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Conversations With Prostate Cancer Experts


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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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Dr. Charles Ryan: Why Oncology?

Dr. Charles J. Ryan is the Clinical Program Leader for Genitourinary Medical Oncology at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

He primarily treats men with advanced prostate cancer. His research focuses on novel therapies for advanced prostate cancer.

Not a member? Join us to read Dr. Ryan’s conversation in our March issue on cancer recurrence.

Why did you become a doctor?

Dr. Ryan: I grew up in a medium-sized city called Appleton, Wisconsin. My father was the first medical oncologist and the first prescriber of chemotherapy in our town. He never did a fellowship because they didn’t exist when he finished his training.

I’m the youngest of four kids. By the time I was in junior high school, all of my siblings had gone away. My mother is a nurse, and she was working for hospice in our community. Sitting around the dinner table, it was just the three of us.

The dinner conversation was frequently about cancer, hospice, medicine, and things like that. That’s what shaped me at the time. I decided to become a physician in college, but I had given a lot of thought to oncology and medicine well before making the decision.

I guess medicine is the family business?

Dr. Ryan: Yes. It is sort of a family business. When I started my medical training, I felt a kinship with the medical oncologists I interacted with at the University of Wisconsin. I was randomly assigned to work in an oncology clinic and a prostate cancer clinic. I just felt like: these are my people. The timing was right for me to make a decision. It’s what I wanted to do with my life. I found the disease itself biologically compelling, and the emergence of new therapies and the community of physicians and researchers who worked on it were an interesting group of people. It was a natural decision.

Join us to read Dr. Ryan’s thoughts on Xtandi (enzalutamide) and Zytiga (abiraterone.)


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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


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Imaging + Prostate Cancer Recurrence

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

Prostatepedia spoke with him about imaging recurrent prostate cancer.

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Prostatepedi:Some imaging occurs when men are first diagnosed. When, after treatment, do they encounter these newer imaging techniques? After a high PSA reading? Or just a part of routine follow-up?

Dr. Philip Koo: That’s a really tough question because imaging has a role throughout the continuum of care for any prostate cancer patient. Screening currently isn’t done with imaging, but there are a lot of research studies looking at it.

Prostate MRI is most often used for the detection of local disease. Oftentimes, patients with a rising PSA and a negative standard biopsy might get an MRI or an MRI-guided biopsy.

Bone scans and CT scans are used to help detect metastatic disease. There are many different scenarios, but usually after patients are diagnosed with cancer, most will visit radiology if there is a suspicion for metastatic disease. If we refer back to the RADAR 1 paper published in 2014 by Dr. Dave Crawford in Urology (see Urology 2014 Mar; 83(3): 664-9), we talk about imaging patients at initial diagnosis and imaging those who are intermediate or high-risk. In those patients, we recommended a bone scan and a CT scan.

Patients who are biochemically recurrent may also be imaged. Again, MRI will often be used to look for locally recurrent disease. Bone scans and CT scans are used to look for metastatic disease.

What about some of the newer imaging techniques?

Dr. Koo: The newer techniques are exciting. In both the patient community and the scientific community, we’ve heard a lot about these tools over the past decade. They weren’t widely available, especially in the United States. These newer imaging tools are simply better, which is why there is so much excitement. They will pick up more sites of disease at lower PSA levels.

When we do detect sites of disease, they’re more specific. Our confidence that these sites are actually disease is higher than our confidence when we’re using traditional bone and CT scans. These tests perform at a higher level compared to standard imaging.

Another benefit to these new tools is that in one single exam, we’ll be able to detect soft tissue and bony disease.

How do these newer techniques change treatment? If you can pick up the disease at a lower PSA is that going to change how a doctor treats a man?

Dr. Koo: Yes. We will be able to detect disease sooner. Currently, these newer imaging techniques are used mostly in patients with biochemical recurrence. When a patient has biochemical recurrence and we see the PSA rise, our standard imaging techniques are often not good enough to detect metastatic disease. The problem is that the radiation oncologist or the urologist needs to decide how they want to treat the patient.

Using these newer tools, we can provide the urologist or radiation oncologist with better information about whether or not the disease has spread at the time of biochemical recurrence. If it has not, and the urologist can perform salvage cryotherapy or a radiation oncologist does salvage radiotherapy, we could potentially cure the patient.

Really?

Dr. Koo: You’re hitting the disease before it spreads, so theoretically yes. These newe imaging techniques do better, but we really need to prove why this is important and how this impacts care. The answers to these questions will solidify the utility and value of these imaging techniques for prostate cancer patients.

If a patient gets the Gallium-68 PSMA or Axumin scans will his local urologist or oncologist know what to do with that information?

Dr. Koo: Maybe. The problem is that all of this sounds great: we have a tool that can detect disease sooner, better, and more accurately. But then the more important question is what to do with that information and does it impact outcomes. If we don’t know, then what is the value of that imaging tool? We operate under the assumption that earlier detection is always better, but we’re learning that in a lot of diseases that is not always true.

We could be over-diagnosing and over-treating certain diseases. Whether it’s imaging, urology, radiation oncology, or oncology, it really is a team effort because we all bring something unique to the table. We really need to work together to make sure we come up with the best plan and the best answers.

Join us to read the rest of Dr. Koo’s comments on imaging recurrent prostate cancer.


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Prostate Cancer Recurrence

Dr. Alicia K. Morgans is a medical oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. She specializes in treating advanced prostate cancer and is particularly interested in addressing treatment side effects.

