Scott Tagawa, MD, on PSMA PET-CT and its Utility in Prostate Cancer - Part 1

In the first part of this two-part interview, Scott Tagawa, MD, MS, FACP, Professor of Medicine and Urology at Weill Cornell Medicine, discusses how PSMA is used in radiographic detection of prostate cancer, the approval of gallium-68 PSMA PET-CT, and how gallium-68 PSMA PET-CT compares to piflufolastat.

He is interviewed by David Ambinder, MD, Urology Resident at New York Medical College/Westchester Medical Center, and Akhil Saji, MD, Urology Resident at New York Medical College/Westchester Medical Center.

Dr. Akhil Saji:

Welcome, everyone. Today, we’re speaking with Dr. Scott Tagawa, who’s a professor of medicine and urology at Weill Cornell Medicine. He’s also an attending physician at New York-Presbyterian/Weill Cornell Medical Center. And today, we’re going to be talking about PSMA PET-CT and its utility in prostate cancer.

Dr. David Ambinder:

We are very excited. We know PSMA has a huge part of the future of advanced prostate cancer. And it’s really cool that you are joining us here, and to hear from you.

Dr. Scott Tagawa:

Sure, happy to be here.

Dr. Saji:

So, Dr. Tagawa, for our first question, can you briefly describe what PSMA is, and then how it’s been utilized clinically in the radiographic detection of prostate cancer?

Dr. Tagawa:

Sure. So, PSMA, or prostate-specific membrane antigen, is a cell surface protein that is present in the normal human body, in the prostate, as well as on the luminal surface in several organs, such as the salivary glands, the lacrimal glands, the brush border of the small intestine, and proximal renal tubules, as well as some ganglial cells. That being said, as a general rule, it is highly over-expressed in prostate cancer, with higher levels of expression generally being associated with increased grade and/or metastasis and AR dysregulation. So, the more advanced disease, generally speaking, there is more PSMA.

That being said, there is PSMA-negative disease, and the biggest hazard for that tends to be the kind of ultimately treatment-resistant type of cancer that some people call neuroendocrine prostate cancer. But when there’s loss of AR, that’s when there’s a higher hazard for PSMA negative. But generally speaking, nine out of 10, there are different ways of saying how often is it, gives me positive or negative. So, it depends on what degree, but would say roughly nine in 10 tends to be positive.

Dr. Saji:

In 2020, I know that gallium-68 PSMA PET-CT was approved for patients with suspected prostate cancer, metastatic disease, or those with rising PSA levels, or basically, in summary, patients that you suspect have recurrence of disease. Do you foresee any other new indications for these scans in the near future?

Dr. Tagawa:

So, there’s indications and some clinical utility that’s just there, and then there’s the FDA. So, you mentioned that the kind of on-label FDA approval for the… There’s two general FDA-approved agents as of May, 2022. There are several different approvals, because one has several different versions approved. But those are the two on-label.

With the approval of a therapeutic called Lutetium PSMA 617, came the companion diagnostic. So, a different version of that same gallium-68 gives me 11. PET tracer became another indication. So, that is for patient selection for that drug, Lutetium PSMA 617, in patients with metastatic castration versus prostate cancer.

So, those are three different on-label uses. I think that there are likely to be a lot more uses, whether it has kind of official FDA approval or not. We’ll see. And I’m not sure how much it matters. So, for those of us that treat advanced disease, we can see responses clinically. That’s quite rewarding, their symptoms, and then patients feel better. That’s great. That’s probably the most important response. You can see PSA go down, and then when they’re soft tissue, we can see traditionally scans shrink, CT or MRI kind of get better.

But we’ve been stuck in bones. A bone scan might look brighter or less bright, and that could be good or bad. It’s tough to say. So, it’s only been a small percentage or proportion that we can look at great graphic response. And I think that is likely to be much higher with PSMA PET. So, the actual ability to look at response I think is something that is there.

I mentioned in your question, what is PSMA? It’s partly related to the AR pathway, so I think we can tell a little bit about the biology of the tumor, what some people call phenotype. So, there’s metastatic disease, kind of ignoring PSA levels, by telling us that there is PSMA to a bright or dim degree tells us something about the biology of the tumor as well.

So, I think there are several different utilities in men with advanced disease. And then getting closer to the initial on-label use is what a lot of people talk about as oligometastatic disease. So, there’s different definitions, but it just means there’s a small number that’s visible.

It’s going to take us a while before we have randomized trials of metastasis-directive therapy, or even systemic therapy, et cetera, with hard clinical endpoints.

But, for those of us that are looking to enroll in clinical trials, or performing what some people call metastasis-directed therapy, I do think that is important to use a sensitive imaging tool in determining whether or not we’re treating most of the disease or not. That might have been not so long ago with a FACBC in PET. Now in that disease state, it’s likely that PSMA PET is much more sensitive. So, if we’re going to go after site disease, I think that’s another indication that we’re learning.

Dr. Saji:

Thank you. Yeah, that’s very exciting. And there’s another scan that you’re, of course, familiar with, Pylarify, or piflufolastat, that was also approved shortly after gallium-68, and with similar indications. Could you talk to us about differences between the two scans and how you used them in your own practice?

Dr. Tagawa:

So, they’re identical to me. So, talking as a physician practitioner, I think they’re identical, basically. So, not talking as a researcher, talking as a clinician, their performance characteristics in terms of sensitivity, specificity, positive and negative predicted value in different disease settings, is virtually identical.

And I think there might be minor differences between the two, but either one of them is so different compared to what we had before. And there are many more questions that I would like to answer versus how big a difference is there between the two, that I would never discourage research, but I’m much more interested in, if we’re looking at other tracers, new tracers with different properties, much more than how good is one compared to the other, taking thousands of patients in one or the other. So, whatever is available, basically.

Hopefully in the not-too-distant future, because there still are some issues in terms of access. That has to do with number of sites that have PSMA PET available, and insurance coverage. But hopefully in the not-too-distant future, it’s pretty wide access, and some places are only going to have one. I think that my advice is, to the doctors and the patients out there, if one’s available, take it.

Watch part two of this interview to learn more about PSMA PET-CT.