Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of radiologic oncology at M.D. Anderson Cancer Center in Houston, Texas, and we're live in Las Vegas at AUA 2025. It's a pleasure to welcome Professor Kent Mouw and Bogdana Schmidt to our studios. Welcome, Bogdana, Kent.

Kent Mouw: Thanks.

Bogdana Schmidt: Thank you.

Ashish Kamat: So you guys are doing a lot of stuff here at the AUA. One of the things you're doing is taking part in this age-old debate at the IBCG-AUA forum on what's the best treatment option for a patient with muscle-invasive bladder cancer, taking the bladder out or radiating the bladder and leaving it in? So, Bogdana, your take first?

Bogdana Schmidt: I take the bladder out.

Ashish Kamat: Tell us why.

Bogdana Schmidt: Well, I think there are a couple different ways to think about it. Obviously, we're talking about cancer control outcomes. We want to provide a durable response to the patient. We want cancer cure.

From a functional standpoint, we also obviously care about the quality of life of the patient. But I do believe that cystectomy provides a good quality of life for the patient. We just saw at the CISTO study at the plenary today, that quality of life for cystectomy patients, even compared to bladder-sparing treatments, is good. It favors cystectomy.

And I think from a health-care resource utilization standpoint, a lot of patients are done with multiple visits, multiple surveillance, multiple plans and trips that have to revolve around their bladder. And leaving the bladder in doesn't take that away, not just talking about the financial toxicity of it, but just the anxiety and the mental-health aspects as well.

Ashish Kamat: So Bogdana makes a compelling argument, obviously. But Kent, the field of bladder preservation with TMT, for example, has evolved over the years. It's no longer the burn the bladder and leave a crippled bladder in. So share with us your perspective on why you would recommend the bladder-sparing option.

Kent Mouw: Yeah, I think it's an interesting, exciting time for bladder preservation. As we know, there's no prospective data comparing cystectomy to TMT. I think the best, highest-quality retrospective data we have suggests that in carefully selected patients, TMT provides the same cancer-control outcome, arguably as good or better survival outcomes, and allows the patient to keep a bladder if they have a functional bladder to start with.

And so I think for those reasons, for the well-selected patient population, this is an opportunity to keep bladders. Patients want to keep their bladder generally if it works well for them and provide the same level of cancer control.

Ashish Kamat: And you say well-selected patients. And for our audience, could you expand on that? What's the ideal candidate for bladder preservation?

Kent Mouw: Yeah. So I think this is a tricky thing to talk about, because it's—the truth is that many of the prognostic factors that I think we as a TMT community have done a really good job of defining.

Many of those prognostic factors are also prognostic factors in cystectomy cohorts. And so I think TMT in some ways has been painted into this corner of saying unifocal small T2 tumors—that's your TMT population—where, when you take a step back and you look at the data, you realize that many of the poor prognostic factors in TMT cohorts, T3 versus T2, focal CIS, unilateral hydro, these are things that also, if you look carefully at the cystectomy cohorts, are associated with worse outcomes there.

And so I think it's a really nuanced patient-to-patient discussion that's happening, ideally, in the context of a multidisciplinary clinic. And for the carefully selected patient, the best retrospective data that I think exists, published about a year ago, the entry criteria for the comparison between cystectomy and TMT was tumors up to seven centimeters, focal CIS, and unilateral hydro were involved. And so I think it's a little bit more liberal, per se, than I think many of the classic TMT patients are thought to be.

Ashish Kamat: So I don't disagree with you, but I'm going to push back just a little bit. Because, again, the IBCG paper on bladder preservation that both of you are on just came out, and it says exactly what you're talking about—the prognostic and predictive factors.

But let me push back a little bit and say that yes, those are prognostic with cystectomy. But they also help guide who should be getting neoadjuvant or adjuvant therapy in that situation. Share with us how that works in the TMT world.

Because traditionally, or at least from everything that we've seen published, there is not that concept of neoadjuvant therapy and adjuvant therapy after TMT. So enlighten the audience a little bit.

Kent Mouw: Yeah. I mean, I think that in the US, the RTOG trials have generally not used neoadjuvant chemotherapy. Some of them have used adjuvant. However, if you go to the UK, where TMT is much more commonly employed, neoadjuvant chemotherapy is actually the standard there.

And so they're giving their patients neoadjuvant chemotherapy, particularly those with more advanced tumors, hydronephrosis. And then, based on response to neoadjuvant chemotherapy, directing local therapy appropriately. And so if you look at the big randomized trials from the UK, a significant percentage of those patients are actually getting neoadjuvant chemotherapy prior to TMT.

Ashish Kamat: I have a lot to say about UK trials, but let Bogdana speak.

Bogdana Schmidt: I'm just about to punch back a little bit because you mentioned the UK trial. If you look at the FAIR data, it took them, what, 30 months to get 45 patients on trial when they were trying to randomize after neoadjuvant therapy. So it's not necessarily feasible in that way.

If we had that data, I'd feel good about it. But the trial that tried to provide us that data said this is not feasible. And it's not generalizable because patients who were assigned to have one arm then crossed over to the other.

I agree with you. I think the landscape in general is moving towards that sandwich treatment approach—neoadjuvant, bladder-focused adjuvant—because we are clinically understaging these patients.

