Phillip Koo:

Let’s get right to it. We're going to start off with PRIMARY2.

Zachary Klaassen:

Yes.

So, PRIMARY2, this was presented at the European Association of Urology. That's one of our, probably, two biggest, urology events, the other one being the American Association of Urology, which will be later this May. So, EAU was in London in, earlier this month.

And PRIMARY2 is a really interesting study. So this is men that were from Australia, 7 Australian hospitals. They had an MRI previously that had a PI-RADS 2 or PI-RADS 3 lesion, and this is sort of the less aggressive-looking lesions on MRI.

And then they were randomized to the control, which is standard of care, systematic transperineal biopsy versus PSMA PET scan, and PSMA PET's typically been for biochemical recurrence, staging high-risk patients. So this is moving it up to the pre-diagnosis stage. And then the patients had a positive PSMA PET scan, then it went a targeted biopsy in that area.

If it was negative, they had no biopsy. So, the way we look at this is sort of trying to really identify those patients that maybe didn't have aggressive features of it on MRI, but maybe on PSMA PET scan, there's something there. So, if you look at… there's two sort of ways to look at this.

Can we diagnose clinically significant prostate cancer, and can we avoid biopsies in men that don't need a biopsy? And so, if you look at the right side of the screen, biopsy avoidance, 49% of patients were able to avoid a biopsy, and they'll continue to follow these patients for many years to sort of see if these results are truly safe.

And the other two outcomes were significant prostate cancer. We want to make sure, if we're avoiding biopsies, we're not missing clinically significant prostate cancer. And we saw that the patients that had a PSMA PET versus those that didn't.

There was a non-inferior difference… there was a non-inferior margin that was met, which means that there was no clinically significant difference in the rate of significant prostate cancer. That tells us that PSMA PET will hit that cancer, but it's not going to miss the really bad ones.

Insignificant prostate cancer is always a bit of a conundrum, so this is… it sounds like a bit of a misnomer, but this is the low-grade, low-volume prostate cancer, likely to be non-life-threatening, but we have to deal with them when we find them, and so we want to try to avoid finding insignificant prostate cancer, and we found that PSMA PET was able to decrease the risk, or the rate of… insignificant prostate cancer.

So, we're avoiding biopsies, hopefully appropriately, we're not missing clinically significant prostate cancer, and we're avoiding the diagnosis of insignificant prostate cancer with this trial. So, very important trial as we see where we can utilize PSMA PET, perhaps other places than we traditionally have over the last 5 or 6 years, and so kudos to the Australian folks who put this together.

And this study was funded by PCF. Which is really important, and we can sort of see, real money being turned into research that hopefully can benefit patients.

 Phillip Koo, MD

Zach, this is really awesome. All of our listeners know about PSMA PET. It's become such an important part of how you stage prostate cancer at initial diagnosis, at biochemical recurrence. It's also used to treat and find patients who should undergo Pluvicto-type therapies. This is the first time we now have this pretty convincing data about using it in diagnosis in the prostate itself. So tell us a little bit about how you foresee this being incorporated into clinical practice.

Zachary Klaassen:

Yeah, it's still early. I mean, this is a big study. I think we, you know, Australia's done, or the last 20 years, has really been at the forefront of PSMA trials, and they continue to lead with this trial. Is it ready for prime time tomorrow? I think… probably not. I think there's gonna be additional, probably, validation following these patients a little bit longer.

But we're certainly seeing… again, you don't want to miss significant prostate cancer, and you don't want to over diagnose insignificant prostate cancer, and hit both of those metrics. So I think this has promise. Is it ready to be in the clinic tomorrow? Has to go through approvals, has to go through regulatory.

And certainly, the insurance companies have to pick up on this. And so, I'm hopeful all this gets approved. It's going to be in the hands of the clinicians. Again, this is PI-RADS 2s and 3s. This is not for the 4s and 5s that we know there's likely prostate cancer there. Patients should get a biopsy. And then if they have high-risk disease, then they certainly qualify for a PSMA PET scan after that, so…

I hope it gets approved, we'll have to use it judiciously, have to make sure it goes through the appropriate steps to get there. But, good quality data and a good trial like this certainly piques our interest, and hopefully we'll see it come down the pipeline.