The Future of Adjuvant Treatment for RCC: Biomarkers, Trial Data, and Clinical Challenges

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, a panel of experts discussed the latest research, emerging therapies, and best practices for treating renal cell carcinoma (RCC). Moderator Dr. Katy Beckermann of Tennessee Oncology was joined by Drs. David Braun, Matt Campbell, Brad McGregor, and Katie S. Murray in the discussion.

In part two, the panel covers biomarker-driven treatment approaches, ongoing clinical trials, and how emerging data is shaping the future of adjuvant therapy. They also explore strategies for optimizing patient selection to maximize benefits while minimizing unnecessary treatment.

View the next segment on Triplet Therapy in RCC: Insights from ASCO GU 2025.

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Dr. McGregor: I think when we think about any decision we make in the clinic, it is a shared decision-making. And so I think, it is our job as clinicians to educate patients about where we are at right now. And I think we have a drug, with pembrolizumab, that has been shown to certainly reduce risk recurrence, improve overall survival with the caveats of the trial design. I think that is impressive and I think that should be something that we need to inform our patients about. And if they meet the criteria for KEYNOTE 564, it is something to talk to them. And I agree with everything that some patients will hear their risk benefits and you try to give a better sense of their risk using a shared nomogram. “Hey, that does not make sense.” Others will say it does make sense. And I think, as long as you are having that informed discussion with every patient, I think that is what really needs to be done at the end of the day.

And then as you look forward, I think there is a lot of concern about overtreatment. I also want to make sure we do not under treat. So I always get a fresh set of scans. So I am always like, let us make sure their lungs look great, thyroid looks great. If there, actually, are indeterminate findings where I am like, I do not know what that is, I actually just say, “Listen, I am not sure what this is. If this is kidney cancer, I would be under treating you. I would just favor a surveillance approach because I would hate to under treat you for something in this situation” and go from those lines.

Dr. Campbell: I think that that is right on. And the challenge is, I think, the timing too, of when do you get the scans? And so there are so many patients that have four millimeter, six millimeter pulmonary nodules. And I saw a guy in the last few months who, 56, ECOG zero, a high-power job and he has all the risk factors possible, 10 centimeter tumor, a lot of sarcomatoid, rhabdoid, the whole nine yards with three millimeter lung nodules. And when we get the scans, they are now six millimeters. And this is a guy that I feel very strongly is going to likely relapse and I would feel I am undertreating with a single agent. So those, they are tricky. And so I love the detailed discussion.

Dr. McGregor: And I think, ultimately, though we do need to do better. So as much as those patients who may not relapse with anything, there are patients who get adjuvant therapy and they still relapse. And so how can we improve upon that? So I think, there are biomarkers that say who is the best patient, but you do not just need to know who is at risk for relapse, but is that patient with risk relapse, can we make a difference with a given therapy? And so as we think about that, I think there are different approaches. And so there are certainly approaches that have already completed accrual, looking at pembrolizumab with or without the HIF-2 inhibitor, belzutifan.

I am very honored to be able to lead the Alliance Strike trial, which is looking at a year pembrolizumab with or without six months of tivozanib, which just opened in the past couple of weeks and documents are able for download. But then I think, there are even more different ideas. I had a pleasure to work with David on the NeoVax trial, this idea of neoantigen therapy and trying to, as David says, get the steering wheel there. I know David wants to talk a little bit further about that.

Dr. Braun: And I think, pembro clearly sets a foundation for adjuvant therapy. And I think all the things you said, I agree largely with. I will say, I am probably a little bit stronger on the overall survival. I think there are open questions there, obviously, in terms of subsequent therapies, but we also sort of live in a world of imperfect data and with the data that we have, there is an overall survival benefit and that is a really powerful thing. And so I sort of think of that as the backbone and then how can we build on that? And I have used this silly analogy many times, but this idea, again, if immune checkpoint inhibitors are lifting the brakes, that maybe we can add a steering wheel and really direct the immune system where to go.

And I think when we did that in a phase one setting, it was certainly really promising. We can really get on target immune activity. We did not see, actually, any recurrences though very, very small numbers, but I think this is where the phase two will come in and be really helpful to that V940004 study, to really see their clinical efficacy with this approach.

Dr. Campbell: I just have to say that was a beautiful manuscript and study, so congratulations to your team for being able to do that.

Dr. Braun: No, it was a huge team effort.

Dr. Campbell: Yeah, personalized cancer vaccine, I mean, it is good stuff. So congratulations.

Dr. Beckermann: Yeah.

Dr. Braun: Thank you.

Dr. Campbell: Looking forward to seeing that in larger studies.

Dr. Braun: Absolutely.

Dr. Beckermann: I think that this is, really, what we all think about and deal with when we are seeing a patient and talking to them about adjuvant treatment. It is all these points that everyone has brought up and I think it is not perfect. It is a challenge.