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Ashish Kamat: Hello, everybody, and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center, and it's a pleasure to welcome to our forum three renowned experts in the field of bladder cancer who are joining us today as a follow-up to the very exciting debate that they had during the rapid-fire session at EAU, which just concluded.

So Benjamin, Marco, Fredrik, welcome.

Fredrik Liedberg: Thank you.

Benjamin Pradere: Thank you very much.

Marco Moschini: Thank you.

Ashish Kamat: So for the audience, we'll have a link to the coverage of the EAU debate. But essentially, the topic that we were talking about was TURBT. And clearly, TURBT is one of those techniques that has fallen off almost like an orphan technique. And there's not as much importance paid to it when it comes to meetings and training programs, et cetera.

Here, during the debate, we tackled a question that often comes up, which is when a patient has muscle-invasive bladder cancer, is a biopsy enough? Or do we need to do a TURBT? And if you do a TURBT, how extensive should it be? So Benjamin, let me turn to you first. You have a patient that comes to your clinic, and you look at the imaging and the MRI suggests-- let's assume you get an MRI-- that it is muscle-invasive. How do you counsel the patient as to what you're going to do next, biopsy, TURBT, et cetera?

Benjamin Pradere: Yeah, thank you, Ashish. Yes, I guess when you have a patient that is coming to our consultation, we always recommend him to explain that TURBT is the first treatment of any bladder cancer. Even if we see that there are, for example, a PI-RADS 5 on the MRI, I think counseling to go into the bladder and performing a TURBT is a really important point because it's the first treatment of the disease. Although, afterwards we will discuss potentially, do we have to be radical and do a complete TURBT or not? In my opinion, the first time is to explain that this is the first step of the disease management.

Ashish Kamat: Yeah, I agree because we're seeing data coming out suggesting that you can avoid a TURBT entirely and just use MRI and go to radiation therapy, for example. But I think the TURBT gives you enough information that it's really useful. Fredrik, let's say you take this patient to the operating room. You look in, and to you it looks clearly like it's going to be muscle-invasive. What are you thinking, and how are you planning your procedure, your TURBT?

Fredrik Liedberg: There are some considerations to be made before you get into the operating theater. So the patient obviously determines at some part the strategy during the transurethral resection. But if it's a generally fit patient and we consider giving him combined treatment afterward with neoadjuvant chemotherapy and a radical cystectomy or chemoradiotherapy. It's important to know if the patient has preferences prior to going into the operating theater because that affects how we plan our transurethral resection.

But there are some indications that doing a radical transurethral resection up front might have benefits. And those are on the side of the seesaw, arguing in favor of doing it radically at first when you go into the operating theater. So that was not an answer, but there are benefits, and the patient preferences and the tumor characteristics influence those while making up your mind how to handle the transurethral resection.

Ashish Kamat: Now, let's assume that this particular patient, Fredrik, has told you in the office that they're not sure whether they want to have a radical cystectomy or do trimodal therapy, et cetera. And they're fit. Let's make them a fit patient that you want to do curative intent. Are you approaching these with a more in-depth TUR, or are you first going and doing a TUR, getting information. And then if the patient wants something in the future, will you come back? How are you planning that?

Fredrik Liedberg: Now, yes, that's easy to answer your question now because now you're narrowing in. We're keeping all options open. And if you don't know, the patient has no preferences, I think it's best to go for a radical transurethral resection because then you have all options. There are other benefits of doing that. Doing just a partial or a biopsy clearly increases the risk of bleeding while awaiting the path report, and so on. So that might get you into trouble.

If the patient develops comorbidities or already have comorbidities that it turns out the radical cystectomy is not an option and you're going for bladder sparing with radiotherapy, chemoradiotherapy, it's good to do the radical resection upfront because then it's open to do trimodal therapy if it turns out to be the treatment of choice. So the answer is, yes, I would go for a radical in this more uncertain setting that you describe.