She frames Prostatepedia’s March conversations about prostate cancer recurrence.

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One of the most common questions I’m asked as a doctor who treats prostate cancer is: what happens to me if my cancer comes back? This is always a difficult conversation, especially because people often ask it in the presence of their family members. A man’s wife or child is also really interested in knowing the answer to the question. The question is often driven by anxiety and fear in men who have already undergone what can be a life-altering treatment experience. They’re trying to look ahead and plan for their future. But there are many parts to any possible answer.

First: what do you go through to monitor before the cancer comes back? After treatment, we follow a man’s health, watch his PSA intermittently over time, and often do imaging studies.

If the cancer comes back, the first sign is often that a man’s PSA starts to rise. At this point, we typically use imaging studies to understand what the disease is doing. Even when the PSA is really low, our new imaging technologies can show us where the cancer is and help us determine how a man’s recurrence may be ultimately treated—whether that is with local or systemic treatment. Again, this is a really anxiety-laden situation. We’re fortunate to have these new exciting imaging technologies for patients and their clinicians, which Prostatepedia discusses at length in this edition.

We use these imaging technologies in men with biochemical or PSA-only recurrence to help us understand where the cancer is located. For some men, these new imaging techniques might show us that there is a cancer recurrence in the pelvis where radiation can be given to potentially cure them of recurrent prostate cancer. That is a huge win, progress for our patients, and of course, wonderful news for the men and their families.

For other men, it is possible that we will not necessarily find recurrence, even with new imaging techniques. In those cases, we often continue to wait and watch. Biochemical recurrence can be challenging psychologically because knowing that your PSA is rising can be stressful, and the data explaining the best approach to treatment is not complete.

For men who have a single area of prostate cancer that has come back, whether as a single bone lesion or a few locations, advances in therapy for oligometastatic disease have come fast and furious. In this issue, Dr. Piet Ost talks about oligometastatic prostate cancer and how we might use radiation or surgery to treat a small amount of recurrent prostate cancer. Several clinical trials are working hard to figure out if treating this low volume of prostate cancer in single areas will potentially cure men of recurrent cancer.

It’s really important that we have new treatments we can use for men with hormone-sensitive metastatic prostate cancer, too. Over the last few years, we’ve seen men with metastatic hormone-sensitive prostate cancer live well for many years with several options for treatment. New data describing chemo-hormonal therapy or androgen deprivation therapy (ADT) with Zytiga (abiraterone acetate) have been incorporated quickly into clinical practice and are being widely used to help men with metastatic hormone-sensitive prostate cancer live longer.

Unfortunately, sometimes a man’s prostate cancer comes back more broadly, as a rising PSA only, or with sites of metastatic disease. This can be challenging physically, because sometimes it’s coupled with fatigue or pain as well as emotional difficulty. The cancer that a man thought was gone has now come back. To address this, there are many scientists and physicians working to try to help men with prostate cancer live better by using therapeutic advances as well as psychosocial and pain support teams that can improve patient-reported as well as disease outcomes. By incorporating social work and psychiatrists, centers are able to support men and their families, helping patients cope with PSA anxiety, which is an issue that can be anxiety-provoking and potentially go on for years at a time.

In terms of therapies, we as a field are very excited about new data that offers new therapies to men with biochemical recurrence who develop castration resistance before they have radiographic evidence of metastatic disease. Two clinical trials presented last month in San Francisco at the annual ASCO Genitourinary Oncology Symposium suggest that using either Xtandi (enzalutamide) or Erleada (apalutamide)—both androgen receptor-directed therapies—can prolong metastasis-free survival for men with castration-resistant non-metastatic disease.

This is a valuable advancement because any day spent without metastasis is a day spent feeling stronger and with less pain. We are also excited because both of these oral drugs have relatively low toxicities. Both clinicians and patients win when we add a significant amount of metastases-free time with a few pills and minimal side effects.

As a clinician, I understand the anxiety that drives the question: what if my cancer comes back? But this is a time of incredible hope. Medical advances are helping men live longer and live better, even if their cancers do come back.

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


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Advances in Medical Oncology

PetrylakDr. Daniel P. Petrylak, Professor of Medicine and Urology at Yale School of Medicine, has been a pioneer in the research and development of new drugs and treatments to fight prostate, bladder, kidney, and testicular cancers.

Prostatepedia spoke with him about advances in medical oncology for prostate cancer.

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What are the current points of controversy and/or trends in the field of medical oncology for prostate cancer?

The first controversy is over localized disease. There are really two forms of prostate cancer. There is the nonaggressive form that is not going to be lethal and that you’ll die with and not from. Then, unfortunately, there is the lethal form of the disease that kills about 30,000 men a year in the United States. The controversy is how do you treat these patients? How do you decide who to treat and who not to treat?

For advanced metastatic disease, there are controversies over the right treatments, the right sequences of treatments, when to use other hormones, and when to use other chemotherapies. There are a lot of questions that need to be answered.

Unfortunately, prostate cancer has always been behind other tumors. If you look back to the 1990s, there was about five times less funding for prostate cancer than breast cancer. We were behind in funding compared to other tumors, but have made significant strides in increasing money available for research.

We’re catching up in the area of personalized medicine. We didn’t really have markers a couple of years ago. But now we’re beginning to see markers—whether that be with BRCA mutations, BRCA-like mutations, or AR-V7—employed in the treatment of advanced metastatic disease to help select therapies. These approaches are in the advanced stages of development and have yet to be approved by the FDA. Those are the major controversies.

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