Zachary Klaassen: Hello, UroToday. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm pleased to be joined with Dr. Antony Pellegrino, who is a urology resident at San Raffaele in Milan, as well as a clinical research fellow at Memorial Sloan Kettering in New York. Antony, thanks so much for joining us on UroToday.

Antony Pellegrino: Oh, thank you for having me.

Zachary Klaassen: So we're discussing some work you presented at AUA, and it's really interesting. It's looking at the impact of PSMA-PET in the setting of salvage radiotherapy versus conventional imaging. And so we know we're a couple years out from the EMPIRE-1 study that was published that showed improved outcomes with fluciclovine PET versus conventional imaging in the same setting. So maybe just set up the background for your study why you guys looked at this in your cohort.

Antony Pellegrino: Yeah, so sure. This study was presented at the AUA by my colleague and friend, Pietro Scilipoti. So what we essentially wanted to do was to look at the update on how practice has changed in the past 5 to 10 years and how the impact of imaging has changed how we treat our patients and what the outcomes are.

And so we essentially took patients which were staged using a negative PET-PSMA and also compared that to patients which were staged with the conventional imaging and were negative. So of course, one would think that we have different patient populations, which is true. And we use a propensity score matching to try to balance out the differences, the clinical differences.

Zachary Klaassen: Excellent. And I know you have some slides that will walk us through the design and the results. Why don't you share those with our listeners.

Antony Pellegrino: OK. And so as I said, that we looked at the patients which had developed biochemical recurrence after radical prostatectomy and were considering therapy. So these are all patients with which according to the AUA guidelines, we actually want to do something on. And by looking at these patients, we managed to assess which patients and how it differed between patients which were assessed using conventional versus PSMA-PET.

And we took the negative of both imaging modalities and assessed outcomes, in our case metastasis-free survival. We assessed clinical recurrence. And to do that, we looked at 601 patients which we had staged in the past 10 years, according to PSMA-PET. And we had a large database of patients assessed with conventional imaging. And we then matched out the clinical differences using a propensity score matching model. And we looked at year, age, PSA doubling time, Gleason score, and other pathological stages to really neat out and single out the benefits that the imaging modalities have given us across the years.

And then we looked at the impact of these outcomes on metastasis-free survival. And on the left, it just shows that after propensity score matching, the variables were similar. And on the right, we can see that the two-year cumulative risk of metastasis was doubled for patients which were staged using conventional imaging. And essentially, that's what we looked at.

And what our conclusion and take home message was that, essentially, that patients assessed with a novel modality, they have a different approach to treatment. They receive a different approach to treatment, and whether that be through more actionable disease states. So get a more complete treatment, more comprehensive treatment.

But also, there's this new emerging role of metastasis-directed therapy, which are these spots that may have come up in PSMA, which probably wouldn't show up in conventional imaging. And all this has shaped practice along the years and has translated in-- I'll go back-- has translated in this large benefit. Because if we look at this, this is only two years difference and we're already seeing quite a large difference.

Zachary Klaassen: Yeah, absolutely. I mean, this is really interesting data. And I think when we look at the landscape of prostate cancer, we talk about stage migration and whatnot. And I think what-- I'm an optimist. I think if we change treatment early, we'll see downstream outcomes be meaningful if we get it right the first time. Obviously, it's going to take a few years to get that. But you guys have shown very, very interestingly, at two years already, MFS is improved with appropriate staging. So what are your thoughts when we look at downstream overall survival? Do you anticipate that a better selection up front will lead to better downstream outcomes?

Antony Pellegrino: Yeah. Because I think this is how the landscape of post prostatectomy patient selection is panning out. So now we have the risk scores, risk classification for patients which develop BCR. In theory, patients with a low risk can be observed. And so we are modulating and trying to dissect out patients which will really obtain a benefit from treatment. And there's another point also to consider that which is often overlooked and which is the competing causes of mortality. So we're looking at metastasis here. And overall survival is an important outcome.

However, we must also look at prostate cancer-specific mortality. And I feel that we're heading towards the right direction. Also because initially, metastasis-directed therapy when it was included, the first outcome which people were interested in was ADT-free survival. So can we push back patients which are going to be taking ADT. Now I think that we're looking at can we make a comprehensive treatment package with optimal staging, salvage-radiotherapy, hormone therapy, and just follow them up. So yeah, I absolutely agree with your point.

Zachary Klaassen: Yeah, that's well said. I think your point about competing risk is important. We know these patients all probably have cardiac risk factors. Does what we do affect prostate cancer-specific survival? I think it's a great point. Overall survival for sure. But maybe more in this context, prostate cancer-specific. I want to touch on one more point. I think when we look back a year, it's already been a year since Todd Morgan presented the Salvage AUA guidelines and really recommending PET scan at about a PSA of before salvage therapy. So whether that's 0.15 for early salvage or 0.2, 0.3.

I tell my trainees if the PET's negative, still give them salvage to the bed of the prostate, or it used to be. But what are you guys thinking. Is that similar in Milan? Are you guys doing that PET scan early to see where they're at and then taking it from there with PSA?

Antony Pellegrino: Religiously. So yes. So essentially, that's a really good point because it's on the baseline, on the face of it. The imaging modality hasn't changed how the guidelines are written. So essentially, if it's negative, whether it's conventional or PSMA-PET, you should always irradiate the prostate bed. And that is a really good point, which sometimes I do think gets missed.

Zachary Klaassen: Sure.

Antony Pellegrino: So it's not a case of, OK, we can follow it up and see where it goes. Even though that is the case for what we're including now in the guidelines for the AUA low risk group. So that may be the case, but I think that's something that should be weighed upon earlier before one does the imaging modality. It shouldn't be just actionable just because you can't see anything and you don't do anything. So that's a really good point.

Zachary Klaassen: Yeah. I mean, we have great trials from historic previously to PSMA-PET but early salvage works. But I think the take home from, I think, your study, correct me if I'm wrong, is fine-- if there's something else outside of that box, what do we do with that? Treat them with MDT, ADT, like you said so. Great discussion. Any take-home messages for our listeners before we wrap things up?

Antony Pellegrino: Adopt PSMA-PET. And--

Zachary Klaassen: Yes, in general.

Antony Pellegrino: --I'll adopt one of your comments that if negative, irradiate if actionable.

Zachary Klaassen: Yeah, it's great work and very well presented. Congratulations on the presentation. And as always, thanks very much for joining us on UroToday.

Antony Pellegrino: Thank you very much. Thank you for having me.