Ashish Kamat: And Marco, I know we give people different sides during the debate. So tell us a little bit the flip side. And then also tell us what you would actually do.

Marco Moschini: Yeah, so the flip side could be that actually-- so the EAU was defending the fact of not completing the TURBT. And then I show actually that if you consider to offer radical cystectomy to the patient, there are data out there showing you that actually there is no benefit in completing the resection because if your plan is to go through radical cystectomy, you can just get trouble having complications like perforation if you just try to cut too deep.

And on the other hand, if you are considering trimodal therapy, it's the same because actually there is very good survival outcomes for patients treated with trimodal therapy. But for the patient with a low tumor burden, with small tumor and not extensive carcinoma in situ, no multifocal tumor. So if you are doing a radical cystectomy seeing a patient with an advanced tumor, you probably are not able anyway to do a complete resection and then to put on the table a trimodal therapy, hoping to have a similar outcome that a radical cystectomy.

And another point that should be discussed, I think, is the eventuality that you have in your center, a trial, and where it could be important to have a complete resection before starting a neoadjuvant immunotherapy or a neoadjuvant chemotherapy because then you might want to try to assess the complete response after the therapy. In this setting, I think it might be important, but this is a very specific case, a very narrow case. I would say that in general if you are going to offer, as many centers are doing, a radical cystectomy for a bulk invasive tumor, you don't need to complete the transurethral resection.

Ashish Kamat: So that's obviously an interesting perspective that you put forward. So let me ask you, Benjamin, in the era where we have probably better neoadjuvant therapies, right, we have the NIAGARA protocol now with GemCis and Durva, maybe EV-pembro will come into the neoadjuvant paradigm. Is your thought process to do a more complete-- let's leave aside a radical TURBT, but let's just say as much as feasible safely. Is that the thought process still? Or are you now thinking that these better systemic drugs might replace the expertise of the surgeon in doing a good TURBT?

Benjamin Pradere: Well, it's a good question. I believe still that TURBT is a really important point. Most of our studies are looking at complete response rate, and we all know that a complete TURBT will improve the complete response rate regardless of what we do. We see that when we give a neoadjuvant chemo on an incomplete TURBT you see this necrosis into the bladder when you do a cystoscopy just after that. But I believe that giving the chance to the systemic therapy to give its best to a bulky tumor, especially when it's a big tumor, is still really necessary in my opinion.

We have, of course, the study from Galsky showing that just systemic therapy might be beneficial in some patients that are still selected at the beginning. So I would say that if we see that as a clinical practice, it's still very important to think about the complete response rate of this patient and to improve it or to help the systemic treatment, that will also have a really important effect on micrometastasis, on the systemic part and on the local part, on the bladder layers. I think it's still important for me to give a big chance with TURBT.

Although, we have some data from, for example, SunRISe-4, where we have seen, interestingly, but it was very primary preliminary data, that patients with incomplete TURBT, where the TAR-200 was inserted, had better complete response rate when there are still a bit of tumor inside the bladder with cetrelimab in combination with TAR-200. So maybe some discussion still in the future regarding how radical we can be, but I believe that at least to have a clean bladder, for the patient as well, to reduce the number of adverse events in the future, hematuria, overactive bladder, I think, to give him a clean bladder remains important.

Ashish Kamat: Yeah, and just for the audience, TAR-200 is an intravesical gemcitabine-releasing device that is currently being studied in these settings. Fredrik, one of the things that was brought about during our discussion and, of course, on the plenary, was this concept of doing a radical TUR. And then your patient sits and tells you in the office, oh, Dr. Liedberg, you are a phenomenal surgeon. You took out all my cancer. And now, there's no more cancer left in my bladder. How do you counsel those patients in the meaning of a complete cure and whether they should still proceed with definitive radical surgery or trimodal therapy? Slightly different question, but I want to put you on the spot.

