PEACE-3 and the Role of Radium-223: Rethinking Combination Strategies in mCRPC

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, an expert panel convened to discuss the latest research and clinical advancements in prostate cancer diagnosis and treatment. Moderated by Dr. Alan Bryce, City of Hope, Arizona, the roundtable consisted of Dr. Alan Tan, Vanderbilt; Dr. Evan Yu, Fred Hutch/University of Washington; Dr. Priyanka Chablani, UPMC; Dr. Jack Andrews, Mayo Clinic Arizona; and Dr. Chad Tang, MD Anderson Cancer Center.

The panel examines the PEACE-3 trial and its implications for radium-223 in combination with enzalutamide for mCRPC in the fifth segment of their conversation. The panelists discuss whether this overall survival benefit could bring radium back into routine practice, particularly for older patients or those ineligible for chemotherapy. The conversation also explores the broader question of maintaining ARSI therapy when adding new agents like radium, pluvicto, or PARP inhibitors.

View the next segment on Key Takeaways From ASCO GU 2025: TALAPRO-2, PSMA PET, and Emerging Treatments.

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Dr. Bryce: Now, I’ll shift course here. What about PEACE-3? This shifts, this is an interesting data set, enza-radium combination. Where does that fit in? Because radium has kind of faded from the scene a little bit. Does this bring it back in? I mean, Alan, maybe I’ll have you speak to the audience here.

Dr. Tan: Yeah. This was presented at ESMO. And so, this is in a little bit of a different population than a contemporary population, because these patients did not have ADT and ARSI up front like we do currently in the United States. So, it’s really a very compelling study. I mean, it’s prime at any point. But I think a lot of us are confused of how to use this in a real world, similar to how we do PARP inhibitors, because we’re not using ADT alone in the frontline setting.

Dr. Bryce: What do you think?

Dr. Chablani: I mean, it hit OS, so that’s amazing. I do think it brings radium back from behind the curtains into the forefront. I do think it also becomes a good option for patients who’ve progressed on like ADT plus ARSI, and then they’re in their 80s, they have comorbidities, they can’t get docetaxel, they don’t want docetaxel, they have fears of chemo. So they’re not going to be able to get pluvicto. And we don’t have an approval for pluvicto prior to docetaxel. So, what do I do next? So for those patients that I’m seeing in clinic, I’m referring them to nuc-med for radium-223. And I’m telling them to keep their enzalutamide on, because of that synergy that we saw in that study. And I think we saw some other studies today, the ENZA-p study that’s also demonstrating a synergy between enzalutamide and pluvicto.

So I think some of these questions that are… We’re seeing these combinations have synergies in the metastatic castrate-resistant setting, but they’re in a vanishing population. It’s all in people that were on ADT alone, and they developed castrate-resistance. And now we’re using these combinations. But my question is, if we’re moving ARSI up front, and now everyone’s getting ADT plus ARSI and then they’re progressing, can we use the synergy that we’re seeing from these combinations and the safety to say, “Okay, well, let’s keep the ARSI on and add radium. Let’s keep the ARSI on and add enzalutamide, or olaparib, abupred, or pluvicto. Pluvicto again, is not approved yet, but maybe it will be in the future.

And then do we just keep that ARSI on, and add the pluvicto and embrace that synergy? I think these are questions that we need to be thinking about in our clinics, because we’re not going to have readouts from these randomized trials for years. So it becomes very relevant.

Dr. Bryce: I think you hit on the most important point for PEACE-3, is there is an overall survival advantage. It’s a strong signal. It’s a very impressive signal. So I think it absolutely puts radium enza combination in play, something we ought to be thinking about. But the other key message in the public service announcement we have to put out is the importance of the bone strengthening agents, right?

Dr. Chablani: Yeah, absolutely, 100%.

Dr. Bryce: We see this in the real-world data. Only half of patients at best are getting Zometa or denosumab as they should. Men with castration-resistant metastatic prostate cancer and bone mets should absolutely be on bone strengthening agent. And in PEACE-3, there was a dramatic difference in the skeletal related events before and after the mandated use of the bone strengthening agents. So kind of key takeaway points from this session for people is, please don’t forget your bone strengthening agent. Please don’t forget your germline testing. Please don’t forget your NGS.

These are things that are clearly lacking in practice in the United States right now. We really need to expand this. But I think the good news with PEACE-3, with all of our hormone sensitive studies with ARANOTE, other studies is, we have an ever expanding list of options. I think we certainly appreciate that the decision-making gets more difficult, but this is a wonderful problem to have, right? This is where we want to be. We want to have lots of options for our patients, and to be able to apply good clinical judgment.