GU Oncology Now spoke with Thomas Hope, MD, Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco, to gain expert insight on the clinical benefits of using PSMA imaging for the staging and management of prostate cancer.

GU Oncology Now: What are the clinical benefits of PSMA PET for the diagnosis and management of prostate cancer?

Dr. Thomas Hope: Yeah, so PSMA PET can definitely help out in terms of managing patients with prostate cancer. It really depends on the stage of the cancer of how it will impact that decision-making. So with the approval of the two PSMA PET radiotracers out there, PSMA-11 and DCFPyL, they’re both indicated at an initial staging in a time of biochemical recurrence after definitive therapy. At initial staging, really what you’re looking for is the presence of metastatic disease. Disease that you didn’t know about in order to make sure you don’t treat someone for localized disease when they in fact have disease beyond the prostate. To make sure that you choose the appropriate therapy for that patient.

At a time of biochemical recurrence, it’s similar but slightly different. In that setting, you’ve already done your definitive therapy. You’ve done a prostatectomy or radiation therapy. They’ve removed the prostate and now the PSA is rising. And now at that time you want to know where the disease is so you can localize it and potentially treat it with external beam radiation therapy. So the idea there is trying to localize known recurrences. Is it still in the prostate bed? Is it metastatic in the bone or the nodes? And by being able to tell where the disease actually is, you can then potentially really dramatically improve patient outcomes by hopefully doing some definitive therapy to those sites, oligometastatic disease.

Can you articulate the clinical implications supporting the timely diagnosis of prostate cancer?

So I think that is yet to be demonstrated fully in prospective trials. The idea here again is to localize where a disease is so that surgeons, medical oncologists, and radiation oncologists can treat the patients appropriately. What we don’t really fully understand is how that will improve patient outcomes. Recently, there was a very well done trial out of the University of Emory called EMPIRE-1 and EMPIRE-1, in essence, randomized those patients with biochemical recurrence to receive either a Fluciclovine PET or conventional imaging. And in that trial, they demonstrated there was a marked improvement in biochemical-free survival four years after randomization demonstrating that if you target oligometastatic disease with external beam radiation therapy, you can really prevent recurrence over time.

Now, similar trials were being done with PSMA PET, which will presumably be better and have more improvement in patient outcome with a longer biochemical-free survival benefit. But those trials have not yet reported out. I think the one that will be soonest will be the UCLA trial doing PSMA-11 PET compared to conventional imaging. But the goal here really is to if you appropriately treat the disease by knowing where it is, you can prevent the need for systemic therapy in these patients and give them a longer period of time off of androgen deprivation therapy or other systemic therapies.

When should physicians implement PSMA PET in their practices to improve outcomes in patient management?

So when should you use PSMA PET? So I think the first aspect of that is availability, which is right now for the next couple of months, an issue. Gallium PSMA-11 was approved at just UCSF and UCLA. Soon, hopefully in the next few months, a kit will become available where more sites will be able to use it. DCFPyL was approved in May of this year. And so that drug is taking a little time to get the insurance authorization contracts and manufacturing up and running. So hopefully maybe near the September timeframe, most sites in the U.S. might have access to it. There’s only a few areas in the country right now that are able to get access to DCFPyL. So the first is just getting access to the drug.

The second is in which patients do you want to use them in? So again, the FDA approved both of the drugs in the same indications in the initial staging and a biochemical recurrence. In initial staging, you obviously want to use the drug in patients who are at risk for metastatic disease, so you don’t want to image patients with a low risk prostate cancer. My guess is that guidelines will start to incorporate PSMA PET in unfavorable, intermediate risk, and high risk prostate cancer patients at initial staging and biochemical recurrence. It gets to be a little complicated. People frequently ask, “What is the trigger PSA? What PSA should I wait for a patient to get to before I get a PSMA PET?” And in my mind, there’s no right trigger PSA because it really depends on the individual patient and what you’re planning to do. If you’re planning on doing salvage radiotherapy after radical prostatectomy in a patient has a PSA of 0.1, and you’re going to do treatment anyways, the 20 to 30% chance that you see disease on a PSMA PET will actually dramatically impact that patient’s management, even if it’s unlikely to be seen.

So it really depends on the clinician, the radiation oncologist, and the patient as to when you would choose to do that. But generally in the biochemical recurrence setting, it’s much better than Fluciclovine, bone scanner or CT and so should just replace those imaging studies in that setting. And then the last area, which is really about to come, but isn’t here yet, is in the area of theranostics. So most people have heard of the VISION trial. The VISION trial read out at ASCO this year and showed a benefit in overall survival and treating patients with Lutetium 177 PSMA 617. And you’re going to need to use a PSMA PET in a castration resistant population to demonstrate that the targets there, that patients are PSMA avid are good candidates for therapy. But that probably won’t really be a big deal until FDA approval of that drug probably by the end of this year.