Molecular Biomarkers and Risk Stratification in High-Risk Non-Muscle Invasive Bladder Cancer

For the final part of their roundtable conversation, Roger Li, MD, Vitaly Margulis, MD, Kyle Rose, MD, and Paul Crispen, MD, share their insights on risk assessment, the impact of molecular biomarkers, and customized treatment strategies for high-risk non-muscle-invasive bladder cancer. This discussion sheds light on the hurdles of aligning clinical trials with real-world practice, explores the promise of precision-targeted therapies, and examines the evolving landscape of personalized medicine in NMIBC management.

Watch this series from the beginning: Navigating the BCG Shortage: Gem/Doce and Clinical Trials for NMIBC

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Dr. Rose:
I have a question for the group if that’s okay. I’ve noticed in clinical trials, they’re very much guided by the risk category. In your practice, are you using NCCN guidelines or are you using IBCG? How are you stratifying these patients?

Dr. Margulis:
I can tell you, in my practice it’s high risk, and then there’s everything else. Really, right? Because that’s mainly what you’re going to make your decisions based on. So this intermediate risk category, it’s a little bit murky. It’s kind of a rare patient group, and it’s not as clinically important to me. So for me, again, I just go, “Is this high-risk or not?”

Dr. Li:
And you go by the grade for determining whether they’re high risk?

Dr. Margulis:
Correct.

Dr. Crispen:
I use the AUA guidelines for those or whatever the clinical trial that we have available is going to allow to get them into that study. But I think as long as you’re being thoughtful about it and not giving BCG too early, though… I think we’ve talked about this, how we’ll have patients come in, I’m sure you see it all the time, unfortunately, where you have patients come into your practice that maybe shouldn’t have received BCG but have received it, it kind of creates that problem.

Dr. Rose:
Sorry. That’s where I was going with the question is that we have low grade patients who fit into intermediate risk that are getting BCG, and now they’re not eligible for some sort of trial that we have to offer. So the risk stratification and AUA versus IVCG, I found some cross-contamination there.

Dr. Margulis:
Yeah, I think you’re getting into the clinical trial design issues and your clinical practice and clinical judgment. Those don’t always exactly overlap.

Dr. Li:
True.

Dr. Crispen:
Since we’ve got Roger here, as the moderator, it’s a great discussion, but we’ve got the pioneer in kind of the molecular biomarker space and predictors of response. And for you, what do you think is going to be that next step of maybe… Are we going to be able to select which therapy is going to be the right choice for a patient in the future? And how are you doing that?

Dr. Li:
Yeah, no, that’s a great question, and I think a very important question, because eventually, the way that I look at this, so BCG unresponsive, the definition is already selecting out these patients that are not going to be responding to BCG. So we’re actually using this definition as a biomarker for putting patients on alternative therapies. The question truly becomes like, are we going to be able to do this in the frontline setting? And so, I think certainly looking at the tissue, looking at things like circulating tumor DNA, those are going to be the answer. But how are we going to be able to approach it and tailor it to different therapies and the mechanism of action of the different therapeutic agents?

I think we’ve been at this with BCG, as you pointed out, for decades. We still don’t quite have it yet. Same thing with chemotherapy. But hopefully with the molecular biomarkers we’ll be able to see some patterns that maybe the human eye can’t even see. And we can depend on the artificial intelligence and others to show us the way.

Dr. Margulis:
There’s some good work in the muscle-invasive line of cancer. They have these immune-responsive profiles, they have the chemotherapy-responsive profiles. So there’s some data. I don’t think we’re really utilizing it in this space yet. So there’s ways to do this thoughtfully. I think with erdafitinib for example, I’m very excited that we have now a targeted treatment. So I think if I have a target, that would be my frontline treatment, right? If that’s available in front line, I would go after the molecular target. So having products that specifically are targeted, I think it’s a huge step forward.

Dr. Li:
For sure.

Dr. Margulis:
And finally, I’m hoping we’ll have something intravesical-targeted soon.

Dr. Li:
So this wraps up our session. I think we’ve had a really wonderful discussion about all facets of taking care of patients with non-muscle-invasive bladder cancer, high-risk non-muscle invasive bladder cancer. We very much look forward to the upcoming years where a lot of these data are going to emerge. Thank you very much.