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Zachary Klaassen: Hi. My name is Zach Klaassen, urological oncologist at the Georgia Cancer Center in Augusta, Georgia. We're on UroToday at ASCO 2025 in Chicago, delighted to be joined, as always, by Dr. Oliver Sartor, who is a medical oncologist in New Orleans. Oliver, thanks for joining us again on UroToday.

Oliver Sartor: Glad to be here.

Zachary Klaassen: So we're discussing a trial in progress, which is really exciting. I think we're starting to see some of these trials and progress moving lutetium potentially up in the disease space. And this is the PSMA delayed castration or PSMA DC trial. Maybe just before we get into the trial, tell our listeners some of the rationale for combining lutetium potentially with SBRT.

Oliver Sartor: Well, let's look at the disease space that we have today. So many patients are going to be treated with radiation or surgery. And unfortunately, there's a lot of recurrences. Some of them could salvage radiation and then go on to have yet another recurrence. And it turns out that oligometastatic disease as detected by PSMA PET scan is very, very prevalent. So what do we do with those patients? Do we put them on ADT? Do we put them on SBRT? Or do we do something experimental? And in this particular case, we're going to do something a little bit experimental.

So let me explain. SBRT, stereotactic body radiation therapy, is now considered to be standard of care for many of these patients who have oligometastatic PSMA PET detected metastatic disease, typically not more than five metastatic lesions, because once you get above that, it gets harder to SBRT them all. But what I'll say is, you can control the disease. But almost inevitably, it comes back. So the question is, how can we keep it from coming back?

And the way that we're going to explore is the SBRT plus or minus PSMA lutetium 177. So the SBRT is going to take care of the lesions. And in order to keep them from coming back in other spots as well, we're going to use the lutetium-- and remember, these are PSMA PET positive patients in the first place-- and try to eliminate the disease that we cannot see and keep it from coming back. If we do that, then our ultimate goal here is to delay castration, delay the time of progression when castration becomes a necessity. Do we know what's going to work? No. Is it worth a shot on goal?

Zachary Klaassen: Sure.

Oliver Sartor: Yes. And if I talk to a man and say, hey, I don't have to castrate you, I don't have to give you hormonal therapy now, what I might be able to do is give you a little SBRT, and then give you an isotope that will delay the time that you need the castration, I think many men would say, sign me up.

Zachary Klaassen: So if I said-- think about this really simplistically. We used to do SBRT, usually with ADT. Maybe we try to delay ADT by itself with SBRT. But we're not replacing ADT with lutetium, but trying to give a different systemic therapy to delay that time to ADT. Is that correct?

Oliver Sartor: Absolutely. So there are men who will be treated with ADT. But we're really questioning the necessity of that. If you use the ADT, then of course, you'll be dropping the testosterone, at least inhibiting the AR axis with something like enzalutamide, an AR antagonist, and elucidating the responses that are characteristic of either castration or blockade of AR. And what happens is that men as a whole would prefer not to do that.

Zachary Klaassen: Yeah, absolutely.

Oliver Sartor: And this is an attempt to be able to delay the need for that. Whether or not we eliminate the need, that's a whole other question. I'm not sure we're that optimistic.

Zachary Klaassen: But delaying is great, though.

Oliver Sartor: Delaying is great. And we have a quantitative endpoint. It's called metastasis-free survival. That means the appearance of new lesions is going to be present on scan that would signify that they've progressed. So the question really is, can we delay the progression by using a systemic therapy with lutetium instead of using ADT? And the answer is, we hope so.

But we don't know.

Zachary Klaassen: Awesome. Tell us a little bit about the trial design intervention schedule, how many patients, and just give our listeners a bit of a breakdown of what to expect from the aspect of delaying castration.

Oliver Sartor: Yeah. So again, to talk about the PSA recurrent population, some of these patients, by the way, will have a really long PSA doubling time and can probably just be watched. So if somebody has a PSA doubling time of 24 months, we just say, leave them alone. You need a PSA doubling time of less than 12 months.

There are also going to be those who just have pelvic recurrences. And we really want metastatic disease because those are the ones that are the most worrisome, so metastatic disease, less than five lesions, PSMA PET, conventional imaging negative. So they've got conventional imaging positive, then the true M1 in the usual sense, and that's a different category of patients today.

So we're going to take this recurrent PSA doubling time less than 12 months, PSMA PET scan positive, conventional imaging negative patient and then say, are you a candidate for SBRT? And if the answer is yes, then that's the first critical point. Then we're going to say, everybody gets SBRT because that's standard of care. Then we're going to have the plus or minus lutetium one-to-one randomization over 400 patients because we need to power it adequately for the MFS endpoint. And then off we go by giving the lutetium for a couple of doses, or there is just observation. There's not an ADT control arm.

And one of the nice things about it, if somebody does have a recurrence, they're eligible for a repeat SBRT, just like it would be in real life. We're trying to real life scenario. So the patients have a recurrence, they have another oligomet, boom. You can zap that. So the question is, are we going to diminish that time to the recurrence in a metastasis-free way that will be construed as a benefit? Of course, we have it all powered out. We have all the trial designs done properly. And we've gone to the FDA on this. So this is not a half-baked theory. We've gone to the FDA. If we have a positive trial, we'll get an FDA approval. And then we'll change practice. So that's the ultimate goal, is always to change practice.

Zachary Klaassen: That's very cool. What's the status of the study at this point?

Oliver Sartor: It's currently accruing. It's open to a number of sites, both in the US and internationally. The trials, patients are being screened, as we speak. And patients will be enrolled, as we speak. It's a little bit too early to talk about the exact sort of timeline for completion. I just can't quite say that yet. And there's some amendments that are coming forward that might change slightly some of the eligibility criteria. But the bottom line is, PSMA PET positive oligometastatic disease with conventional imaging negative, and looking at the time to metastasis, which is really a metastasis-free progression as an endpoint. That's the essence.

Zachary Klaassen: I think, as you mentioned earlier, patients are-- they must be excited about this trial.

Oliver Sartor: Oh, they're very excited.

Zachary Klaassen: This is something that we know ADT free survival is a very relevant endpoint. I'm sure it's one of your secondary endpoints. It's one of those things where we're trying to decrease the burden of side effects downstream. And certainly, this trial is a great jumping off point. We'll definitely have you back on to talk about it as it continues to accrue and certainly when the data is published. So anything else we haven't hit on from PSMA DC?

Oliver Sartor: Those are the highlights, Zach. Thank you for having me.

Zachary Klaassen: Thanks, Oliver. Appreciate it.

Oliver Sartor: Great. Thanks.