Biomarkers, Testing Gaps, and Emerging Strategies in Prostate Cancer Care

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.

In the first part of their conversation, the panelists discuss advances in biomarker testing, treatment intensification, and best practices for integrating next-generation sequencing into clinical prostate cancer care. They also review the clinical impact of TALAPRO-2, gaps in biomarker adoption, the role of germline testing, and challenges in circulating tumor DNA interpretation.

View the next segment on Expert Insights on the Benefits and Limitations of PSMA PET Imaging for Prostate Cancer.

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Dr. Bryce: Hello, everyone. Thank you for joining us on this GU Oncology Now Prostate Cancer Roundtable. We’re here today at GU ASCO 2025 to talk about the latest advances, techniques, and approaches in advanced prostate cancer. I’m your moderator, Alan Bryce, a medical oncologist at the City of Hope Cancer Center in Arizona. I’ll have the panel introduce themselves.

Dr. Tan: I’m Alan Tan. I’m a GU medical oncologist and associate professor at the Vanderbilt University Cancer Center in Nashville, Tennessee.

Dr. Yu: Good evening, everyone. I’m Evan Yu. I am at the Fred Hutch Cancer Center and University of Washington in Seattle. I’m a GU Medical Oncologist.

Dr. Chablani: Hi everyone. Thrilled to be here. My name is Priyanka Chablani, and I’m a GU Medical Oncologist and assistant professor at UPMC in Pittsburgh.

Dr. Andrews: Good evening. I apologize, I’m losing my voice. My name is Jack Andrews. I’m a urologic oncologist at Mayo Clinic Arizona.

Dr. Tang: Hello. My name is Chad Tang, I’m a radiation oncologist and associate professor at MD Anderson Cancer Center in Houston.

Dr. Bryce: All right, very good. Well, thanks for being here, everybody. What we want to provide tonight is a discussion around what we think are some of the burning questions in prostate cancer management today. Dr. Chablani, let’s go ahead and start with you. We’ve heard a lot at GU ASCO today about biomarkers and the approach to testing in patients, also about the deficits, and what is the gap between guidelines and practice in the United States? I guess, where would you start in terms of speaking to the audience? What should we be doing in biomarker testing in prostate cancer today?

Dr. Chablani: So yeah, so relevant, especially with the TALAPRO-2 data today that was shown. But I do think we need to be doing NGS on every single patient that comes in with metastatic prostate cancer. So I usually do that on the prostate biopsy, or metastatic site biopsy. And then I also do germline testing for everyone that I can. I usually start with the NGS, at least get that going. And then later on speak to patients about germline testing.

The first visit is a lot for patients, with talking about ADT plus ARSI, maybe adding a triplet, reviewing PSMA PET scan results. Or if they don’t have complete imaging, ordering additional imaging. So, we definitely have a lot of data now. So we have a lot of data points that we can follow, which is great. But we absolutely have to be ordering NGS and germline. And then obviously, there’s a role for ctDNA, as well, as was discussed today, particularly in patients who we don’t have NGS or good prostate biopsy, metastatic site biopsies. I am sending the ctDNA testing to try to assess for high-risk aggressive mutations.

Dr. Bryce: Yeah, fair enough. I mean, Dr. Yu, obviously, University of Washington has done a tremendous amount of work really defining this field for all of us. But where is the gap in testing? How come we’re not seeing uptake? And what is it that the busy clinician needs to do to incorporate this into their practice?

Dr. Yu: Yeah, I mean, I think the real reason why there hasn’t been this huge uptake in prostate cancer is that, unlike some other diseases where in the first line you’re a fellow or student, you present a patient. It’s like if it’s a breast cancer patient, it’s ER/PR/HER2. If you’re lung cancer, EGFR, ALK, ROS1. We don’t have that yet in prostate cancer, and maybe we should be moving in that direction where it just puts it right on the forefront of everyone’s brain.

But I agree completely with Dr. Chablani. Everybody with metastatic prostate cancer absolutely needs to get somatic testing, next-generation sequencing, and absolutely needs to get germline testing, because it has really broad implications beyond just that individual patient you’re looking at.

I mean, of course for that patient, you want to be able to help that patient and fine tailor treatment that’s precision medicine-focused if you can. But beyond that individual, they may have inheritable mutations that their loved ones or siblings, their offspring may have inherited. And it could have implications for many cancers beyond prostate cancer—pancreatic cancer, ovarian cancer, endometrial cancer, breast cancer, you name it.

And our goal is for those individuals to eventually, hopefully be identified. Early screening programs identify that when the cancer is very early, and cure those patients, and save a lot of lives down the road. So that’s the goal here, and that’s why this is all incredibly important to do all this testing.

Dr. Bryce: Yeah, yeah. And let me give you a follow-up here. Because again, the University of Washington group has really done some important work about clonal hematopoiesis, and the confusion we get from the ctDNA results. So what message would you try to impart to the audience about that in prostate cancer?

Dr. Yu: Right, great issue to bring up is CHIP as we call it. That’s when you’re doing circulating tumor DNA, or looking for exactly that—tumor DNA in the blood. But there can be age-related clones, old white blood cells, and you can find alterations oftentimes in big genes like ATM.

These are just kind of old clones that are hanging out. And the reason it’s called indeterminate potential is, we don’t know what it means. We don’t know what it means. But what can happen is, sometimes you can get alterations in these big genes that you can mistakenly think might be related to your prostate cancer.

And what you don’t want to do is have a false positive that leads to you treating a patient with something like a PARP inhibitor, when they really don’t have a homologous recombination deficiency gene alteration. And so, it’s important to look when you’re doing circulating tumor DNA, look at the allele fraction, I always ask for zygosity, is it monoallelic? Is it a biallelic alteration?

There’s a lot of things to look at to avoid false positives, because you can overtreat and it can lead to excess toxicity and not benefit the patient.

Dr. Bryce: Yeah. Absolutely. That’s fantastic. What about Dr. Tang, from the radiation oncology perspective, we have a lot of different guidelines. We’ve got AUA, we’ve got ASCO. But there’s consensus that all high-risk, very high-risk patients should have germline testing. So it’s not just metastatic disease. And yet we know again real data, there’s a gap there. So what about in the radiation oncology world? Is there an educational gap we’re missing? How do you all talk about best practices, and what message should we be conveying to the audience?

Dr. Tang: Yeah. So, it’s all very practice-dependent. Sometimes for high-risk prostate cancers, they’re seeing the med-onc at the same time, and usually sometimes they’re seeing them first. So often they’re approaching the topic about genetic testing, and getting that to guide their therapies.

For us, I agree, we probably don’t do it as much as we should be talking about in the field, but that’s something I think we’re getting more aware of, but we do need to keep it in the forefront.