Oligometastatic Prostate Cancer: Treatment Strategies and the Role of Local Therapy

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.

Part three of this roundtable discussion explores the evolving role of metastasis-directed therapy (MDT) and local treatment strategies in prostate cancer, particularly in oligometastatic disease and low-volume metastatic hormone-sensitive cases. Topics covered include the potential to delay systemic therapy with MDT, patient selection criteria for PSMA PET-guided radiation, and ongoing trials like SWOG 1802 evaluating surgery and radiation in metastatic disease.

View the next segment on Treatment Selection in mHSPC: ARANOTE, STOPCAP, and the Future of Precision Therapy.

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Dr. Bryce: Following up on the point a little more, let me ask you, Dr. Tan, what about oligometastatic disease? A hot space, especially with PSMA PET, what do we do there?

Dr. Tan: Right. I think metastasis-directed therapy, and Chad can confirm, is really a hot topic across all GU tumor types, and probably across all solid tumors. When we commit a patient to systemic therapy, that’s an indefinite thing a lot of times too. So, if a patient has oligometastatic disease, for example, maybe a few sites of disease, a rib met, a lymph node, et cetera, I think this is an area we need to explore, sparing these patients systemic therapy. ADT, we may prescribe it like it’s candy, but in reality, ADT is pretty brutal for a man. You’re taking away their sexual function, they’re getting hot flashes, you’re getting gynecomastia.

Patients with metastatic prostate cancer, they’re generally elderly. And so, these patients probably have pre-existing coronary artery disease as well. So you’re actually subjecting these patients for a risk of a major adverse cardiovascular event as well. So I think for a patient that has oligometastatic disease, I think PSMA imaging or molecular imaging is the key here. That we can actually pick up oligometastatic disease much better these days, and perhaps target that. But I think Chad might have some opinions too.

Dr. Tang: Okay. So for oligometastatic disease, yes. I think the better the imaging, the better your guidance is for our X-ray beams, the better that we can render the patient to a disease free or disease minimal state. And I think Dr. Tan’s point is well taken. I think that time off systemic therapy or time with U-gonad testosterone is a very patient centric endpoint I think any man with prostate cancer would really much appreciate. So in our practice we like to do intermittent ADT often, and using the PSA center guide that would take off the ADT, usually nine months or two years if it’s intact de novo setting. So, I think a lot of interesting things there.

Dr. Bryce: And what would you consider to be a worthwhile kind of progression free interval. So, a guy comes in three oligomets, you radiate them. Subsequently, he has two more spots. And is there an interval that you would say, “This is too short, this strategy is not going to work,” versus an interval where you’d say, “Hey, let’s just radiate that again”?

Dr. Tang: Yeah. So, one follow up is definitely too short. So if he’s coming back to you in three months in the first follow-up and he has more mets, you’re kind of chasing a losing battle there. But when it’s longer than that, it becomes more of a conversation about the patient like what are their goals? And how have their perceptions of radiation been in their prior rounds? Often they have minimal side effects. So even if the chances are slim, and as long as they’re not re-radiating it, they’re willing to roll the dice at least. So it’s a conversation usually.

Dr. Tan: And to add to that too. A lot of times I feel like the Gleason 7, 3 plus 4s for example, they have more benefit from that than a Gleason 10 that probably will have explosive disease, if you Whac-A-Mole with their disease, right?

Dr. Bryce: Yeah, yep. Fair enough. What about, Evan, when we’re talking about incorporating localized therapy into patients with metastatic disease, the metastatic hormone sensitive patients. Where does that most apply in your practice?

Dr. Yu: Yeah. I mean, I think the most robust data is the STAMPEDE subgroup analysis, I mean, we did initially have the HORRAD trial, which was negative. But that was all kind of very high PSA, very high volume disease patients, and not surprised that radiation of the prostate was negative in that study. We had the STAMPEDE study, where for the overall patient population was negative, but for the low volume disease subset, it was positive for overall survival, and it was a pre-specified analysis. So that certainly makes it a more powerful analysis. What we saw subsequently in the piece one study, was just that we saw a decrease in serious general urinary events, and an improvement in radiographic progression free survival, not in overall survival.

So, it is a situation where overall we have more negative studies than positive studies. But I think it make a lot of sense that the low volume disease subgroup would see benefit. I do think that there are other studies that are still ongoing out there like SWOG 1802, which incorporates not only radiation of the prostate, but surgery to the prostate. And I think it’s reasonable to think about SWOG 1802 for your patients. Because the issue with SWOG 1802 is that it allows either radical prostatectomy, which has not been extensively studied, or with radiation, and actually with more kind of more dealer’s choice, but more people are doing standard full dose radiation, rather than the alternative lower dose radiation that was done in STAMPEDE.

