Zachary Klaassen: Hi. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are at AUA 2025 in Las Vegas on UroToday. Delighted to be joined by Dr. John Sfakianos, who is a urologic oncologist at the Icahn School of Medicine at Mount Sinai. John, thanks so much for joining us on UroToday.

John Sfakianos: Oh, my pleasure. Thank you for having me.

Zachary Klaassen: So we're going to talk about, really, risk stratification for microhematuria and how we can make it better, and really, your experience with some of the new biomarkers such as the Cxbladder platform. But before we get into that, maybe just highlight this unmet need for microhematuria for high-quality biomarkers.

John Sfakianos: Thanks. Thanks for doing this.

Zachary Klaassen: Sure.

John Sfakianos: And thanks for having me, of course. And I think we've been looking and looking for really good, high-quality biomarkers in this space for a long time, especially because we were just over-diagnosing or overdoing our diagnostic tests for our patients who were coming in with microscopic hematuria.

Zachary Klaassen: Right.

John Sfakianos: We know the majority of the patients are not going to have anything substantial. We're not going to necessarily find a diagnosis on everybody. And it's a small percentage of patients that are going to have the, quote unquote, "lethal" disease, which is a bad cancer of some sort.

Zachary Klaassen: Yeah.

John Sfakianos: So we used to do cystoscopies on every patient no matter what, and so forth and so on. So I think now risk stratifying our patients is key because we're going to be able to put our patients into these categories and minimize or deescalate what we're going to use or what diagnostic tests we're going to use.

Zachary Klaassen: Sure.

John Sfakianos: So it's been a huge unmet need for many, many years. I think the risk stratification was important. But now I think the next step is really bringing in high-quality markers that have a really good negative predictive value to allow us to say, OK, we did everything. You're fine. Go ahead on your merry way.

Zachary Klaassen: Yeah, absolutely. That's well said. So getting into your practice, what's your experience been with the Cxbladder platform?

John Sfakianos: It's been great. For me, as a bladder cancer focus in my practice, I see a lot of patients, both for hematuria but also for bladder cancer, who have a diagnosis. So there's an unmet need there. You have your patient that's 10 years ago had bladder cancer who's been coming to you for cystoscopy every year. It's negative every year.

Zachary Klaassen: Begrudgingly comes.

John Sfakianos: Yeah, exactly. Like, do I have to come in for this cysto? You know how much I hate this cysto.

Zachary Klaassen: Yeah.

John Sfakianos: And so, really, to try to find a good marker in that space as well has been key.

Zachary Klaassen: Sure.

John Sfakianos: So I think Cxbladder is really-- just has the whole armamentarium. They're going through the gauntlet of the different diagnoses and finding high-quality markers that are going to allow us to deescalate what we're doing for our patients. So you have Triage for the hematuria. You have Monitor for the patients who have bladder cancer. I use both of those in my practice almost routinely with all my patients.

Zachary Klaassen: Yeah.

John Sfakianos: And we've looked at our data. We've had some AUA posters. And we're putting more data together that the negative predictive value is high, right? So if somebody comes in and we do these tests, we can maybe avoid doing a cysto for our patients.

Zachary Klaassen: Yeah, absolutely. We're going to get into Triage with regard to the new update to the guideline, but maybe just talk a little bit more about Monitor, how you use that in your bladder cancer patients.

John Sfakianos: Yeah. So like I started to bring up a little bit ago, for those long-term patients, those patients that have been a couple of years disease-free coming in for cystos, I use Monitor routinely now. I'll have a patient come in-- or the beauty is we can do home tests, which is huge.

Zachary Klaassen: Sure, yep.

John Sfakianos: So we will have these patients do either a home test or come in and give us urine. If it's negative, I will skip a cysto. I will alternate and maybe tailor my cysto surveillance program for my patients based on, obviously, patient comfort, you know--

Zachary Klaassen: Sure. Decision-making with them.

John Sfakianos: --decision-making with them, and so forth and so on. And instead of doing one every six months, we'll go every year. Maybe we don't take it completely away, but we can personalize it a little bit more and have-- and that's because we have a test that I feel comfortable is really a phenomenal negative predictive value. And that allows me the comfort level and the decision-making with the patients.

