Zachary Klaassen: Hi. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We're at AUA 2025 in Las Vegas. I'm delighted to be joined on UroToday by Dr. David Morris, who is at Urology Associates in Nashville, Tennessee. David, thanks so much for joining us on UroToday.

David Morris: Thank you for having me.

Zachary Klaassen: So we're going to talk about a really interesting subgroup analysis of TRITON3, looking at specifically patients with liver metastasis. We know these patients historically do not do very well. We're going to get into that. But maybe just by way of background, just tell us about the trial design for TRITON3 and maybe what the initial ITT results showed.

David Morris: Sure. TRITON3, first published a few years ago now, originally for men progressing on an AR agent who had CRPC disease and had BRCA1, 2, or ATM mutations. It's actually a very interesting trial design because the control arm was a physician choice that included a little over half patients getting docetaxel versus half getting an AR switch.

And so the 2-to-1 randomization-- people getting Rubraca versus the physician choice-- there was improvement in PFS. It was almost double the amount of time PFS. And now the AR switch is known to not be a great control arm in that situation. But this is the first head-to-head data showing that for BRCA patients specifically that using a PARP therapy is actually better than using docetaxel. So mostly, that informs our decision on sequencing for men with BRCA mutations.

Zachary Klaassen: Yeah, great summary. And I think before we get into this data, just tell us about what liver metastasis means to these patients and what historically it meant.

David Morris: So liver and any visceral disease, but liver specifically has historically just been a really bad prognostic sign. Liver patients do worse than patients with bony and nodal mets. And really, this subanalysis of this data set just shows how poorly liver patients do. And I think the options have been somewhat limited once we get to visceral disease. They're really it's a smaller subset of almost all the trials.

So even if you look at NCCN, for example, there's not a lot of great category 1, this is the therapy to use for visceral disease. We've had options, including chemotherapy and AR agents. But for this patient population, who's already progressed on an AR agent, it's been fairly limited. And the success has been unfortunately bad. It usually is a sign of translation of the cancer from being adenocarcinoma that's AR-sensitive into more neuroendocrine small-cell strange mutational drivers.

Zachary Klaassen: Yeah, absolutely. Just tell us about just the study design for this analysis and maybe some of the key findings that you presented at AUA.

David Morris: So this subset was really pulling out of that TRITON group, those who had visceral liver Mets at baseline. And the same randomization would have been placed. It was stratified for that. I think the real takeaway from the poster and from this analysis is that liver patients live about half as long as the intent-to-treat population. So it's really a call to action for anyone who has a liver met noted on imaging.

The clock started probably last month. It's time to get moving. It's time to consider biopsies, next line of therapy. Don't take time to try to make a decision. And it really calls to the decision of having early testing, germline and somatic, to identify patients who would be candidates for PARP inhibitor because if you wait and test after the mets developed, it may delay the next line of therapy.

Zachary Klaassen: Yeah, great summary. I think just from just how we look at from a high-level view, you get a patient with liver metastases now. Rucaparib maybe is an option. Clinical trials is an option. How are you counseling these patients about next steps at that time of liver metastasis?

David Morris: So liver mets is nice now to have some additional data saying, in the BRCA-mutated patient population this might be an option to look at PARP-directed therapy-- Docetaxel-based chemotherapy, lutetium, which is now approved in a pre-chemo setting, and there's been mixed data, both for chemotherapy and for lutetium in terms of liver met patients.

There have been several analyses of the cohort groups out of the Mayo Clinic ran these are our patients with liver mets. And some certainly respond. Some don't. But it's nice to at least have options available for them. And none of them are really clearly the winner and the best for each liver patient, so it's really a patient discussion about their risks, their tolerance for other things.

Zachary Klaassen: Yeah, absolutely. And always clinical trials if they're available too.

David Morris: Oh, for sure. I mean, that's the only reason we have these medications to use is because patients have been willing to say, I think this trial design makes sense, and I'm ready to proceed.

Zachary Klaassen: Awesome. Great discussion. Maybe just a couple take-home messages for our listeners.

David Morris: I think it's a call to action for patients with metastatic disease need testing because if you find a liver met on progression and you don't have testing, you're already setting yourself up for being behind on making that next decision. So the testing, especially for germline, doesn't change. You can get it as early as you want. Somatic, you can get it any time you have tissue. So I think having that, if we do a better job on our testing percentages, then our treatment will rise just because we'll have that data to make the informed decision.

Zachary Klaassen: Yeah. Any shout out for testing is always a good one on this channel. So I think that's a great summary. So, David, thanks so much for joining us on UroToday.

David Morris: Thank you for having me.