Not saying that you’re necessarily guaranteed better outcomes that way. But I think that for equipoise reasons, the definitive jury is still out. I think it’s something I discuss with my patients that have low volume metastatic disease. But I think because there’s a mix of positive and negative results, I think it’s perfectly fruitful ground to enroll patients in a study like SWOG 1802, and really try to get more definitive data.

Dr. Bryce: Yeah, I mean, Jack, what about 1802, right? How do you talk to patients about this? What should the audience know?

Dr. Andrews: Yeah. So, this is really a conundrum. So, what’s the role of local therapy in low volume metastatic disease? Now I’m going to put a little bit of a target on my head here. Now, I’ll caveat that men with low volume metastatic disease, I send them to radiation. I very rarely operate. If I want to operate, I send them to SWOG 1802. But something that does bother me is that, the limited data that we have that suggests a survival advantage with radiation is done with conventional imaging, particularly bone scan. And there is significant data out there that says bone scan overstages compared to PSMA PET. And so I think the real question is, we need to look at in the PSMA PET era, so when we’re truly detecting metastatic disease in it’s earliest state, is there a role for local therapy at that point? And is it surgery, is it radiation, is it both?

Because I think if we continue to go based on a bone scan, we leave this question up in the air of, was that truly a bone met and they benefited? Or was that a patient who had a false positive and would’ve benefited anyways because they have localized disease? So I think that’s a real conundrum. There’s a little bit of data for… There are definitely stronger data for radiation, there’s a little bit of data for surgery. I think in the meantime, we need to roll on SWOG 1802. But also I think we need to be looking about, how does the role of PSMA PET affect us in this space?

Dr. Tang: So, if I could add to that. So, recently we presented our XMET analysis at ASCO a few hours ago. And there was 500 patients randomized to either radiation or standard of care. And we had a good 100 some patients with choline PET, 100 some with fluciclovine PET, 70 with PSMA PET. And across the subgroups, the benefit of MDT persisted. So although it’s not level one evidence, there is evidence to suggest that even stage better. In fact, PSMA PET was actually the best hazard ratio, and if you look at a point estimate. And the better your imaging is, the better you’re going to be for your MDT. Not that conventional imaging doesn’t have a benefit, but there may be a little bit more noise there.

And also to another point about when we’re doing local therapy for the primary, something that we look for as patients who had prior urinary symptoms from their primary. So I think this is from the PEACE data, if they were having… Sometimes they presented and needed stents in the beginning, or they’re having a lot of LUTS because of the bulky primary, we know that eventually become castrate-resistant, that’s going to be a nidus for progression. Dr. Andrews probably could tell us better than anybody, but those are really intractable problems when you castrate-resistant.

Dr. Yu: Yeah. And it’s a good point. Because a lot of those patients may have very locally expansive disease, and they may not be eligible for SWOG 1802, because you have to be deemed a surgical candidate to be eligible for SWOG 1802. Although what a surgical candidate is, is a little bit subjective. I mean, I would just call Dan Lin and say, do consider radical cystoprostatectomy, and you get the prostate out and the problem’s gone. And then I would-

Dr. Andrews: And it’s surgically resectable after six months of standard systemic therapy. So you can shrink the tumor too and make them resectable.

Dr. Yu: Yeah. I’m only partially kidding.

Dr. Bryce: No. Well so, in a low volume metastatic disease, guidelines now include radiation in a local therapy with radiation. And absolutely SWOG 1802 is going to be important to give us the data for surgery. So it’s a critical data set we have to enroll this study. But the high volume patient, much more controversial. Yeah, we’ve got one data set from PEACE saying, “Look, it decreases obstructive symptoms in the long run.” But it seems to me that what that data set says is, the experienced clinician can apply clinical judgment. I think for the most part, we can look at a high volume patient, we can look at that prostate, we can talk to them about symptoms. And we know who’s likely to get into trouble or not, and talk about either a surgical… Either, let’s do a TURP, or let’s go ahead and send them to radiation. Do we have to radiate everybody to get the PEACE-1 results, or can we just apply clinical judgment? What do you do at MD Anderson?

Dr. Tang: Yeah. So, I think we look at it for a few things. Number one, like I said earlier, if they’re having urinary symptoms initially that resolved transiently, or resolved with ADT, that’s one where we’re worried that it’s anatomically there. Bulky tumors on MRI or on imaging we also worry about. And also small cells or other transformed variants we worry about, when they progress it can be quite explosive. So those are the general features we look for.