Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We are at AUA 2025 in Las Vegas on UroToday. Delighted to be joined, as always, by Dr. Steve Williams, urologic oncologist at UT Galveston. Steve, thanks so much for joining us on UroToday.

Stephen Williams: Well, thank you for having me. It's-- actually, it's always a good time to be with you.

Zachary Klaassen: Always a good time.

Stephen Williams: I mean, we don't have a shortage of laughs.

Zachary Klaassen: No, we don't.

Stephen Williams: Let's just say that.

Zachary Klaassen: And we have a very serious topic today we're going to talk about. We're going to talk about BCG unresponsive CIS. You've done some great real world data analysis, and again, at this meeting at AUA. Just tell us a little bit, before we get into this study, what's the landscape look like currently in 2025?

Stephen Williams: Sure. Well, for one, it's pretty exciting. At the AUA, how many times have you seen down the Las Vegas Strip where there's actual advertising for bladder cancer?

Zachary Klaassen: Yeah.

Stephen Williams: It's the first time, right? And then across the entire meeting, because of all the novel agents that are being developed, particularly in high risk non-muscle invasive bladder cancer, and then more importantly, BCG unresponsive disease. So for myself, doing some research, and really standing on the shoulders of others and our team members, it is a particularly exciting time, but also, too, a moment of pause. As a number of these agents are becoming FDA approved, we're also now going to have to understand how we are prescribing and really what's the true unmet need. And that's where this research hopefully provides real world evidence in the carcinoma in situ disease. And then my colleague has presented on the high grade papillary.

Zachary Klaassen: Awesome. So tell us about the study design, what registry you looked at for this data at AUA.

Stephen Williams: Sure. Well, the first is the data is from 2015 to 2022. And more importantly, also, too, I use a combination of AQUA, the AUA registry, but then also used the Komodo database for the claims.

Zachary Klaassen: Yes.

Stephen Williams: And then merging those, like SEER-Medicare, if you will. But the one thing I love about AQUA is actually we're able to determine carcinoma in situ. And then what we use in our administrative data set is actually the FDA one year of BCG, which is about seven doses of BCG within a year and then any patient that received subsequent chemotherapy within six months following.

Zachary Klaassen: OK.

Stephen Williams: So that was our definition, first off, for the BCG unresponsive population. And then basically what we wanted to do is understand what happens to those patients after that, what type of treatments that they in fact receive, not only intravesical but cystectomies, and so on.

Zachary Klaassen: Sure. Lots of good data that came out of it. I mean, we could-- there's a number of jumping off points, but maybe just give us the highlights of what you guys found.

Stephen Williams: Well, 70%, roughly 71% patients received a chemotherapy within that time frame. And then we looked at a period of up to 24 months.

What was interesting is actually a number of patients received mitomycin, as a single agent.

Zachary Klaassen: Wow.

Stephen Williams: Gemcitabine, docetaxel, which as we know tends to be our salvage regimen, only about 12.5%.

Zachary Klaassen: So more mitomycin than gem doce.

Stephen Williams: Correct.

Zachary Klaassen: Wow.

Stephen Williams: And really, it was triple the amount. And I guess, then I have to put my hat back on in regards-- I had some time in practicing, in private practice.

Zachary Klaassen: Yeah.

Stephen Williams: I think urologists are familiar with BCG. And then they're also familiar with mitomycin, historically. So I guess these data aren't as surprising, but really a stark difference. What was also interesting is about a quarter of patients actually underwent a radical cystectomy within 24 months. And then more importantly, the recurrence that was noted was up to 80% within two years. So really, it was a pretty glaring opportunity, if you will, to where we can address perhaps guideline appropriate treatments of these patients, but then perhaps with some of the novel agents that are coming on board, also supporting why we need some perhaps curtailed regimens that are easily understandable but really serve an unmet need.

Zachary Klaassen: So when we look at this, I mean, I think the cystectomy number is interesting, about 1/4. There's one side that says we can give multiple therapies safely, but the gold standard is still radical cystectomy. Often patients either aren't fit for it or they refuse it. How do you take that 25%, how did you digest that number?

Stephen Williams: Well, for one, I was surprised, to be honest. And we don't know, and it's hypothesis generating work that these patients receive multiple different lines of intravesical therapy. But really, within 24 months, a quarter of patients. I mean, that was quite surprising. And perhaps, a number of these patients obviously ended up having more aggressive disease, to where the primary urologist then was able to refer or perform the surgery, radical cystectomy. But what would be also interesting is as bladder sparing options are becoming increasingly used, particularly in the United States, is also whether or not that was offered, as well, in this particular population.

I think what we need to do is get back to the patient and understand their disease state and then ensure that they're actually getting guideline recommended salvage therapies, which, in an academic medical center, some would argue is gemcitabine, docetaxel would be the preferred option. It's in our guidelines. But then also, too, a number of these newer agents that are coming online, and there are some excellent presentations, at this year's AUA and some other FDA-approved agents coming on the forefront.

Zachary Klaassen: Yeah. I think you're right. I mean, we're going to see in the next year or two FDA approval for more agents. So it's going to be figuring out the sequencing, but not forgetting about cystectomy in those appropriate patients. Maybe those are those T1's we're giving a shot to. They recur quickly and you say, OK, we got to take a stab at the cystectomy at that point.

Stephen Williams: Yeah. And then I mean, honestly, people don't want to lose their bladders. So I think sometimes being a urologist, if you're able to say that you're able to save the bladder, patients believe that.

Zachary Klaassen: Yeah.

Stephen Williams: They trust their urologist, their doctor. But then we got to make sure that when we're doing that, that the physician also, too, understands and having that dialogue so that patients can have earlier treatments if it's in fact a more aggressive disease after receiving BCG, and then not just continuing to instill intravesical agents. And we know historically once you get BCG, mitomycin C, not only is it more costly than gemcitabine, and we also analyze that separately. But really proceeding with guideline recommended therapies.

Zachary Klaassen: Yeah, absolutely. Always a high level discussion, Steve. A couple take home messages for our UroToday listeners?

Stephen Williams: I think let's just try to keep things simple.

Zachary Klaassen: Yeah.

Stephen Williams: As newer agents are coming online, even myself-- and I'm in this area, this field, research, clinically-- I hope we could do better to distill so that anyone, our patients more importantly, can understand which pathways that we need to go on. Another exciting point that I don't want to get into too much is the leveraging artificial intelligence.

Zachary Klaassen: Absolutely.

Stephen Williams: So that we can understand which markers are present, yes or no for all of these agents, so that then we can better provide some salient information to determine which particular novel agent, which are going to be more costly than any of the other intravesicals that we have, historically gemcitabine, docetaxel. But like I said before, and even then, that statement can be a little complex as distilling it to where our patients, our customers, our doctors, and really all of us can better understand how to get our patients on the right treatment and the appropriate treatment that they understand.

Zachary Klaassen: Yeah. Well said. Steve, always great having you on UroToday.

Stephen Williams: Yeah. Thank you for having me.