Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We are at AUA 2025, in Las Vegas. I'm joined on UroToday by Dr. Ron Loo and Dr. Chris Filson, both urologists at Kaiser Permanente in Southern California. Gentlemen, thanks so much for joining us on UroToday.

Christopher Paul Filson: Glad to be here.

Ronald K. Loo: Thank you.

Zachary Klaassen: So you guys have a huge system. We're just talking offline of how big Kaiser is. And today we're going to talk about Cxbladder triage and how this has been implemented into the microhematuria workup. So maybe, Ron, I'll just ask you, what's the unmet need for not just biomarkers but high-quality urinary biomarkers in this space?

Ronald K. Loo: Well, there's an immediate need that we have. It was manifest even more so with COVID coming.

Zachary Klaassen: Sure.

Ronald K. Loo: In our particular system, we get approximately 20,000 referrals a year for our hunter doctors to manage. And as urologists, we all know that the yield from these workups is exceedingly low.

Zachary Klaassen: Yeah.

Ronald K. Loo: And microscopic hematuria we know is actually not a reliable indicator. And as the years have gone by, the AUA has evolved their guidelines to become more risk-stratified.

Zachary Klaassen: Right.

Ronald K. Loo: For us, having to manage all of the workups, which mainly involves cystoscopy and imaging for these patients, becomes very onerous. We actually couldn't get patients in for almost six months during the peak of COVID. So we were looking for a way to be able to further risk-stratify these patients and see who could safely avoid having to have cystoscopy done.

Zachary Klaassen: Right.

Ronald K. Loo: Fortunately, we've been looking at this particular biomarker called Cxbladder triage for about three or four years before COVID hit. We did some validation studies to prove it did what it did-- has a very high negative predictive value, which was actually better in our testing.

And so we started using it a little before COVID. When COVID hit, we started using it more in earnest. And from a workforce standpoint, from a patient safety standpoint, from being able to get them in, get them worked up properly, from being able to triage the patients properly, to see who needed to get in, who could safely avoid treatment, it was huge for us.

Zachary Klaassen: That's awesome. That's a great background. Chris, I'll spin it to you to talk about just the study design for this current study presented at AUA.

Christopher Paul Filson: Yeah. So there are numerous existing publications supporting the basic utility of this urine-based biomarker that were done prospectively in limited fashion. And to Dr. Loo's point, we wanted to examine what's going on in the real world within the Kaiser Permanente Southern California system with this test, in terms of the impact it may have on the use of cystoscopy, CT urograms, as well as the cancer detection that was seen among tested patients.

So to do so, we essentially identified just over 3,300 patients that had undergone this testing following September 2021 over the course of three years, and then matched those tested patients with a similar cohort based off the date of their encounter, as well as their risk of cancer based out of a previously established hematuria risk index that we had utilized within Kaiser.

Zachary Klaassen: Awesome.

Christopher Paul Filson: And basically, those two groups of patients were compared and stratified based off of the result of the Cxbladder test that was done among the tested patients.

Zachary Klaassen: Awesome. And maybe just highlight the key results for our listeners that you guys presented.

Christopher Paul Filson: Yeah. So what we found was essentially, among the tested patients that were deemed to have a low probability of underlying urothelial cancer, the utilization of cystoscopy was negligible. Basically, if you looked at the matched patients that had similar risk profile, there's about a 45% rate of cystoscopy among those patients. But the tested patients that were similar to that group that had a low probability, less than 5% of that group underwent cystoscopy. So it definitely dropped the number of cystoscopies that were being performed, in terms of hundreds of patients.

Zachary Klaassen: Yeah.

Christopher Paul Filson: So it was clearly a marked drop-off for patients that potentially would not benefit from that invasive procedure. On the flip side, the patients who were tested that had a higher probability or perceived risk of underlying urothelial cancer actually had a greater proportion of cases that underwent cystoscopy compared to the matched cohort. It was about 75% to 45%. So you, on the flip side, see that the patients who needed it most got that test, which was important.

So similar patterns were seen with CT urogram. And I think the biggest thing to show with this is that overall fewer tests were done, for the whole group, but the cancer detection was unchanged overall. And in particular, the patients that were deemed high-risk, there was a greater yield of cancer cases that were detected. So it was really a win-win--

Zachary Klaassen: Yeah.

Christopher Paul Filson: --examining the outcomes related to the real-world use of this useful and significantly impactful urine-based biomarker.

