Benefits of PSMA-PET for High-Risk/Advanced Prostate Cancer: Part 2

An interview with Russell Szmulewitz, MD, associate professor of medicine and a leader of the clinical and experimental therapeutics program at the Comprehensive Cancer Research Center at the University of Chicago School of Medicine. Interviewed by Daniel Tennenbaum, MD, chief resident at the Maimonides Medical Center urology residency program in Brooklyn, New York.

This is the second part of a two-part conversation with Dr. Szmulewitz. Watch part one of this interview here.

Dr. Tennenbaum:

Have there been any clinical trials comparing PSMA PET/CTs to either standard imaging or other functional imaging? And if so, how has one modality compared to the other?

Dr. Szmulewitz:

So there have been a bunch of studies in various stages of the disease comparing PSMA PET scan to either conventional imaging that I defined earlier or other older PET scans. I would say that the pro PSMA study is probably best done in the localized high-risk setting. A cohort of patients who had conventional imaging and a cohort of patients who had PSMA directed imaging and then before surgery and then went to surgery or were followed longitudinally, and so it allows us to really understand the sensitivity and the specificity. So what we found is that the specificity specifically was better with PSMA imaging compared to conventional imaging, and the sensitivity as well. And so it definitely, from a diagnostic accuracy standpoint, is much better than conventional imaging. It’s just a question of, what does that mean long term in terms of patient outcomes?

And in terms of in the other disease states, there have been a bunch of studies. The initial studies with PSMA PET were all in patients with biochemical recurrent disease in which there were no known spot that you could see at all with conventional imaging, and they were able to detect at PSAs below 0.5 even. At a PSA 0.5 or lower, it’s still about 40, 45% sensitive at detecting a site of recurrence. And so more often than that, it’d still be negative at such a low PSA, but you are picking up things. And it’s also better than an older agent called fluciclovine, two to three times more sensitive depending on the location, lymph node or bone or what have you.

Dr. Tennenbaum:

Understood. Thank you. You had mentioned earlier about therapeutic opportunities using the PSMA PET/CT technology, the PSMA PET technology, I should say. In what way has this been utilized? And is there any hope to use this technology as a way to treat oligometastatic disease to theoretically allow a man who has very few metastatic sites to potentially become NED?

Dr. Szmulewitz:

The first part is how is the PET scans being used in therapeutics? And so theranostics is a field that’s growing in cancer therapy, and that’s linking a therapeutic to an imaging, a diagnostic, and a PET scan in this case. And so recently, FDA approved Lutetium-177–PSMA-617 is a beta emitting lutetium therapeutic that is a ligand that binds PSMA expressing prostate cancer. To be eligible to receive it, you have to have a PSMA PET scan that is positive and you cannot have discordant disease. So as patients become castration resistant and have refractory disease, a percentage of those down regulate PSMA, and there can be some metastases that don’t make PSMA while some do even within the same patient. Either you have to have PSMA positive disease, and you can’t have any discordant lesions, but then it allows access to this novel therapy, which improves survival and shrinks tumors and does many good things from a quality of life perspective.

So this is an amazing new advance for the field. And I think your question about what’s the future of it and where can we go forward is really a critical one. And honestly, I just don’t know. I think there are two large phase three studies moving it forward. There’s a study called PSMA Edition that we and others are participating in that is using PSMA targeted therapy in the frontline metastatic setting and that’s independent of disease burden, meaning high volume, low volume, as long as you’re metastatic and castration sensitive within a few weeks of diagnosis, you can become eligible.

And so that will take it hopefully from a castration resistant late stage post chemotherapy to an early frontline setting. And then the next thing would be perhaps with a shorter course of hormone therapy or not in an oligometastatic setting. I think in that setting right now, we are using SBRT, so focal radiotherapy. And I think what I would love to see is a combination of that and PSMA targeted therapy, because you can imagine that the PSMA targeted systemic therapy might get the smaller ones that just haven’t shown up, yet but we know that are there. So if you can design it, write it and get somebody to fund it, I’m on board.

Dr. Tennenbaum:

That’s exactly what I was thinking about as I asked the question. The theoretical fusing of SBRT with this technology would be wonderful in theory. While we’re on the subject of the future, I often try to ask all the individuals who I speak with in this setting where they see the future headed for our discussion. So do you think there will be any use for PSMA PET/CT in low-risk or intermediate-risk prostate cancer in the future? Or do you think that we’ve reached the finish line for our use or utilization of PSMA PET/CTs?

Dr. Szmulewitz:

Fair question. So I think that we probably haven’t reached the finish line, so there’s other things to be done. I think that there is an association of PSMA PET positivity with higher risk and higher grade disease. So there are studies ongoing to see if, for patients who have low-risk disease and are on surveillance, whether or not PSMA positivity might predict upgrading and upstaging of disease over time.

The sensitivity isn’t good enough to replace other modalities or surgery, meaning that a negative PSMA PET scan, even if you’re intermediate risk, doesn’t mean that you have no risk of occult metastases or things of that nature. I think that it will be another test that we can do in conjunction with MRIs and in conjunction with… What I think it probably will replace is conventional cross-sectional imaging and bone scans, in terms of the staging, because I think it is more accurate in that way. But I just don’t know what the long term ramifications are for changing therapy decision making, based on these.

Dr. Tennenbaum:

Understood. Dr. Szmulewitz, thank you so much for your time. This was an insightful discussion and we really appreciated you taking the time out of your very busy day.

Dr. Szmulewitz:

Great, great. Have a great day. Thank you.

Dr. Tennenbaum:

Thank you, Dr. Szmulewitz. Thank you so much.