Ashish Kamat: A warm welcome to all of you from the UroToday Studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center in Houston, Texas. And we're live at AUA 2025 in Las Vegas. And it's a distinct pleasure to welcome two distinguished gentlemen to the UroToday Studios, Professor Benjamin Pradere and Josh Meeks. Welcome, gentlemen.

Joshua Meeks: Thank you. Great to be here.

Benjamin Pradere: Thank you.

Ashish Kamat: So there's a lot of stuff happening here at the AUA in bladder cancer. And the reason we're here, of course, is we can talk about what's going on with BCG and especially your role in the AUA-IBCG Forum that's occurring on Monday. So the question is, is BCG today still the king or do we have other options? And Josh, your take.

Joshua Meeks: Yeah, I mean, I think it's really incredibly hard to beat BCG. I mean, I think that's been the challenge for the last 50 years. We have a drug that's really pretty good. And there's very few drugs that are as cheap as it is. It's incredibly accessible for most patients. And when given and given properly, leads to we'd say, anywhere from 60% to 80% response rates at two years.

So I think given it's tolerable, it's cheap, urologists know how to give it. And the biggest thing is when it doesn't work, we know the patient's in trouble. We know that phenotype. So all that comes together as a standard and makes it incredibly hard as the bar to beat that.

Ashish Kamat: And Ben, you have the alternate side, right, so.

Benjamin Pradere: Yeah, I think what Josh just said, when we look at BCG, there are still two parts. The first part is the clinical part where if we want to develop a drug to outperform the oncological outcomes that are already pretty really good. But there is also the safety and the tolerance of BCG that although we know this treatment so well, we don't even sometimes really realize how much it can impact the quality of life in terms of this area and all the systemic effects that are still known.

And on the other part, there are all the logistic parts. We need to have a good surgeon with a good TURBT at the beginning, especially in BCG-naive. We need to have as well a good adherence to maintenance. It's beautiful to see the maintenance therapy in randomized clinical trials or prospective trials.

But real life is much, much harder. And there is also this problem with shortage. Therefore, I believe there is still room for developing new drugs. And this is the exciting part of this year and the next coming years.

Ashish Kamat: So Josh, Ben raises some important points that we've all struggled with. I mean, how do we get patients to tolerate three years? They have these side effects. And our patients tolerate the side effects. And I think we also tolerate the side effects. Any tips or tricks that you use in your clinic to help these patients with BCG instillation?

Joshua Meeks: Yeah, I think the biggest thing again, is using maintenance at reduced dose. I mean, because of the shortage, we've cut our doses to half and to third. And shockingly, I think it's just as efficacious. But also the tolerability is much better.

People don't like to hear reduced dose. They think they're getting an inferior cancer therapy. But really, the tolerability is so much better than what we saw before. So I think that's a huge thing. Obviously, anticholinergics, and then time. Again, giving people time from that TUR. Because a lot of it is still-- when we're doing primary and secondary TURs on patients, their bladders are not well to begin with. So I think that's the biggest thing for most patients.

Ashish Kamat: Yeah, I think that's an important point. Because this thing about needing to start BCG and X weeks after the resection is all based on nothing. And the sooner you start some toxic therapy, the more side effects you're going to get. Benjamin, you talked about other alternatives or other ways to improve on BCG. What are some of those that you are seeing either here at the AUA or EAU just as concluded recently?

Benjamin Pradere: Yeah, so this AUA was the first release of one of the most awaited randomized clinical trials with sasanlimab subcutaneous immunotherapy. And they show a benefit in terms of RFS in this population with T1 and CIS patients. We see a benefit in these patients. So it was a combination of BCG plus sasanlimab.

But there are so many other trials that we are awaiting the results of, especially the ALBAN trial with another immunotherapy with atezolizumab. And as well we have, in the BCG-naive field, the big trial is also the SunRISE-3 trial, combining TAR-200 and cetrelimab or TAR-200 alone. And I think all these studies are really trying to change the field of BCG-naive that was just BCG and that's all. And now, we have the window of opportunity to over-select the patient that will be the best candidates for a new alternative to BCG alone.

