Management of Advanced Prostate Cancer in Urology: Update on Androgen Receptor Inhibitors - Episode 12

Role of PSMA PET in Advanced Prostate Cancer Management

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Experts in prostate cancer review the role of PSMA PET imaging in advanced prostate cancer and its impact on disease management.

Neal Shore, MD, FACS: Getting back to the PSMA [prostate-specific membrane antigen] PET [positron emission tomography], the 18F-DCFPyL [Pylarify] was approved in the United States in May. The first dose was given in June, and multiple states have access to it. The folks rolling this out at Lantheus are doing a great job. There’s Medicare reimbursement in several states. The competitor PSMA PET, the gallium [Ga-68 PSMA-11] by Telix, is probably going to get FDA approval by the end of 2022, certainly by end of first quarter. I can’t imagine a state that’s not going to have PSMA PET capabilities. There are some differences in the molecular agents or generators vs cyclotrons, but that’s another conversation.

Ash, you were talking about a nice paper by Wolfgang Fendler and Dr Boris Hadaschik that was published in CCR [Clinic Cancer Research]. They took 200 patients who qualified for the SPARTAN, PROSPER, or ARAMIS, with negative conventional CT scan who all had PSMA PETs. Lo and behold, 99% found that 45% had disease confined to the pelvis and 55% above, but their technetium scan and bone scan and CT were negative. Ash, would you do anything different if you have that patient now, tomorrow, or in 2022? How will you treat that patient?

Ashley E. Ross, MD, PhD: There were 2 important things that paper stated when I put it all together for myself. As a urologist, I was an early utilizer of PET PSMA because it was being developed by Marty Pomper and others at Johns Hopkins University, and we had early access. I’d always think about the BCR [B-cell receptor] space, and we’d be thinking about spot welding these metastases. The nmCRPC [nonmetastatic castration-resistant prostate cancer] space or the PET-positive or the metastatic space in the CRPC [castration-resistant prostate cancer] spending is different. What ARAMIS, SPARTAN, and PROSPER teach us is that those people need systemic therapy. They’re not on the phase 2 ORIOLE trial or other ones you could spot well. They need systemic therapy to benefit.

One thing is I will scan those guys. If you recall, about 198 of 200 had a finding, but 25% had a finding where only the prostate or the pelvic bed lit up. I found that very interesting, and maybe a role for some of those guys for local therapy if they haven’t received it. In the other settings, if there’s metastatic disease, it helps me think about what agent I would reach for next. Technically, you could say that guy has mCRPC [metastatic CRPC], but I probably wouldn’t say to use docetaxel. That’s the guy who qualified for SPARTAN, ARAMIS, and PROSPER, so we should be using an AR [androgen receptor] inhibitor in that setting. My takeaway: don’t get fooled and not give more systemic therapy. Also, reach for something that has level 1 overall survival evidence. That‘s how I took it. I wonder what the medical oncologists think.

Neal Shore, MD, FACS: Bobby, Vivek, what are your thoughts on it?

Bobby Liaw, MD: I’m pretty much 100% in agreement. There are random cases where we get a PSMA PET scan, and we’re surprised that there are multiple spots of disease. That tends not to be the most common situation. Usually, when the PSA [prostate-specific antigen] levels are relatively low, when we don’t see much on a conventional CT bone scan, we’re not expecting to find widely metastatic disease. We’ve had a couple of cases like that, in which case I will absolutely treat those—even those silent on conventional treatment, I will still treat those as metastatic castration-resistant prostate cancer through and through. But for the ones who have a couple of spots of disease, like more low-volume disease, I’ll reach for intensifying their treatment with something that has efficacy in CRPC. Of all the drugs that are effective in nonmetastatic CRPC, like AR [androgen receptor] inhibitors, there’s only 1 approved for CRPC. I might reach for enzalutamide if I was going to reach for an AR inhibitor. But outside that, chemotherapy is an option, and abiraterone is still an option. It will be a game changer once we have more consistent access to PSMA PET scans. It’s going to cause a lot of some stage migration.

Neal Shore, MD, FACS: Great. And last word on it, Vivek?

Vivek K. Narayan, MD, MS: I’ll be brief. Echoing what others are saying, the technology is phenomenal, and we’re going to see that what we’re describing is essentially stage migration or clinical setting migration. But we do need to be a little careful about how that informs the potential treatment and how that may affect our understanding of the biology of the patient’s disease. In terms of intensifying or deintensifying therapies, we need to be a little careful about what this means in terms of the patient’s individual prognosis.

Neal Shore, MD, FACS: Thank you. What great feedback and great pearls and great tips. There’s a lot more we could have talked about. We didn’t have an opportunity to get into genomic profiling—the role for germline and somatic testing. Maybe we’ll come back for another program.

Transcript Edited for Clarity