Christopher Filson: Well, thank you for that kind introduction, Sam. And I appreciate the opportunity to talk about the work that was done within the Kaiser Southern California system to assess the potential utility of a urine-based biomarker to help guide management of patients who present with microscopic hematuria. As it's relatively well-established, prior guidelines recommended a pretty intense workup for patients who presented with blood in the urine, including invasive cystoscopy and oftentimes upper tract imaging with CT scan and CT urogram.
With the recognition of the potential overuse of radiation associated with imaging studies, as well as the burden of a lot of invasive procedures, there's been a hope that we can find other less invasive ways of working these patients up to really identify those that particularly higher risk of underlying malignancy and sparing the ones who are at lower risk from these invasive tests. And what we wanted to do was utilize a urine-based biomarker called Cxbladder triage. Essentially, this is a test that uses components of mRNA biomarkers within the urine to generate a score, a probability score that when below a certain threshold says that no further workup is needed.
And when above a certain threshold recommends a physician-directed protocol, which often involves cystoscopy, we found a cohort of patients that had undergone this testing within our system and then matched them to controls based on similar risk indices of having cancer associated with their hematuria, something that we call the KP hematuria risk index. So, just about 3,400 patients of cases were matched with cohorts, and we stratified that cohort based on the results. And if you can see here, the results of that testing really had an impact on the clinical testing that was received downstream from their diagnosis of microscopic hematuria.
Within six months, patients who had undergone triage testing that were deemed low probability by the biomarker rarely underwent cystoscopy. Just under 4% of those patients had a cystoscopy. The patients that were deemed higher risk based on the biomarker were much more likely to undergo cystoscopy than those that were matched the controls that were matched to that group, showing that there was a allocation of cystoscopy to the patients that needed it most based on the biomarker testing. Similarly, we saw some patterns of increased use of CT urogram among higher risk patients and a slightly lower utilization of CT urogram among patients that were deemed low probability of urothelial cancer.
And perhaps most importantly, the impact on cancer detection wasn't negatively affected by this guide to the biomarkers where the patients that were deemed at higher risk actually had a high statistically significant detection of cancer and that there was not a statistically significant difference among the patients that were deemed low probability of having cancer based on the biomarker testing.
And all in all, when you look at the proportion of patients that were deemed higher or low probability, use of this biomarker avoided a number of cystoscopy procedures and CT scans, just about 28% of referrals for hematuria avoided cystoscopy, suggesting that use of this biomarker decreased over-utilization of this invasive test and potentially decreased the burden of radiation, et cetera, associated with CT scans. Certainly we have to look further and beyond in terms of its adoption and see the downstream impacts, but overall, very intriguing for the potential benefit in the real-world use of this biomarker within our system.
Sam Chang: Great presentation in a very succinct way of trying to determine how we would integrate a biomarker in an everyday practice. So, a couple questions to ask. The Kaiser system is well known, or maybe not within practicing urologists, but the Kaiser system for actually more than a decade has been actually one of the leaders in evaluating algorithms for the evaluation of microscopic hematuria. It goes back a long, long ways. And so, being able to have such a large number of patients go through the system and evaluating patients is actually very, very valuable. Can you give us an idea what the SOC or standard of care was for this?
Was that based on the Kaiser guidelines, on AUA guidelines, et cetera? Give us an idea of what that standard of care practice is in your system.
Christopher Filson: Yeah, it's a great point. So, with the rollout of this biomarker, and there's no doubt the integrated health system here within Kaiser offers development of workflows and standardization of care that is a little bit more difficult in other settings, but there wasn't a hard and fast mandate or anything like that requirement of these biomarkers for patients presenting with microscopic hematuria. So, it was actually just became available and disseminated as an option for providers. So, it was really driven still by provider preference or understanding or knowledge of this biomarker.
And to that point, you look at current, the most recent iteration of the AUA guidelines really emphasizes the importance of considering biomarkers for what are now intermediate-risk microscopic hematuria patients versus this study was, or at least this utilization of the biomarker was before those guidelines. And many of these patients were actually lower risk than what would be now considered intermediate-risk. They would be considered low-risk. So, we had a fair number of docs using biomarkers for the lower risk patients, but also intermediate-risk patients and also a few high-risk patients.
