Scott Tagawa, MD, on PSMA PET-CT and its Utility in Prostate Cancer - Part 2

In part two of this exclusive interview, Scott Tagawa, MD, MS, FACP, discusses clinical trials he’s watching for, using PSMA for an initial prostate cancer diagnosis, and the predictive values of PSMA.

Dr. Tagawa is a Professor of Medicine and Urology at Weill Cornell Medicine and attending physician at New York-Presbyterian/Weill Cornell Medical Center. The interview is conducted 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. David Ambinder:

Going out of the clinician world and into the research world, anything exciting to you, clinical trial wise, that you’re watching in terms of what we could see in the future?

Dr. Scott Tagawa:

So, let me speak broadly first. So, it’s kind of the same topic that we talked about before with the utility, or what are the different areas besides initial staging or biochemical recurrence for PSMA PET. I think that we may be able to look at response, like other diseases have been able to look at, and maybe can get faster drug development.

So, that’s something just generically that I’m looking forward to, whether it’s another AR targeted drug, novel AR targeted drug, a novel chemo, novel immunotherapy, et cetera, because PSMA is something that is there on most prostate cancer cells, and if there’s less that is are there, having nothing to do with specific PSMA expression, just a lower volume disease, I think we can see that.

And that’s beyond PSA. It’s incumbent on us through the trial list to insert those in multiple clinical trials. And there’s a cost that’s associated with it. Hopefully we can get that out there, prostate cancer working group four is in progress, and hopefully we can get that out there and have it built in the clinical trials, and that’s the future method. There’s never a place for CT-MRI bone scan, but hopefully it’s going to replace that a lot. So, anyway, that’s one area specific for imaging.

Dr. Ambinder:

It really is exciting times in that regard.

Dr. Tagawa:

And then there’s, as a target, as a therapeutic target, we have one drug approval. I think that there is room for more. There are five phase-three trials of which I’m aware, and number of other phase-twos and phase-ones that are there. Those are just for the radio label agents. Actually, even more specific, that’s just for Lutetium 177.

So, there are other betas that are out there. There are alphas that are now in the clinic, and there’s Augers that hopefully will come. And then beyond radioactive particle, radionuclide therapy, we can use it as a self-service target for drugs, such as antibiotic conjugates, for immune systems, or whether it’s biospecifics, or CAR-T cells, I think that it can exploit the somewhat selectivity of PSMA and use it for a lot of different therapeutics.

Dr. Ambinder:

It can really open a lot of doors. And a lot of what we talked about are advanced prostate cancer and utility of PSMA or PSMA imaging during advanced prostate cancer. Is there anything that you are thinking of using this, let’s say, at an initial prostate cancer diagnosis, maybe in the local setting?

Dr. Tagawa:

Absolutely. I’ve used the term clinical localized forever, because something that’s high risk, classically high PSA, Gleason group five, positive DRE, et cetera, we call that high risk. Not because it can’t be cured with a knife surgically, it’s a lower chance. So, is there a cell that’s outside the prostate, right?

So, now that we have a higher sensitivity detection tool, we can see that. This exact same patient, all of a sudden, we see extra prostatic disease, doesn’t mean that that person would not benefit from local therapy. But more clearly in my mind needs something that is a little bit more.

So, just with the existing therapeutic tools, hormonal agents plus surgery plus radiation, et cetera, that is something that is today, really. And then, I think for the future, it may be more potent what we have. So, for metastatic disease, we’re now using triplet therapy for some patients, and that triple therapy is way more effective, in that castration sensitive, hormone, sensitive, non-castrate setting, those are all synonyms, than it is for CRPC.

So years, rather than months, moving in earlier, are we going to see cures in combination with surgery and radiation? Maybe, and this will help us determine that. And then using, if we can see it some of the time, maybe we can treat it some of the time effectively.

So, I don’t think that Lutetium or a beta is necessarily the best therapeutic tool that we have for micrometastatic disease, maybe low volume mets, but not truly micrometastatic, but some of these other drugs or immune therapy or alpha, or Auger emitters, maybe. So, that quote “high risk” that we can see, we can do something now. That quote “high risk” that we can’t see, so PSMA PET’s not perfect, it’s going to miss some disease. Actually, when we look at microscopic lymph node disease, it’s 40%, i.e. 60% we miss.

That tells us there’s something that’s out there. So, I think that hopefully in the not-too-distant future, it’s not going to be next year, but sometime down the line, maybe those that walk in the door with a PSA of 20, Gleason group five, palpable disease, we can cure them, not just with the knife only, but in combination with some additional therapy.

Dr. Ambinder:

What is the sensitivity and specificity and the predictive values of PSMA?

Dr. Tagawa:

So, it depends on the setting. So, I gave you that 40%.

There’s not huge numbers of patients that have pathologically proven lymph node disease, just because it’s not the vast majority of patients that we see out there. So, there are patients that walk in the door with high-risk disease, and we see mets. So, that’s going to be a little different. We’re doing studies like SWOG 1802, looking at what’s the utility of prostatectomy with metastatic disease.

But ignoring that, the available data is that sweet spot for negative systemic mets, but then go to prostatectomy and have lymph node positivity. So, anyway, the numbers are not so large. But interestingly, the two large trials that led to the approval of the two agents, PSMA 11 and DCFPyL, showed the exact same results in this setting, where about 40% of that microscopic lymph node, pelvic lymph node disease that was seen at lymph node section, was imaged, and that much higher than is seen with any other imaging modality.

But it also points out that a PET scan, even with a highly selective cell surface target, is not the same as a microscope that can pick up single cells.

So, it’s a major improvement, but it’s not quite there. To pick up everything, I think that there’s an interesting data that really first came from Europe, and now it’s coming in the United States, and this is, I think, most helpful when there’s a high suspicion, or even a positive PET. The UCSF data pointed out, UCSF/UCLA combined, pointed out some of the positive PSMA PETs were called negative lymph node dissection, or a false positive, were really probably true positive, just missed that resection or biopsy.

So, the combination of PET imaging with probes, intraoperative probes, increased the yields, particularly now we’re seeing these lymph nodes that I would call weird place, at least weird traditionally, perirectal, and things that we wouldn’t have seen before.

Dr. Ambinder:

Sure. Yeah. I mean, I think what we learned talking with you, this is a start. We’re moving towards very exciting things. We’re not quite there yet, but this is another very interesting thing I think every urologist needs to be following and needs to be involved with. It’s been really awesome talking with you and getting your perspective.

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