I didn’t decide to become a doctor until my third year of college. I was a chemistry major.

I had worked in the laboratory and thought I wanted to work more with people. I had a science background and lots of friends who were pre-med. They thought that being a physician would be something that I might enjoy, so I took the appropriate classes and exams and was fortunate enough to get into medical school.

That is how I became a doctor.

Why did you choose surgery as opposed to another specialty?

Dr. Eastham: I enjoyed the care of surgical patients. I was very interested in anatomy and how the illnesses that require surgery were, in many ways, based on anatomy. I liked the technical aspects of doing surgery. I liked the hands-on approach and the anatomy that is involved.

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Subscribers can read Dr. Eastham’s conversation—as well as all of the other conversations, in their March issue of Prostatepedia.


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Advanced Imaging + Prostate Cancer

Dr. Phillip Koo is Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center.

Prostatepedia spoke with him about advanced imaging + recurrent prostate cancer.

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Do you have any advice for men considering advanced imaging for prostate cancer?

Dr. Koo: We’ve been talking about better imaging tools for prostate cancer for years. When it comes to other cancers, we moved forward a great deal when FDG PET/CT became available. With prostate cancer, we’ve been stuck with CT and bone scans since the 1970s. They’re great tools. I don’t want to devalue what they’ve done for our patients since then, but we knew we could do better. Urologists and oncologists knew patients had metastatic disease, but our imaging tools limited detection.

We have new tools available to us in 2018. There is no question that costs are going to be higher, but that shouldn’t stop us from exploring and pushing the envelope. The whole purpose is to improve overall survival and treatment for our patients. An ounce of diagnosis could be a pound of cure. If we could identify disease sooner, identify the right patient for these exams, and use them at the right time, then we could probably create treatment plans more appropriate for patients with better outcomes. It’s something that I firmly believe. There is so much potential here.

When radiology is practiced in a vacuum, it’s not as powerful as when it’s integrated into patient histories and treatment plans. Radiology is a very powerful tool. But we often think of it as a commodity, something that does not have any distinguishing value. That is a huge under-estimation of radiology.

When performed correctly in a multidisciplinary setting, with access to the medical record and physicians who are taking care of the patient, radiology unlocks information that can really impact care for patients with prostate cancer. And we are currently only scratching the surface. This will change as analytic tools continue to analyze bigger data sets that include imaging and clinical data. If a urologist determines that their patient needs imaging, they’re going to write a request for imaging that describes what type of test they want and why they need it.

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Patients often go to the closest facility. Convenience is important, but when it comes to certain tests or exams, I urge patients to seek out subspecialized radiology experts and facilities with the experience and expertise in the performance and