Zachary Klaassen: Yeah. Great. Great said. I think, when we look at the guidelines, the AUA update for microhematuria presented at-- published recently, but really presented at AUA-- just focus on some of the highlights, but specific to where biomarkers are now really coming into the guidelines.

John Sfakianos: Yeah, it's been many years in the making and a lot of debates.

Zachary Klaassen: Yeah.

John Sfakianos: I do think that we've gone through many different biomarkers. I think personally, what always is the case-- and we see this, for whatever reason, a lot in the bladder cancer space, the data is-- or let's say the tests are performed with as little data as we can possibly get.

Zachary Klaassen: Yeah.

John Sfakianos: And then they just get pushed and accepted into clinic and pushed and pushed and pushed.

Zachary Klaassen: That's right.

John Sfakianos: And as you use these, you realize, well, it's not as good as what we thought it was because the right data collection, the right trials weren't performed. And so for many years, this has been a little bit of a yin and yang type of--

Zachary Klaassen: Especially for guidelines, I want high-quality data, right?

John Sfakianos: Exactly.

Zachary Klaassen: Yeah.

John Sfakianos: But it's also within the community. These have been discussions within the community for a long period of time. And not that we've had too many-- I don't want to use, conflicts, or, you know?

Zachary Klaassen: Yeah, sure.

John Sfakianos: But it was always, in my opinion, the lack of data.

Zachary Klaassen: Yeah.

John Sfakianos: And I think now we're actually seeing that we are getting high-quality data. We're doing properly performed trials with these tests. And that's giving more confidence to the guideline panel members to allow incorporation into the guidelines. So I think this is key. The wording is still pretty loose, which is still important as well. But they're actually at least recognizing high-quality biomarkers.

Zachary Klaassen: Yeah. And this goes back to the STRATA trial that was published. And this is the first level 1 biomarker-driven trial that has made its way into the guidelines as well.

John Sfakianos: Right. I mean, then when you do that kind of study, you have no choice but to accept what the data is, which is great.

Zachary Klaassen: It's what we need.

John Sfakianos: It's great for the field.

Zachary Klaassen: Yeah.

John Sfakianos: And hopefully, that sets a precedence for any other markers and any other tests and other therapies that we want to bring in.

Zachary Klaassen: Yeah. Last question, just kind of taking the guidelines and at a broader application across the country, let's say, what is the impact of a guideline update that now has evidence-- level 1 evidence-- for biomarkers and really appropriately triaging patients, hopefully to lower risk, but if they're higher risk, also knowing that we have the confidence to say, we need to do a full workup? What's the big implication that this could have on the community?

John Sfakianos: Yeah. I think this allows us, now, like I said a little bit before. I mean, within the guidelines, the biomarkers are really focused around the intermediate risks because the low risks-- I mean, I would probably use it for both cases to try to help tailor and share decision-making with my patients if we're going to do a cysto or not.

Zachary Klaassen: Mm-hmm.

John Sfakianos: In my practice, the way these things have changed is traditionally, I would see a patient and say, OK, we're going to set you up for these tests and a cystoscopy. And now it's, we're going to set you up for these tests. And if they're all negative, we'll just set up a follow-up appointment for you, rather than everybody just going straight to cysto.

Zachary Klaassen: Right.

John Sfakianos: I mean, I think for the high-risk patients, we still have to bring in the cystoscopy. But now this allows us a little bit more leniency in how and who we do cystoscopies on, which I think is really important.

Zachary Klaassen: For sure. Great discussion, John. I think I've really enjoyed it. And I know our listeners will, as well. Maybe just a couple take home messages before we wrap up.

John Sfakianos: Yeah. Thank you very much, again.

Zachary Klaassen: Of course.

John Sfakianos: And for me, I think it's, guidelines are important. They're not necessarily rules, but they're important to incorporate into our practices. And I think guidelines just allow us that ability to move forward and change and shift without being overly concerned that we're jeopardizing our patient care.

Zachary Klaassen: Right.

John Sfakianos: And when you have biomarkers like Triage, which has a negative predictive value of 99% or 100%, which is really phenomenal, it really should be a part of the tool kit that you have in helping diagnose your patients with microscopic hematuria.

Zachary Klaassen: Excellent. John, thanks so much for your time on UroToday.

John Sfakianos: My pleasure. Thank you very much.