Experts explore PSMA's significance in prostate cancer imaging, covering its expression, limitations, and transformative role in detecting even low PSA recurrences with PSMA-PET technology.
di Abdar Esfahani, MD, MPH: Dr Kella, please provide us with a little bit of background information on PSMA. What is PSMA, and how would it express? Where would it express? And [is there] any specific information that we need to know as a large community in terms of the PSMA PET [scan] and its limitation and its power?
Naveen Kella, MD: Sure. Thanks, Dr Esfahani. PSMA is a transmembrane protein. It’s found in the prostate. [The acronym stands for] prostate-specific membrane antigen, however, it’s really not specific. It’s actually found across different tissues, secretory tissues. Imagine the salivary glands…kidneys, bladder, liver. Those are all areas where you could have some expression on the scans where you’re interpreting and you see activity. Now, fortunately, it’s highly expressed: 100 to 1000 times more expression of PSMA on prostate cancer cells. Not all of them, but up to 90% or 95% of prostate cancers will have PSMA expression. And what’s interesting is that as the cancers become higher grade, the PSMA tends to be expressed even more. As you get further along, perhaps post chemotherapy or for patients who start to have small cell prostate cancer, those types of prostate [cancers] are not going to make PSMA. So it’s not a perfect test [but] it’s a really good test. And it comes in nicely with PET/CT….
From a urologist’s perspective, I’ve heard about PET/CT for so many years, but we never really used it. It didn’t have much utility in the prostate cancer space. One of the first tests was the sodium fluoride testing, and I never ordered it, but I’d read about it and knew that it was good for picking up lesions just on the bone. And it had a lot of false positives. But then other things came out. I started having patients asking me about choline, and I was not sure even where [I could] get this test. It turned out you could only get it at 1 institution, at Mayo [Clinic], and maybe a few other places. So really, we didn’t use anything until 2016 when fluciclovine came onto the market, and that was a test that I was getting [and] I was using more and more. It was superior in my eyes for picking up prostate cancers, for example, recurrences at small PSAs, and it was a test that was pretty widely available.
But then in 2020 and 2021, we were introduced to PSMA PET/CT with gallium and with fluorine. And these tests actually were compared head to head in a study against fluciclovine. [It was] a really good study where patients were [randomly assigned] to get one or the other and [it] was twice as likely you would … have findings with the PSMA studies compared with fluciclovine. And that was across different parts of the body. One area that maybe was the same was at the prostate bed, but it was barely superior for fluciclovine compared with PSMA. And then the other thing is that it became very widely available. Thousands of places now offer the tracers. For urologists, it’s a tool that’s now available to all of us and patients who are indicated. As far as how does this affect things compared with conventional imaging? One of the things that we found is that for patients with very low PSAs after a recurrence of prostate cancer from surgery or radiation, the PSMA can pick up disease at extremely small PSAs, from 0.5 to 1. Seems like the sensitivity is 50% to 60% with both of the tracers. So that’s extremely valuable to us. And these types of things … they’re calling next-generation imaging, but now it seems like it should be current-day imaging.
Transcript is AI-generated and edited for clarity and readability.