There's that micrometastatic disease aspect that TMT traditionally, in the way that it was—right, the radiosensitizing chemo and radiation—does not address. And so you worry about those patients recurring out of field but also potentially being undertreated for deeper tumors that maybe are not being recognized by imaging studies.

Ashish Kamat: And everything we do should be patient centric. So the patient should be at the core of all the counseling and decisions we make. One of the things that irks the surgical side of the community is that our rad-onc colleagues don't see the patients in follow-up, and they have hematuria when they have the side effects of radiation, et cetera, et cetera.

Not to put you on the spot, Kent, but how do you account for all the secondary effects of radiation if you don't see the patients back?

Kent Mouw: Oh, I mean, I think in our clinic, I'm seeing these patients every three to six months, up to five years or beyond. And so I mean, I think there is really—in our practice—a multidisciplinary approach to follow-up.

And so they're seeing myself or a medical oncologist every three months. They're seeing the urologist for cysto every three months. And so I think there's multiple levels of eyes on these patients in follow-up and taking care of them for anything that comes up, whether it be disease-related or treatment-related.

Ashish Kamat: So you do your own cystoscopy as well, or?

Kent Mouw: No.

Ashish Kamat: No, it's an honest question.

Kent Mouw: Yeah. Of course, the urologists are central in both, clearly, diagnosis, management, and follow-up in TMT-treated patients. And so I work carefully with them. We coordinate—we're each seeing the patient every three months for the first couple of years for sure.

And so, I mean, the problems that come up in the bladder, clearly we rely on our urologic colleagues to manage those. Thankfully, when you look at long-term data from big cohorts, the late-toxicity rate—grade 3 or 4 GI/GU toxicity—those rates are really low single digits.

The number of patients who need a cystectomy for TMT toxicity is really low in the RTOG and other big cohorts—1%, 2%. And so I think these can be terrible cases. I mean, we rely on your expertise to manage them.

I think big picture we have to remember that, thankfully, those are really rare. These radiation-induced, for instance, second malignancies of the pelvis can be really terrible for patients to manage.

Big picture, we have to realize that those are really, really rare outcomes. And the likelihood of the lifetime risk of dying from a second malignancy is on par with the known toxicities and life risks we take offering patients cystectomy.

And so I think they can be terrible. Everyone's seen these cases. We rely on your expertise to manage them. But I think big picture, the patient-reported quality-of-life data would suggest that patients who keep their bladders are generally as happy in the bladder and bowel domains as patients who have a cystectomy.

Ashish Kamat: I know you're itching to say something.

Bogdana Schmidt: I'm trying. So I agree. I think the catastrophic outcomes—they all stick in our memories because they're horrible. But there are the more common occurrences where you have the urinary frequency, urgency, hematuria. You're trying to get the patient hyperbaric, but you're worried, what if their cancer recurs?

You're trying to maximize them on medications, and then if they have a local recurrence and you're thinking, oh, this isn't muscle invasive anymore, that's great. But then you can't give them BCG, or you can't give them something because their bladders won't tolerate it at that point from a functional standpoint. And that does become burdensome for the patient and for the urologist who is being relied upon to make the patient better, even though they're cured from their bladder cancer, effectively, statistically. But the lifestyle factors, I think, are still challenging.

Kent Mouw: Yeah, and I think that's right. It's incredibly important to have these conversations with patients. And when offered, I think that if you say there are these serious long-term outcomes that can occur—thankfully they're rare—here's an opportunity to keep your bladder.

I think many reasonable patients are going to select TMT. Others are going to select cystectomy. And I think as long as the multidisciplinary team is on board, everyone's weighed in. I think that's the patient-centric part of what we do.

Bogdana Schmidt: And I think that patients really do—there is that little bit of self-fulfillment where if you look at studies across, even for conduits and neobladders and not just outside of urinary diversion, patients are generally happy with what they chose because they made that choice.

And so if they make an informed choice and they were well counseled, most patients will accept that outcome thinking that they knew the risks and they're going to take that outcome as it is. But that doesn't necessarily mean—and—

Kent Mouw: I think that is the argument for multidisciplinary care. You need to have these conversations with patients upfront, lay out the options, lay out what it looks like to have a severe late toxicity with TMT—same thing with cystectomy—and say, here's your options. And what do you think is best suited for your case?

Ashish Kamat: I'm glad both of you wrapped it up by saying that because, ultimately, it is the informed patient making an informed decision that is truly our responsibility. And I'm sure it irks you as much as it irks me when you hear patients coming in saying they were told that either radiation is the work of the devil or the cystectomy is the only way to do it, because that's not true.

They need to get a real perspective, but they also don't want to hear from the radiation oncologist that radiation has absolutely no side effects and “I can treat this, and this will never come back, and you're 40 years old, and the rest of your life is going to be worry free.”

So I think what you said—keeping the patient at the center of the discussion, giving them all the data points to choose from, but then helping them guide and make the right decision—is critical. And having teamwork, because clearly, sometimes we can't do a cystectomy on a patient, and I rely on you to do radiation therapy because they're not a surgical candidate.

And oftentimes you will rely on Dr. Schmidt, for example, to do a salvage cystectomy if the patient has recurrent disease. So it's great to see this teamwork. We'll have you debate on Monday, though.

Kent Mouw: Sounds good. Thank you.