Targeting PSMA in Advanced Prostate Cancer - Episode 7

The Clinical Utility of PSMA in Advanced Prostate Cancer

April 20, 2021
Ulka Vaishampayan, MD

,
Oliver Sartor, MD

Key opinion leaders expand on the broad clinical utility of prostate-specific membrane antigen (PSMA) for patients with advanced prostate cancer.

Ulka N. Vaishampayan, MBBS: What is PSMA [prostate-specific membrane antigen], and how can a PSMA PET [positron emission tomography] or CT identify phenotypic biomarkers? Do you want to comment on this? 

Oliver Sartor, MD: Sure. Let’s talk about what PSMA physically is. It’s a transmembrane protein. By the way, it is interesting that the target of PSMA has been in the clinic for a long time. There was a molecule called ProstaScint that targeted an internal epitope of the PSMA molecule. Then we used it for imaging, and it wasn’t very good, but it was better than anything else we had. It was the first molecular imaging in prostate cancer.

We have evolved much further. PSMA is actually a folate hydrolase. It’s transmembranous. The majority of the molecule is on the extracellular side and only at minimal amount on the intracellular side. The wonderful thing about PSMA is that we’ve learned how to image it well. We were initially working with some antibodies, which are not optimal in these agents, and then discovered small molecules that would bind tightly to the folate hydrolase and then could be tagged with things like the F-18 [fluoroethyltyrsine] or gallium-68 to be able to use PET imaging. That’s where the precision really occurred.

In my opinion, this approach is about to transform prostate cancer because of the tremendous number of patients who can benefit from PSMA imaging, both in the early stage disease pretherapy and in the recurrent setting. There are also some predictive biomarkers. 

This is a big area. We’re going to find out a lot more about PSMA over the next decade, but I’m anticipating PSMA PET to be FDA approved for the gallium-68 and the F-18–based molecules later this year.

Ulka N. Vaishampayan, MBBS: It also has the advantage that imaging is noninvasive. It’s fairly easy to do for the patients. You get a very rapid turnaround time for the readings, compared with sending genomic markers that you have to wait a long time for. If the patients need a biopsy, there is the invasive nature of the biopsy, which is sometimes another hurdle for some patients. 

The proPSMA studies showed us that, compared with conventional CT bone scan imaging, which we knew was extremely limited utility, especially in patients with low PSA in prostate cancer, PSMA PET scan remarkably improved sensitivity and specificity of detection of the cancer. Of course, at lower and lower PSA levels, you can still be able to detect oligometastatic disease. 

Oliver Sartor, MD: It’s interesting and a bit of a sea change that we’re about to see, hopefully not only in the diagnostics but in the therapeutics. The therapeutics are what have people very excited because we hope the opportunity to treat PSMA-positive prostate cancer is around the corner. We already have some preliminary data that is quite provocative.

Ulka N. Vaishampayan, MBBS: That’s right.

This transcript has been edited for clarity.