Fredrik Liedberg: Well, it's not very common, at least in my Swedish context. But I think it's not uncommon globally, and especially not in the US. It's like a thought for food, that the long-term Harry Herr series was, again, published one or two weeks ago, where he did a radical TURBT and then an open partial. And he clearly shows 3 out of 4 are long-term survivors with the bladders left in place. So there is an option.

The question is how to tailor that particular patient's wish to keep the bladder in place. There are different ways to follow. And as you mentioned, this new systemic, slightly improved therapies and combinations might be an additional gain on top of this. And this is shown in the two recent series, of which Benjamin referred, one the Galsky trial. And I think it depends so much on the patient and the tumor.

So I have difficulties to give you a straight answer. But if the patient decides not to have a cystectomy, you could offer chemoradio. You could do a re-TURBT and evaluate. And depending on these-- the outcome of re-TURBT have a new discussion with the patient. So it's lots of tentative facts that has to be balanced into the wish of the patient. So difficult question. Hard to tell out of-- no, you would need the patient and the bladder and the cystoscopy to have a more straight discussion, I think.

Ashish Kamat: No, absolutely. I think that point is very important. It has to be patient-centric and personalized to the particular situation. And in fact, the IBCG retreat that we had to talk about bladder sparing options, and the publication should be coming out in a week or two, that was one of the things that we discussed in depth in there, right? The radical TUR is clearly related to the patient's journey and what they would want to do next. And sparing the bladder, clearly, in today's day and age is still done within the context of a clinical trial.

We could talk about this forever, but we don't have all that time. So in closing, let me give each one of you the option to provide our audience with a take-home message. And here, remember, our audience is listening to you as the expert. Should we be doing radical TUR or maximal TUR-- let's not use the word radical in a patient that presents with muscle-invasive disease, fit, healthy, sitting in front of you in the office. And let me start with you, Marco. And then we'll go to you, Fredrik. And then I'll end up with Benjamin. Marco?

Marco Moschini: So my opinion is that as a urologist treating bladder cancer you need to know what are the options that you have in your hospital. You need to know what are the patient preferences. But also something which is very understudied, you need to know how is the TURBT performed? So you need to record your outcomes. But also, you need to write on the surgical report exactly what you did in terms of completeness. And in my opinion, very few cases really deserve a complete TURBT. But still, there are cases, like those that we mentioned, trimodal therapy trials, who require complete TURBT.

Ashish Kamat: Fredrik?

Fredrik Liedberg: Well, basically, I agree with Marco. But let's say we have a slightly older patient and there are concerns that the patient is fit for a radical cystectomy and especially those not fit for treating the micrometastatic disease by neoadjuvant chemotherapy. I think it's wise to go for a radical transurethral resection. And I think it's fair that some of these advanced cases should be selected for certain centers doing the TURBTs. They should be done by urologists dealing with uro-oncology and also having the perspective of performing a later radical cystectomy or radiation therapy.

Ashish Kamat: Great point. And Benjamin, final closing words from you?

Benjamin Pradere: Yeah, I can't agree more with my dear colleagues. And I think let's focus on the patient. Share with him before the TURBT according to our imaging. Remains very focused on the tumor characteristics. And I believe that you have to know the sparing strategy conditions, what are the indications, and if you are able to improve the potential options for these patients, to provide him afterwards a good bladder-sparing strategy. It's important to go for radical TURBT, but we remain very clear that we need to really adapt the surgery to the patient and to its tumor.

Ashish Kamat: Absolutely. Great messages. And I want to just emphasize for the audience that our experts are saying that a maximal TURBT should be tailored to the patient. And if you're not doing a maximal TURBT, it should not be because you're trying to take a shortcut but because you think that a nonmaximal TURBT is appropriate for that particular patient in that particular situation. Gentlemen, thank you very much for taking the time. This was a great discussion. See you soon.

Benjamin Pradere: Thank you very much, Ashish.

Fredrik Liedberg: Thank you.