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Moving Beyond DNA: The Role of Early, Multi-Modal Genomic Testing in Prostate Cancer Management - Colin Pritchard

November 19, 2025

Zachary Klaassen hosts Colin Pritchard to discuss genomic testing advances in prostate cancer. Dr. Pritchard emphasizes the importance of early genomic testing in metastatic and castration-resistant disease, noting that germline variants remain stable throughout life and most targetable somatic mutations are relatively consistent over time. The conversation highlights emerging biomarkers including PTEN, which serves both prognostic and predictive roles for AKT inhibitor response, and circulating tumor DNA for therapeutic monitoring and minimal residual disease detection. Dr. Pritchard envisions a future of multi-modality testing integrating DNA-based genomics, RNA expression patterns, methylation analysis, and broad proteomics, ultimately progressing toward comprehensive whole-genome, transcriptomic, and proteomic approaches. The discussion concludes with Dr. Pritchard encouraging clinicians to establish relationships with molecular pathologists to navigate increasingly complex genomic results and optimize personalized treatment strategies for patients.

Biographies:

Colin C. Pritchard, MD, PhD, Professor and Director, Genetics and Solid Tumors Laboratory, UW Medical Center, Seattle, WA

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA



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ASCO GU 2025: Evaluating Associations Between Genomic Classifier and Digital Pathology–based Multi-Modal AI Biomarkers in Oligometastatic Castration-Sensitive Prostate Cancer

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Read the Full Video Transcript

Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center, and I'm delighted to be joined on UroToday by Dr. Colin Pritchard, who is a pathologist at the University of Washington in Seattle, Washington. Today we'll be talking about genomics in 2025, and yes, it's a broad topic, Colin, but thank you for joining us and breaking down genomics for the next few minutes.

Colin Pritchard: Well, I'm really pleased to be here. Thanks for the invitation.

Zachary Klaassen: Always good to chat with you. But I think when we have these conversations, super important for our listeners to hear over and over again just to who we should be testing, who the oncology team should really be targeting.

Colin Pritchard: Yeah, it's a great question because it's expanding for prostate cancer. Certainly in the metastatic setting and in the castration-resistant setting, there are now cleared guidelines for testing genomics, mostly for PARP inhibitor, but also for immunotherapy. So those are the sort of main two indications. And in the metastatic setting, also germline testing is recommended in guidelines.

Zachary Klaassen: Right.

Colin Pritchard: But increasingly, we're seeing lots of scenarios where we want to know genomics earlier on in the disease process. So that's exciting for me as a molecular pathologist.

Zachary Klaassen: Absolutely. And so you kind of alluded to it a little bit in terms of maybe treatment selection, but why on a high level is it important to test these patients early on? And like you said, high risk, locally advanced, all the way through MCRPC, but why is it important to get that information early?

Colin Pritchard: Well, I mean, if we get the information before we need it, that's ideal, right?

Zachary Klaassen: Yes.

Colin Pritchard: The nice thing about a lot of this genomic information, if we take the germline, the inherited variants, those aren't changing. You were born with those.

Zachary Klaassen: Sure. Yeah.

Colin Pritchard: So that's going to be the same throughout your life. So if something in there is informing your treatment, why not learn it earlier if you can get the testing done and guidelines? But also is true for the somatic or acquired mutations in tumor. A lot of times we'll see our providers will order something for the next line of therapy and they don't even need it for many months or maybe even a year later. The nice thing about the genomics, they do evolve over time as cancer progresses, but most of the genomic findings that we're trying to target in prostate cancer right now in 2025 tend to be relatively stable, which is good news in terms of, so why not try to get it so you have it in the bank? I think that's one of the main reasons.

Zachary Klaassen: That's a great answer. I think we're coming off the heels of ESMO where we saw the importance of PTEN and testing for that. So how have things changed in the last year or so? What's exciting in your mind as how things have sort of evolved and how that's going to be more important for personalization of medicine?

