Redefining Advanced Prostate Cancer with Novel Imaging - Episode 10
Raoul S. Concepcion, MD, FACS: That’s a great segue. Essentially, in this patient that we’re talking about, we assume that the scans are negative. Alec, you brought up the point—that we know, based upon some of the studies that have been done—that even though they’re asymptomatic, we know that about a third of these patients may actually be harboring undiagnosed metastatic disease. They’ve gotten scanned. The scans are negative, based upon bone scan CT. So, this would be Index Patient 1 in the AUA guidelines, or M0 nonmetastatic castration-resistant prostate cancer. Dan, as we sit here, right now, not projecting 3 months from now but right now, what are the options for that patient?
Daniel George, MD: This has been one of our unmet needs in the field. This is a patient that we’re going to sit across the table from and talk to about their rising prostate-specific antigen. We’re really not going to have any therapy that’s proven to benefit them. Yes, there are anti-androgens that we’ve been historically using, like bicalutamide or flutamide, but they’ve never shown a clinical benefit in this setting. And so, we’re modulating PSA. That’s it. There have been studies that have looked at targeting bone with denosumab. This has shown a modest effect in delaying the time to metastasis, but it didn’t meet the bar for the FDA. And so, we’re kind of left with an unmet need, an opportunity to say, “We can look harder for this cancer, but we know that PSA is an indicator that the cancer is waking up from your hormonal therapy.” It’s castrate resistant, as Neal has outlined.
There are a few markers that help us decide who’s really at risk for developing early metastasis. PSA levels that are over 10 are at higher risk. PSA doubling times, particularly PSA doubling times of 6 months or less, are at particular high risk for developing bone metastasis in the next year or two. So, by looking at those markers, we kind of know who we can sit and watch for a while. If they have a PSA of 0.2, maybe it’s occurring slowly. We kind of know who is likely to develop metastatic disease that’s grossly metastatic in the next year or two.
I kind of cringe at this term of “nonmetastatic castrate-resistant prostate cancer” because it’s a terrible misnomer. Most of these patients have had their prostate out. There is no primary. We know that this is metastatic disease. It’s not radiographic metastatic disease. We probably need to explain that more. To me, the nonmetastatic castrate-resistant clinical trials that we will talk about are really low-volume metastatic disease studies. I just want to make that clear, because I think the nomenclature is really misguiding.
Raoul S. Concepcion, MD, FACS: Those are great points. I think that the audience does really need to understand that in those patients—as you appropriately stated, historically, based upon some data—we are going to flip their scans. They’re going to go positive. So, that being said, before we start launching into some of the stuff that’s just been presented, Alec, when you get those patients, I’m assuming they all get shunted into your Advanced Prostate Cancer Center?
Alec Koo, MD: Yes.
Raoul S. Concepcion, MD, FACS: How does the monitoring scheme change for those patients? Many of them are probably on every-6-months follow-up. Depending upon their shots, every 4 months. But, when you start to see this, do your monitoring schemes change? How often are you scanning? What lab work are you getting?
Alec Koo, MD: First, I have a question. It’s probably for Phil. So, here I am, Joe, the urologist in the community. Fluciclovine became available. I know there’s no first level evidence for use in this setting, but there’s this temptation to use fluciclovine to see if I could, in fact, identify metastases and then reasonably institute treatment. What is the weakness in that?
Phillip Koo, MD: There is no weakness. If you actually look at the label for fluciclovine, it just says, “elevated PSA following prior therapy.” It doesn’t say, “prior definitive therapy.” It doesn’t say, “distinguish the different disease states.” So, you’re right. I think that falls under the label. To me, if you’re willing to image and act on the results of that imaging, then I see no problem with that. Because, as we heard, these patients have metastatic disease. Even though the trials talk about M0, we know they’re out there. It’s just a matter of what tool you’re using. So, if this is a way that you can get a patient into that M1 space to officially start treatment, I think there could be value to that. That’s an area that we need to look at and figure out. We have to go back to this idea of combination or layering. What are the best ways to treat these patients? And how do we use imaging as a tool?
Alec Koo, MD: That being said, we’re not doing that, routinely. Even without our system, there’s still a lot of variation in care. The care is systemized in a fashion where the navigator in the system interacts with the individual urologist. But there’s still a certain amount of variability regarding what the urologists choose to do. So, it’s a transitional time. We hope to at least be able to obtain PSA and testosterone every 3 months, if not every 6 months. Alkaline phosphatase is often helpful in this setting. And then image based on the RADAR guidelines.
Transcript Edited for Clarity