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Conversations With Prostate Cancer Experts


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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.

Subscribe to read the rest of this month’s conversations about prostate cancer recurrence.


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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.

Subscribe to read Dr. Ost’s comments on oligometastatic prostate cancer.


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Zytiga + Xtandi For Prostate Cancer

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.

How do Xtandi (enzalutamide) and Zytiga (abiraterone) work? What are the differences between them?

Dr. Ryan: Xtandi (enzalutamide) and Zytiga (abiraterone) have been out on the market for a few years. They are both considered standard therapies in castration-resistant prostate cancer. The hormone receptor interaction is important throughout the progression and natural history of the disease. They are similar, but they are not identical in terms of their mechanism of action.

Zytiga (abiraterone) lowers the levels of androgens; it lowers the levels of testosterone and related molecules that are available for the cancer. Xtandi (enzalutamide) blocks the androgen receptor in a potent way. They both end up reducing hormone signaling in the disease.

Because they have different mechanisms of action, they have different side effects. The generic name of Xtandi is enzalutamide, similar to apalutamide (currently in development). They were invented in the same laboratory at University of California, Los Angeles.

Are they all used in the same set of patients?

Dr. Ryan: For the most part, yes. The initial approvals of the drugs for the disease were in patients with metastatic castration-resistant disease in post-chemotherapy patients (CRPC). Then there were two studies that tested Xtandi (enzalutamide) and Zytiga (abiraterone) respectively in chemotherapy-naïve CRPC patients. Both of those demonstrated a benefit over placebo in terms of delaying the disease, the onset of symptoms, improvements in survival, and a decline in functional status. Now they are standard of care for CRPC patients.

Recent reports of the LATITUDE and STAMPEDE studies done in Europe and Canada demonstrated that Zytiga (abiraterone) offers a survival benefit to patients when added to initial hormonal therapy, so that is a new standard for Zytiga (abiraterone). Similar studies with Xtandi (enzalutamide) are ongoing and could demonstrate a similar result, which is to say, Xtandi (enzalutamide) could be used up-front in initial hormonal therapy.

That’s a big change.

Dr. Ryan: That would be. Yes.

Are some men resistant to these therapies initially, or do they develop resistance? If so, is there any way of telling whether a man will be resistant?

Dr. Ryan: In terms of resistance to these therapies, it is fairly universal that patients will develop resistance to these therapies when they receive it in CRPC. Most CRPC tumors have mutations of one type, and some of them have many mutations that ultimately render them resistant to various therapies. One of the big challenges in the field over the last few years has been this question of whether these two drugs are so similar that we should simply choose one and use it, or whether we can use them in a serial fashion. In other words, we would treat a patient with Zytiga (abiraterone) until the disease becomes resistant, and then treat with Xtandi (enzalutamide).

Overall, the use of the second one of these is less effective. It’s probably best to choose one and, if it’s tolerated well, stick with it. When a patient becomes resistant to one of these drugs, using the other one may be of limited value.

There’s no way to reverse or combat a man’s resistance?

Dr. Ryan: It’s actually quite complicated. In the laboratory, the androgen receptor and the factors that stimulate the androgen receptor are dynamic. It is possible that prostate cancer cells could become re-sensitized to these. There are some experimental suggestions that that could occur.

However, we haven’t really seen that bear out in the clinic. It’s a rare patient who will develop progressive disease on Xtandi (enzalutamide) and then have a significant benefit to Zytiga (abiraterone), for example.

You touched briefly on combining drugs in this class with other types of therapy. Are there any others that appear more or less effective?

Dr. Ryan: The results of studies where Xtandi (enzalutamide) or Zytiga (abiraterone) were combined with other therapies are disappointing. At our center, we have tried to do a couple of these combination studies and have not seen results that would change the standard of care. We don’t combine them with chemotherapy, typically.

There was a study that combined Zytiga (abiraterone) with Xofigo (radium-223); that study closed early due to excessive deaths and fractures. It looked like that combination may be dangerous. We’re not sure why that is. Some more thought is going into that process. There is a study underway that’s maturing, which is a combination of Xtandi (enzalutamide) and Zytiga (abiraterone). We anticipate results in the coming year.

For the time being, these should be given as single agents, not in combination.

Has anybody looked at combining them with immunotherapeutic agents?

Dr. Ryan: The newer PD-1 inhibitor immunotherapies in prostate cancer are probably only active in a small proportion of patients with prostate cancer. And there are some studies underway with those, but no definitive data yet.

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


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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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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.