And I also think that although we don't have so far the result from the BRIDGE trial, especially in the US where GemDoce is so used, actually much more than in Europe so far, I think GemDoce is also a good alternative. And I believe that the BRIDGE trial that is still enrolling patients will be also interesting to see the results.

Ashish Kamat: Yeah, I mean I think the CREST trial, kudos. Because of a randomized study. We've always seen better outcomes with BCG in more modern eras because we have better technology. We resect the tumors better. We see things better. We counsel patients better. But having a randomized study showing that, yes, BCG was still phenomenally successful, but you can improve upon it slightly.

Josh, not to focus too much on the CREST study. But let's assume you have the CREST or you have some other X you can use with BCG. What's the patient you're thinking at the back of your mind? Here's a patient in front of me for him or her, I want something more than just BCG.

Joshua Meeks: Yeah, as you said, I think there's two things to think about. One is the tumor, and then the other is the patient. So there's certainly tumors that we worry a lot more about. So we worry about progressions of T1s, T1s with CIS, maybe LVI. We don't know about the variant percentage in this study. But those are all patients that we clinically worry about.

And so you'd say, if I could give a little more, this is where I would do that. But then there's a lot of patients where this is their first encounter with cancer. To them, this is life or death. And they want to do absolutely everything they can. When you look at those curves that really separate, this is an addition on top of that.

And so, as surgeons, we see the full spectrum and think, well, a recurrence is not necessarily fatal for most patients. But to that patient, that may be the difference that say, if I could do something more, I would be interested in that. So I'm very interested to start having those discussions with patients. And so I think those are the two things that are going to drive it.

Ashish Kamat: Yeah, I think patient-centered care, shared decision making is very important. Ben, you obviously come from France. We can tell that from your accent, but I know it anyways. But you also have to worry about cost in your health system. Sometimes, here, we tend to forget that. So how would you factor in the cost of all these other agents knowing that BCG is so readily available and cheap? How does that factor into your consideration?

Benjamin Pradere: That's a huge issue right now for us because we are trying to convince the authorities that the new drugs, although they may increase the costs, they really have a benefit, especially, for example, now with the CREST trial, successful trial. But I think the main point is, as Josh said, to try to focus on these specific patients that are very high risk, of course, that will accept also the adverse events that come with immunotherapy. But I believe the main work is to convince the authorities that these patients require another treatment than just a BCG standard of care.

Ashish Kamat: And again, we're talking about BCG or BCG plus something and using the parameters that we have. But clearly, personalized medicine is what we're all aspiring to. I know both of you do a lot of research in that arena. So I'll ask both of you that as a closing statement. What's your sense as to where are we to be able to use, whether it's AI, tissue-based or nomogram-based or others to be able to select which patient can I just use BCG, which patient I need BCG plus something, and which patient I need something completely not even BCG oriented? Josh.

Joshua Meeks: Well, we just got the data today that we have a new drug. So now, we have to go look at the biomarker part of it. And I don't know where that sits. So there's a lot of things. There's urine tumor DNA, there's ctDNA, and then now, AI. So I think all those together, we have to start doing those studies. But the page turned today. So then we can start looking at who does this work better in?

Ashish Kamat: Ben.

Benjamin Pradere: Yeah, definitely. I think ctDNA, urine DNA will be probably a game changer for us. We will see the biomarkers. We also have tumor selection. Probably FGFR might be interesting in some part for some tumors or HER2 as well. But that is still in really early development so far.

Ashish Kamat: So closing statements from you gentlemen. Is BCG still king? Ben.

Benjamin Pradere: It's still the king, but he's in danger right now.

Joshua Meeks: Yeah, I mean, it's I think going to be the backbone of what drives our care for this cancer. And so the question would be, is there another benefit? And we'll just have to see how it turns out.

Ashish Kamat: I couldn't agree more. Thank you, gentlemen. That was always a pleasure.

Benjamin Pradere: It's a pleasure. Thank you very much.

Joshua Meeks: Thanks. Thank you.