Zachary Klaassen: It's great results. I'm going to break the next question into two parts. I'll ask you, Ron, just from the patient standpoint, when you have this test, how does this shared decision-making work, both for a negative test and for a positive test?

Ronald K. Loo: Yeah. When we were looking at ways that we could risk-stratify the patients, we first wanted an ultra-safe test that had a very high negative predictive value where we could recommend to our patients, you have blood in your urine. You've been sent to see us. We need to figure out and make sure you don't have bladder cancer. That's the primary goal.

We could bring you in, and we could do the traditional workup, which is cystoscopy and some imaging. Or we could test you with this urine test. And while it won't tell us definitively if you do have cancer, it will almost definitively tell us whether we don't need to worry about you, and you can avoid having additional workup.

Zachary Klaassen: Right.

Ronald K. Loo: But if the test happens to be positive, it doesn't mean you have cancer. But we want you to agree that you're going to come in and see us so we can get the workup completed. And the patients really bought in. And if you think about it, for all the patients that we see, you offer them a urine test. And 3/4 of them never need to have a cystoscopy done or be exposed to radiation or imaging. But if it is positive, it doesn't mean you have cancer. But it's at least reassuring that we're doing a little extra testing.

Zachary Klaassen: Yeah.

Ronald K. Loo: And sure enough, twice as many patients actually opted to come in and see us. And so it's been a win-win as Dr. Filson mentioned.

Zachary Klaassen: Awesome. Chris, from your HSR background, same sort of question, but from an economic and utility standpoint, how do you think, from a really broad spectrum, this could change economically and just the health system in general?

Christopher Paul Filson: I think there's no question that there's resource limitations in any practice setting that there is-- be it regionally, across Southern California for Kaiser Permanente, or even within a single large urology group practice. You only have so many appointment slots. You only have so much you can do. And so it's important to allocate those resources to the patients that would benefit most from cystoscopy, et cetera.

Zachary Klaassen: Sure.

Christopher Paul Filson: So I think, at a system level, utilization of this test could more appropriately allocate these tests that can be expensive too and costly depending on the circumstance. So in terms of the dollars and cents, I think that's one thing to think about. And then from the radiation perspective from CT scans, et cetera, as well as the resource allocation, minimizing those types of exposures to patients, I think, would be important at a population level as well, which could be ultimately beneficial for these patients. So I think there's a lot of upside from this test.

Zachary Klaassen: For sure. Great discussion, guys. I think really highlighting some great data presented at AUA and some of the impact of it. Maybe just the take-home message from each of you on this disease space in general and your data. Chris, I'll start with you.

Christopher Paul Filson: Yeah. So I mean, super exciting.

Zachary Klaassen: Yeah.

Christopher Paul Filson: I've got some experience in the prostate cancer space with the role of MRI, guiding biopsy decision-making and other invasive tests that have some burden with it, and to know that we're moving towards, as the guidelines that were discussed at the AUA this year highlight, a way to more properly risk‑align these invasive tests to the patients that need them.

Zachary Klaassen: Yeah.

Christopher Paul Filson: The Cxbladder based on this real-world analysis does have utility, is effective, can appropriately align care to the patients that need it most. And it's important and great to see.

Zachary Klaassen: That's great. Ron.

Ronald K. Loo: Yeah, I think our whole goal as urologists in this space is we're trying to reduce the morbidity and mortality from bladder cancer.

Zachary Klaassen: Yes.

Ronald K. Loo: And I think creating effective strategies moving forward to early identify patients with bladder cancer is going to take a multimodal approach. And as we start transitioning away from hematuria as a sole marker and start risk‑stratifying the population, figuring out who's at risk, we don't have the resources anywhere to be able to cystoscope the mass population.

Zachary Klaassen: There's not enough of us.

Ronald K. Loo: That's right.

Zachary Klaassen: Yeah.

Ronald K. Loo: But if you can identify patients at risk and then further risk‑stratify them with a urine test and be able to safely avoid having to worry about those patients, then we may have a chance of being able to bring in the patients truly at risk-- get them in, get them worked up, get bladder cancer diagnosed earlier, and finally, reduce mortality from this terrible disease once and for all.

Zachary Klaassen: Yeah. Great way to summarize it. Thank you both for joining us on UroToday.

Ronald K. Loo: Thanks so much.

Christopher Paul Filson: Thanks.