Neal Shore, MD, FACS: You’re making me think of a lot of questions. But before we go back to how you pick treatment based on conventional imaging, a fluciclovine [Axumin] scan, or a gallium 68 PSMA [prostate-specific membrane antigen] scan, I wanted to ask you, William, to review for us these 3 key clinical trials that have really changed the approved labeled indications for these drugs.

William Oh, MD: As a reminder, this is an artificial disease state. We created this by treating patients who had a biochemical relapse with no evidence of metastatic disease with ADT [androgen deprivation therapy]. Almost all of them respond, and then they relapse years later, and that’s the disease state we’re talking about: M0 or nonmetastatic CRPC [castration-resistant prostate cancer]. When we use conventional imaging, as Alicia Morgans pointed out, we often can’t see it. As Pedro Barata pointed out, some of these newer imaging tests—such as in a very interesting study with PSMA scans—pick up on some metastatic disease in almost all these patients. This disease state not only is shrinking but may go away in the future.

But it’s here now. We all take care of these patients. Three studies were designed to look at the use of next-generation AR [androgen receptor]—targeted therapies in this setting: SPARTAN, PROSPER, and ARAMIS. They each looked at 1 of 3 of these next-generation drugs: enzalutamide, apalutamide, and darolutamide, most recently. They were all very positive clinical trials. They all showed a significant delay in a novel end point that the FDA accepted, which was metastases-free survival, or MFS. I was a little surprised that they accepted that because it’s not the same type of end point we’re used to seeing the FDA accept. But in truth, we know this is probably a clinically meaningful end point in that we know when physical metastases on conventional imaging can be seen—as opposed to fluciclovine or a PSMA—those patients can develop symptomatic disease within a short period of time.

MFS was the end point, the patients were selected based on a PSA [prostate-specific antigen] doubling time of less than 10 months, and there was up to a 2-year delay in MFS in all 3 of these studies. They were actually very similarly designed, and the outcomes were quite similar between the three trials. We’ll talk about some of the nuances in a minute, but on that basis, all 3 of those drugs are approved.

Neal Shore, MD, FACS: That’s a really good summary. Getting back to the imaging, you’re right: everything was done just as all our phase III trials are done, based upon PCWG [Prostate Cancer Working Group] criteria, using conventional imaging. Now we’re using these novel or next-generation imaging methods. Nancy, are you using fluciclovine scanning regularly? Are you using gallium 68 PSMA imaging? Indeed, when gallium 68 PSMA imaging becomes available, we’re hearing that there may be an NDA [new drug application] available. By the end of the summer we may, in the United States, have ubiquitous access to gallium 68 PSMA imaging. We’re behind the rest of the world, where it’s been around for a long period of time.

Nancy Ann Dawson, MD: I have to admit, I use a lot of conventional scanning. I always have to try to figure out, why am I doing more scanning? It depends on what I’m looking for and why I’m looking for it. If I do a technetium bone scan, a CT [computed tomography] scan of the abdomen and pelvis, and a chest x-ray, and I find disease, then I don’t know that I’m particularly motivated to see if I can find more. The patient is already upset. They’ve been told they have metastatic disease and they have 3 or 5 lesions. I don’t need to tell them they have really 50 lesions. In that setting, if I’ve got a positive scan, I’m not going to go off and perform all these extra scans.

The patients I tend to use more of the Axumin scans in are the patients I don’t find metastases in. As you said, it depends on where you work. If I don’t find anything and I perform an Axumin scan and I see a small lymph node up in their supraclavicular area, my radiation oncologist might just want to radiate that oligometastatic disease if the patient does not want to go on hormonal therapy. That’s a patient who would get an Axumin scan. I do perform some. Mostly, I’m looking for disease that I didn’t already find because I’m planning to do something about it.

I’m lucky that in my area—I’m in Washington, DC—the NIH [National Institutes of Health] has been doing a lot of PSMA scanning, so I’ve been sending patients to them on a regular basis. We’re involved in a trial known as ARROW, so we’re doing PSMA scanning as part of that study. Probably like everyone else on the panel, I’ve had people travel all over the world to get their anti-PSMA therapy and their PSMA scan. But they have to fit the category. The NIH has a certain PSA that you have to have to qualify for their PSMA study. I don’t always do all this extra scanning. I will make the comment, though, that if you have a patient, and you’re planning to take out their prostate, the data showing all the occult disease that’s picked up on PSMA scanning would be pretty important to know.

Neal Shore, MD, FACS: We’re heading into an interesting area, and different working groups are starting to really weigh in on this now and trying to come up with further consensus panels. This question was heatedly discussed at Basel, Switzerland, during the Advanced Prostate Cancer Consensus Conference. I would encourage folks to look at the findings and the discussion and how the votes came out during that. It was just recently published in European Urology.

Transcript Edited for Clarity