Challenges in Treating Nonmetastatic Castration-Resistant Prostate Cancer

Transcript:Raoul S. Concepcion, MD: In this next segment, this first part, we’ve concentrated a lot on timing and the use of androgen deprivation therapy (ADT), concentrating primarily, again, in what I fundamentally believe is the largest use of ADT, which is in the biochemically recurrent space, especially in the urology world. So, as we move forward now in the disease state, Jorge, I think you mentioned earlier that we all know that despite ADT, a subsegment of these patients is going to progress to castration-resistant prostate cancer (CRPC).

We have spent a lot of time in previous episodes and previous segments. You cannot pick up a journal article, you can’t go online without seeing some new advance on newer therapies, molecular drivers in the metastatic castration-resistant prostate cancer space. Dan, moving to you for a second, you got a very robust advanced prostate center. You do clinical research trials in a community practice, which I think is great. As you have these patients who are on ADT, especially the high-risk ones, when do you, as the director of the center, start to encourage your partners to say, “Hey, listen, maybe we need to be a little bit more aggressive in trying to identify metastatic disease”? What are your triggers? Do you have triggers? Do you follow a guideline that helps the viewers to say, “If I’ve got somebody on ADT and my PSA is starting to go up, when do I start imaging?”

Daniel R. Saltzstein, MD: That’s a great question, Raoul. Again, in my practice, I try to communicate to my partners. We tend to use the RADAR guidelines, and they’re soft guidelines, but it is a panel of experts that got together and looked at the data to determine the risk of metastatic disease, when they were going to show up with metastatic disease. And, again, it’s to start imaging when that first PSA hits 2, to start with a bone scan and a CT scan. Again, if you find that they still have nonmetastatic disease (M0) in our group, we put them on a clinical trial; avoid Casodex. But then, again, we tend to keep a closer eye on these folks. Maybe it’s an every-2-month PSA, testosterone; it might be every 3 months. But when they get that first doubling time—I use 4 and think the RADAR criteria is 5—then we would probably image them again. If they have a really rapid doubling time and I had a very high index of suspicion that I’m missing a metastasis with the older technology, in San Antonio, I would probably get a sodium fluoride PET CT and then I would do it on an every-other-doubling time. At least in my community, it’s a little bit challenging to get that sodium fluoride PET as far as documentation, getting a specific radiologist that you trust to interpret the data, those kind of things.

Raoul S. Concepcion, MD: Alicia, is that what the Vanderbilt advanced clinic does?

Alicia K. Morgans, MD, MPH: I would say we do the same thing, and I would echo the challenges with getting some of those advanced imaging techniques. We’re lucky that we do have partners in the community who are able to get those and others in the community who have tested these radiologists time and time again with many scans. Because I do think it’s something that they need experience with because they can be so sensitive. We really need to know when they’re truly positive and not find false-positives in these patients. But I would say we do just the same thing.

Ashley E. Ross, MD, PhD: Just one thing. For the future and for the way payers are going to look at these scans, I think if we look at other malignancies and how PET was used, there was a bit discouraging of serial molecular imaging, and I think part of that was due to the cost being much more than dose or anything like this. And so, that’s been plaguing us as well. Some of these newer modalities, once you know where the lesion is on your sodium fluoride PET, you can have your radiologist go back and really find it on conventional imaging. So, if we do start using them, I think that one of the practice patterns we’ll see is a baseline at time of concern, that there actually is disease present, and then the follow-up will be with conventional imaging.

Jorge A. Garcia, MD: I agree with that, but I do have some concerns. Within the consensus of the guideline, specifically a guideline for research studies, we continue using conventional technetium-99 bone scans and CTs of the chest, abdomen, and pelvic region. For those physicians who do not use ADT for rising PSA syndrome, M0 is not a disease that exists for them. For all of us, if we use ADT for rising PSA, we may capture a subset of those patients who may have actually M0 CRPC. I tell my patients, and I just try to be quite practical about this that at the end of the day; I don’t chase numbers. So, I tell them their quality of life, their symptoms, or if they’re off from their disease, what kind of side effects I’m going to induce. I say, “I’m going to have to put you on treatment that can cause detriment to your quality of life. This is what your scans are telling me and this is what your PSA absolute value and doubling time are.” I use those features in that sequence and in that order to make my treatment choices. I only scan patients when I’m going to do something treatment-wise. I don’t scan people just to scan people.

Now, if you were to do a scan baseline, one of the challenges is if you have a patient on a trial and you get a PET fluoride, a PET choline, or a PSMA PET, you cannot revert back. And that’s one of the challenges that you or I may experience. Even at the clinic, it’s very hard to get a sodium fluoride PET approved. You have to be over 65 or you have to be part of the PET registry program. And it’s challenging because if you got technetium-99 and it’s negative, and you come back with that fluoride PET, what are you going to do? You cannot go back and do a technetium-99 again because you’re going to have no disease that you’re going to see.

And yet, again, another challenge we continue debating is timing for treatment. Does timing really matter? Now, I have changed my practice because if you look at the European data—at least the data that are retrospective in nature—the outcome of patients with 1 or more bone lesions at 5 years, less than 3% of those men are alive. So, that’s huge. To some extent, I do want to recognize and identify early metastases because I think we can treat those patients with life-prolonging treatments. Bu, the timing is really not well defined, and that’s one of the challenges that we face.

Raoul S. Concepcion, MD: Right. I think with all the new agents that have been approved since 2010, there’s no question that all of us believe in earlier identification, which was the whole basis of the RADAR working group. And Dan, as you mentioned, this was a consortium of academic and community medical oncologists, urologists, and radiation oncologists that came up with what made sense. Because the guidelines don’t really give us that. AUA, NCCN, ASCO, they don’t really tell us when to start imaging. So, what’s frustrating, as you said—and all of us do trials—is that we’ve got all these cool scans, but all the trials continue to be based upon traditional technetium nuclear medicine bone scan and CT. Again, I think that this is going to be a challenge for all of us. I think all of us would agree that we would love to have some of these agents earlier on. I think the concept we know, that the true M0 patient, it’s clinical trial or observation. We know from all the data, that if they truly are negative on bone scan CT, that within 2 years, 46% develop a radiographic bony metastasis. I think all of us want to believe that if we could impact the disease with lower PSA levels, it makes intuitive sense that they should do better. And I think that’s why we’re starting to see a lot of these, now, trials in M0 because I think everybody is wanting, as you said, Ash, to get these drugs earlier in the disease state.

Transcript Edited for Clarity