Mark Tyson: Thank you, Dr. Kamat, for allowing us to present our work here today with you on UroToday. I'm going to be discussing, like you said, our study on evaluating blue-light cystoscopy compared to white-light cystoscopy in patients with non-muscle-invasive bladder cancer. And obviously, your audience needs no real introduction to this, but the clinical rationale for blue light is familiar. It improves visualization of tumors, which can be difficult sometimes to detect under white light, and particularly those carcinoma in situ or flat lesions. But the question we wanted to address here today was more of a value question. If blue-light cystoscopy detects more disease, does that lead to more downstream care, more procedures, and ultimately higher costs? Or does it improve cancer-directed management without meaningfully increasing the economic burden?
And so, to evaluate that, we used a large real-world claims dataset. We compared matched blue-light and white-light cystoscopy cohorts. It was a retrospective study using the Optum research database, and we started with more than 95,000 patients who had both cystoscopy and bladder cancer claims. And then, we identified patients undergoing blue-light cystoscopy, and then, matched them to the white-light participants. The final analytic cohort was 794 blue-light patients and 4,764 white-light patients using a one-to-six match. So, patients were matched based upon index year and by the time interval between their bladder cancer diagnosis and cystoscopy. We then used inverse probability treatment weighting to further adjust for a whole host of baseline differences, including demographics, comorbidity, prior utilization, and costs in bladder cancer-related care. The cohort was typical, I think, for non-muscle-invasive bladder cancer, mostly older people, median age of 73, and predominantly male.
And interestingly, after weighting, CIS claims during the study period were substantially higher in the blue-light group, 18% compared to 9% in the white-light group with the P value shown there, which is of course entirely consistent with the known advantage of blue-light cystoscopy in identifying CIS. But a very interesting sort of parenthetical note there is that even our IPTW models, these treatment models, many of them have a very difficult time controlling for all of the factors that go into treatment selection. So, just a word of caution when you're looking at these types of models.
So, the next question then, what does that detection signal mean downstream? Does it increase cost? Does it translate to more care? And this slide captures that main value finding. After weighting, blue-light cystoscopy was associated with more bladder cancer ambulatory care, specifically that bladder cancer-related ambulatory visits were 1.3 visits per month per patient in the blue-light group compared with one per patient per month in the white-light group. P value there is significant. And this observation, I think makes sense clinically. If blue-light cystoscopy detects more CIS, this leads to more cancer-related surveillance, intravesical therapy, related management, et cetera.
But importantly, that increase was specific to bladder cancer-related care as all-cause ambulatory utilization was not significantly different. And so, the cause, I think are the key point here though, that figure on the right, all-cause total medical and pharmacy costs were not significantly different, about 2,988 versus 2,886 per patient per month with a P value shown there not significant. And bladder cancer-related costs similarly were not significant. So, I think the interpretation here at a very high level is that blue-light cystoscopy appears to increase cancer-directed care intensity, but likely because it detects more CIS, more significant disease, et cetera, but that does not translate into a statistically significant increase in total or disease-specific costs.
And I think this could be due to a couple of things. First, I think utilization with blue light is ambulatory, obviously, and bladder cancer-specific. And this does not generally increase in more inpatient or emergency care per se, which are typically high-cost settings. But even more than that, I think better detection leads to more efficient cancer care. It identifies patients with CIS or clinically-important disease earlier, which allows more appropriate treatment decisions upfront. I think potentially reducing missed lesions, repeat evaluations, delayed escalation, et cetera. So, I think that the care itself becomes more cancer-directed, but not necessarily more expensive. And that to me, I think is the key value message here. So, with that, I'll stop and take any questions.
Ashish Kamat: Thank you so much, Dr. Tyson. Blue light's been around forever, and you and I use it in our clinical practice, and I don't use it in everybody, but I use it appropriately as I'm sure you do. And then, we hear from folks that it might increase the cost burden for the system, for society. I think there's a lot of other things that are priced completely unreasonably. Blue-light cystoscopy is actually very reasonably priced. And then, when you have data such as you are showing that it truly does not add the economic burden to the healthcare system, my next logical question to you is, can you think of any reason cost-wise why someone would actually, in today's day and age, say, "I'm not going to adopt blue-light cystoscopy in my clinical practice"?
Mark Tyson: I really can't. I mean, I think if you're in a really small system and acquiring the equipment is a big capital outlay, I could see how that could be a challenge, although I think this equipment can be rented. But I think there are situations where that capital outlay would obviously just be insurmountable. But generally speaking, it's so good for patients that I think it's worth the investment. But yes, I mean, we obviously, both of us practice in big healthcare systems, and it's very resource-rich. So, I want to be sensitive to that, but generally speaking, I think if the investment can be made, it's worth making.
Ashish Kamat: And one thing that you didn't specifically look at, but you alluded to a little bit is the whole issue of the CIS, the CIS, the papillary, the incident. And that's something that the FDA, of course, has been very interested in. All the clinical studies for registration purposes look at CIS itself as the endpoint. Looking at the blue light penetrance, and again, looking at your dataset, maybe not the endpoint of your particular study, how do you think the adoption of blue light economically, practically, will affect this whole BCG-unresponsive disease space moving forward?
Mark Tyson: I'm so glad you asked. I looked at this recently. We're publishing some data and I think that the... I had two patients in this last week that were going to come to mind where we resected a third of their bladder because we saw a lot of CIS, and maybe you could make the argument that you don't need to resect all the CIS, but I did because I didn't know what it was, and it was blue-light positive, and it came back as CIS in both patients. And I just think that those patients are going to do better long-term, whatever intravesical therapy we put on having treated their entire disease burden with a TURBT.
And I will tell you, sometimes in the back of my mind, I wonder if many of these response rates that we're seeing in these BCG-unresponsive trials are not because we're getting better at TURBT. We're more focused on it, we're more systematic. There's been a couple trials recently published on quality in this space, ERAS in this space. We're just getting better at it, and so, blue light makes us even better at it. And so, I think that sometimes we could be conflating treatment effect from a drug with a really good TURBT in a single-arm phase-two design. So, I think that it's really hard to tease that out, but I think this is a really pivotal piece to good outcomes in the BCG-unresponsive population.
Ashish Kamat: And then, one thing, Mark, it's been a pet peeve of mine now for more than going on three decades that we don't focus as much effort on training people in a high-quality TURBT as we do on the [inaudible 00:09:17] gimmick when it comes to robotic single port or something like that.
Mark Tyson: Yeah. Absolutely.
Ashish Kamat: But every patient that walks through a bladder cancer clinic will at some point get a TURBT, and hopefully, the number of patients needing a cystectomy is literally one fifth of that. So, one of the things that we've done at the IBCG, and your part of it, of course, is focus on the quality of TURBT. We're going to be talking about it this year. UroToday is going to be covering it. You are an integral part of it. But looking forward to what we might be discussing and your current data on the cost, just in closing, what would you share with the audience about the role, the cost, the pros and cons of blue light, optical enhanced technology, just call it that, in high-quality care of patients starting with TURBT?
Mark Tyson: I think for patients where you're worried about CIS, so flat erythematous lesions or positive cytology, I think blue light is paramount. Like you said earlier, I'm not sure that you need to use it in everybody. I think in that patient population, the really high risk, you're worried about CIS, I think it's really valuable and I think it's really critical to a good long-term outcome. I think they're going to cycle through less of these intravesical therapies if they have a good TURBT at baseline.
Ashish Kamat: Great. As always, Dr. Tyson, a pleasure having you and see you soon.
Mark Tyson: Thank you, Dr. Kamat. I appreciate it.