We have an interest in looking at, there are some patients who had gross hematuria who refused cystoscopy, wouldn't do the invasive test that we said, "Hey, let's at least get this urine test and maybe we need this additional piece of information to guide decision-making." So, in a long-winded way, I guess we didn't have an established mandate or workflow for patients must get this first before considering cystoscopy, but rather it was on the onus of the provider and their conversation with the patient to offer it as an option for patients who were deemed overall lower risk for having microscopic hematuria associated with the cancer.
Sam Chang: Yeah, which leads to the second question. It was great to see that the safety of the fact that in low-risk, very, very low, the 0.1% of patients actually had a carcinoma with the utilization of the test. And then the fact that there was a higher capture rate or capture rate when using the biomarker. So, then that leads to the third point and/or question. It would be great for us to know what ultimately happens to these patients that we've avoided the cystoscopy, or we avoided the CT urogram or perhaps both.
Are there plans to actually going back retrospectively in a few years at looking at these patients specifically to see if anything is "missed" or that we caught something early? Tell me your thoughts about the next steps regarding the research.
Christopher Filson: Yeah, I think it's important to do so. I think we do want to make sure those gaps are missed. Fortunately, as you mentioned, the incidence of cancer among this patient population in general is low enough that I think we feel comfortable about the safety of this approach. The most exciting things moving forward are going to be understanding its adoption. To your point about workflows and how it's used, who were the physicians that elected to use it and who were the ones that weren't?
And as we get into a guideline that more clearly emphasizes the potential benefit of these biomarkers, can we understand who is on board with it and who may be a little bit old school and say, "Oh, everybody needs their scope and CT urogram." And then in terms of further tests that are being developed and investigated, there's newer urine-based biomarkers like Triage Plus, which some recent evidence came out support that it's even more specific in terms of guiding decision-making so we could even potentially knock the frequency of cystoscopy down even lower, because 2.5% is better than the control group in terms of detection of cancer, but ideally we would have it more like 10% to 20% where we can even shave more cystoscopy procedures off these patients with such a low detection rate.
So, we're looking towards investigating additional biomarkers within our system in the future, and it's exciting to have this environment where it permits that to be done. Yeah.
Sam Chang: So, then the last question, Chris, is how are you going to, at this point within the Kaiser system or say individually, how are you going to triage the Cxbladder triage? Who gets it? Who is going to be that patient? Because initially in this, there was an interpretation by the physicians. Within Kaiser, you can see setting up an algorithm-based system where anybody with microscopic hematuria less than this age is going to get a Cxbladder. Tell me what you envision regarding that.
Christopher Filson: Yeah, I think as a system, we're grateful for the latest iteration of the AUA guidelines because it really crystallizes and provides more clarity of these low, intermediate and high-risk groups and emphasize that that intermediate-risk group is really where I think the money is right now in terms of benefit from the use of these biomarkers. By no means do the guidelines say that that should be first-line. It's more of a discussion between the physician and the patient, and should the patient want cystoscopy, certainly can be pursued.
I would say that we're encouraged by these results and would probably lean a little bit towards more emphasis on the benefit of those biomarkers for intermediate-risk patients moving forward and shift away from its use for the lower risk patients where even as the current guidelines highlight, further testing should really only be limited to a repeat urinalysis down the road rather than any other kind of expensive or advanced testing.
And for the high-risk for now, we're not going to recommend biomarkers except for the case I mentioned where patient adamantly refuses the guideline-concordant workup with cystoscopy and you say you offered as an alternative, I think those are the two groups, the intermediate-risk and then the high-risk that refuse cystoscopy are really the paths that we're going to take and try to make more established within our system with ongoing work.
Sam Chang: Well, huge kudos to you, Chris, and to the caregivers within Kaiser to study this and evaluate this, continuing to attempt to personalize medicine, de-escalate the invasive procedures, focus on those who really may benefit from determining whether or not the next steps should be taken. So, please reach out, look forward to discussing any further follow-up and the next steps as you guys go ahead. And we miss you in the Southeast, man. That's all I got to say.
Christopher Filson: Hopefully, we can catch up soon at SUO or something else in the near future.
Sam Chang: That'd be fantastic, Chris. You take care. Best of you and your family.
Christopher Filson: All right. See you, Sam.