Zachary Klaassen: Hi, my name is Zach Klaassen are in Cartagena, Colombia for the SCU 2025 annual meeting, and I'm delighted to be joined on UroToday for a discussion with Dr. Ricardo Rendon, who is a urological oncologist at Dalhousie University in Nova Scotia, Canada. We're going to be talking today about stage-based treatment for non-muscle invasive bladder cancer. Ricardo, thanks for your time during a busy congress joining us on UroToday.

Ricardo Rendon: Thank you, Zach, for the invitation. A pleasure to be here.

Zachary Klaassen: Now, we could talk for probably half a day about this topic, but we're going to cut it down into a couple of disease states. We've seen a plethora of data over the last several years for non-muscle invasive bladder cancer. Let's just start with the BCG unresponsive disease space. That really was the one that got the ball rolling. What data and what agents have you been excited about that's come out over the last, say, several years?

Ricardo Rendon: So as you said, we could talk about this forever and there is no enough memory, I think, of any of us to be able to ad-lib talk about this, but it's very exciting. Like any other disease space, we usually start treatment with more advanced disease, and as things are working better, we start to move earlier and earlier. So we'll talk a bit later about those. But start with non-muscle invasive bladder cancer that is unresponsive to BCG. So there's a great unmet need between an intravesical treatment to big treatment like a radical cystectomy. So there are a lot of people working hard on this, not just for now, but for many years, just as we had with prostate cancer, there were several negative trials because it's a difficult disease to treat. But now we're starting to have a good trial.

So the first thing that had to happen is the FDA, together with some uro-oncologists in particular, to try to define what the end point should be, what the inclusion criteria should be for all these trials so we're all talking about the same type of patients. And then we're using different treatment approaches. We're using some systemic immune therapy. There are some alone clinical trials or in combination with BCG. We can talk about that in a second. There is also some repurposing of some different administrations of some chemotherapy like mitomycin C in gel or applying gemcitabine in the pretzel device that Johnson & Johnson has, or different methods. Then there is also the viral therapy that we're starting to see, and then there's also the non-viral vectors, and there's different combinations also of BCG. So for now, what we're doing, at least in my clinic for those patients, up until all these trials, now all my patients are in a clinical trial now, but up until now I was using gemcitabine/docetaxel intravesical.

Gemcitabine/docetaxel sounds like a good treatment, but it actually uses a lot of resources. Remember that these patients have to be at an infusion site somewhere for an hour and a half for their gemcitabine administration and then empty the bladder and the docetaxel. So it is a costly time consuming treatment. So it's not just the toxicity to the patient but the financial toxicity. So we have to keep that in mind when we talk about these treatments. So as I said, there were many different negative trials, but now we're starting to have positive trials. And as we know, there's many that are having pretty good three-month recurrence rates, and we weren't seeing very good long-term responses, which is what we would want, but we're starting to see great responses around 50 to 60% at one year. There's one study showing two years the best response.

I think at the end of the day, they're all about 50 to 60%. Whoever cracks the 70% is probably going to be the winner. For now we seem to see that the sasanlimab BCG treatment seems to have a really good response for now, but the concern as a uro-oncologist or in general urology is having that access to planning cystoscopies, intravesical therapy, and systemic therapy. Coordination of care with medical oncology, at least in a country like Canada, where resources are a little more limited, that coordination becomes a big problem because medical oncologists are busy treating their more advanced disease.

Zachary Klaassen: No, it's a great summary. I think the one thing I always look at too is we always have to keep cystectomy on the table, but we know these patients either aren't fit, they know about all these other options, they refuse cystectomy. So I think more data in this space is going to be fantastic. And you alluded to sasanlimab plus BCG, the first time we've seen anything added to BCG in this BCG-naive high-risk cohort. Maybe just talk about potential impact. You talked a little bit about coordination with medical oncology. What do you think the uptake in general will be of this combination therapy?

Ricardo Rendon: So right now those are the best results we've seen, but there are many other coming up. I'm hoping as a uro-oncologist or as a urologist that we'll be able to find a therapy that is intravesical only that can give us similar results. It will be a lot better for most of our systems to avoid that combination of care. At the end of the day, for this very complex patients, even if we had to give immunotherapy in combination, that is going to be much better than cystectomies for many of our patients. And when we talk about financial toxicity of some of these new drugs, what we have to remember is cystectomy is a big procedure that also not toxic for the patient, but is toxic financially to the system.

Zachary Klaassen: Yeah, I think it's a great point. As I start to parse through the CREST data, I think it's that T1 high volume patient where a cystectomy not healthy, or maybe there's a subset of patients we'll use it on. But I think to your point, the logistics of it for everybody who's got high-risk disease is going to be difficult. You mentioned at the beginning, I like the segue as well, everything starts in the really advanced stage. Here we're talking about BCG unresponsive and trickles their way down. The intermediate risk stage has really started to have some data come out in the last little bit, because it's kind of been a gray zone, whether we give treatment, whether we just do cystos. Talk about some of the exciting data in that disease space.

Ricardo Rendon: So one of the things... So I'd like to bring this back a bit. So it has been shown in all jurisdictions in the world that the management of non-muscle invasive bladder cancer is not great. So many docs are not following the stage-based approach. So even if we were able to get our treating physicians to adhere to our regional guidelines and treat patients as they should be, for particularly high-risk bladder cancer patients is a lethal disease, and I think we should do better at educating more physicians to follow this. The second thing is, yes, there are as many treatment options now for patients with T1 high-grade with or without CIS, with or without BCG, and there is also treatments for intermediate-risk disease.

So for the higher-grade treatments, similar to what I was saying earlier, we have really good treatments with viral and non-viral vector therapies, and with other treatment like cretostimogene or nadofaragene, and with the TAR-200 device with gemcitabine, and there's mitomycin in gel. So we're starting to see really good results in that and we're going to have within a couple of years, because as you know, the endpoints for these trials is very quick. It happens within a year. So I'm pretty sure within a couple of years we're going to have a clear winner, I hope, for this. And now we're also seeing intermediate-risk disease. It's not that common disease because they tend to be low-grade that are recurrent. And not only we're looking at prevention of recurrence, but we are looking now at ablation therapies with tumors present. And that's where we're seeing really good, really exciting data with several treatments.

Zachary Klaassen: Yeah, I think the thing I get excited about the intermediate stage is because you have these patients, they're comorbid, they do multiple TURs every couple of years, the ablation and not having to put these patients to sleep for something like a UGN-102 is really attractive I think for those patients that just are persistently recurrent, but never going to necessarily progress to a different stage.

Ricardo Rendon: And not just that, but also you feel bad taking a bladder out for a low-grade bladder cancer. Some of them have tons of disease. There's not much more you can do. But yeah, it is going to be great for those patients. Not too many of those patients, that's right, the very recurrent TA low grade, but we all have those patients in our practice and they are a problem, absolutely, for our practice.

Zachary Klaassen: Ricardo, great conversation. We covered a lot of territory. Anything we didn't hit on you want to share with our listeners? Any take home points for today?

Ricardo Rendon: Just like anything in medicine, things are getting more personalized, but they're getting more difficult to treat, it requires staying on your toes, reading more, going to more meetings, and trying to keep up. I think centralization of care for these complex patients is important. There's plenty of work for everyone, but complex patients probably deserve... And then including patients in clinical trials, things are happening very rapidly, very exciting new treatments and diagnostic tools. So I would encourage people to send patients to clinical trials.

Zachary Klaassen: Awesome. Great summary and thanks for joining us on UroToday.

Ricardo Rendon: Thank you, Zach. Thank you very much.