Colin Pritchard: Yeah. I mean, PTEN's a great example. That's something we can do by immunohistochemistry, but it can also be done by genomics or next generation sequencing. It's exciting because that's a new biomarker that looks like it's predictive of AKT inhibitor response, although that data's still emerging, but it looks like that's probably going to be true. But also, I think what's definitely true is that it's a prognostic biomarker. So it's exciting that we are getting indications for genomic testing, whether it be at the protein level by IHC or actually looking for the gene mutations, not only for the purposes of strictly treatment, but also for prognosis and how that helps you manage the patient. So PTEN is a great example of that. That's not really widely in practice yet, but I think we're getting to the point where that's going to be probably recommended pretty soon to be done.

Zachary Klaassen: We've heard a lot about ctDNA over the last little bit too. So what are your thoughts just at a high level on how that correlates with tumor tissue? We've seen it in bladder for sure in the last little bit with IMvigor011. So if we're going to see an uptick of ctDNA, which you probably will, how does that relate to you guys as molecular pathologists?

Colin Pritchard: Yeah. I mean, ctDNA is such an exciting thing. I mean, we can sample the mutations that are shed from the cancer. We can monitor over time. I think there's going to be an increasing role for the molecular pathologist in interpreting ctDNA. It's a tricky thing.

Zachary Klaassen: Sure.

Colin Pritchard: We've heard a lot about minimal residual disease testing, which might be coming on board for prostate cancer too. So that's sort of a new indication for ctDNA. The other sort of indication for ctDNA that's not quite there yet, but there's some emerging data is therapeutic monitoring. So not just looking for the mutation, I'm going to drug this. That's sort of what we have right now. So you have widespread metastatic disease, you're looking for the target, that's the mainstay of ctDNA testing. But these other new indications like therapeutic monitoring, looking for just the level of ctDNA going up and down, or even minimal residual disease, looking for the tiniest little bit that might be there that might even tell you that the cancer's there even before the PSA does. So those are exciting new indications that are coming along and are making the space more complex, but fun for someone like me who does this for a living.

Zachary Klaassen: Absolutely. Absolutely. No, I think too, I mean, to be able to predict recurrence or a poor outcome before PSA or even imaging uptake, I think as we sort of see technologies cross different GU cancers, and I think that's where, from a clinician, that gets exciting because you sort of see some overlap there. I want you to sort of, as your wishlist over the next say, couple years, how would you see the field evolving, not just for diagnosis, but for precision medicine for patients?

Colin Pritchard: Yeah. I think what we're going to be seeing in the next few years is multi-modality testing. So what I mean by that is not just DNA-based mutation testing. I mean, we've talked about PTEN, that's a modality looking at IHC biomarkers combined with DNA-based genomics, but also RNA, right?

Zachary Klaassen: Yeah.

Colin Pritchard: So we're increasingly seeing roles for RNA, for expression patterns, for example, looking for emergence of neuroendocrine disease, but also other RNA based biomarkers. And then fast-forward a little bit forward from that, methylation or epigenetic based biomarkers, which we've learned a lot about at this meeting and are coming along. And then ultimately broad-based proteomics beyond just looking at one protein by IHC. So in the next couple years, I think we're going to see things like IHC plus DNA NGS plus some RNA. Fast-forward five, six years, we'll probably see more of that methylation. Fast-forward another five years, probably things like proteomics. And I really view the end game in this space as whole genome sequencing at the DNA level, whole transcriptomic, all the RNA, and probably whole proteomic and epigenomic. I mean, all the -omics is where we're going eventually, and it's going to get really complicated, and we have to establish clinical utility for all these to be clear. Just because we can do these things doesn't mean we should. But as we establish clinical utility for all these modalities, I think we're going to be adding them on and having these multimodal approaches to testing.

Zachary Klaassen: Super exciting. Always good chatting with you about genomics. Any last minute thoughts for listeners, any take home messages, anything we haven't hit on?

Colin Pritchard: I think this is great. Just my plea to the clinicians out there, make a relationship with your molecular pathologist if you have one.

Zachary Klaassen: I love it.

Colin Pritchard: If you don't have one and you're using your reference labs, make a relationship with someone who's an equivalent in your reference lab so you have someone to talk to about these complex results.

Zachary Klaassen: Great take home message. Colin, thanks as always for joining us.

Colin Pritchard: All right. It was a pleasure to be here. Thank you so much.

Zachary Klaassen: Awesome.