Dr Bernadett Szabados – University College London Hospital, London, UK
Dr Alexandra Masson-Lecomte – Hôpital Henri Mondor, Créteil, France
Dr Giuseppe Simone – Regina Elena National Cancer Institute, Rome, Italy
Dr Félix Guerrero-Ramos – Hospital Universitario 12 de Octubre, Madrid, Spain
BS: Hi everybody, my name is Bernadett Szabados, I’m a urologist in London, United Kingdom. I’m really glad to be here at EAU 2025 at this discussion hosted by ecancer and I’m especially glad to be surrounded by my colleagues.
GS: Hi, I’m Giuseppe Simone, a urologist at Regina Elena National Cancer Institute in Rome, Italy.
FGR: Hi Bernadett, Félix Guerrero-Ramos, coordinator of the uro-oncology unit at Hospital Universitario 12 de Octubre in Madrid, Spain.
AML: And hello everyone, I’m Alexandra Masson-Lecomte, I’m Professor of Urology in Saint-Louis Hospital in Paris and part of the NMIBC and EORTC Guidelines Panel.
BS: Amazing. So we have seen lots of interesting new data at this year’s conference but I wanted to start off at the beginning. So, intermediate risk bladder cancer – what has changed? Are there any new treatments?
GS: So it’s the largest population of bladder cancer and there is a lot of interest in this specific cohort. What is very interesting is the incidence of the FGF receptor mutation that has been found to be close to 75%. So it means that three patients out of four have a specific mutation that we can target with a specific treatment and these are big practice-changing new and we need to face how to manage a wide population, it’s a lot of people, and we are looking at clinical trials to understand which data are coming, to understand how to treat patients.
BS: So really personalised cancer care is coming down into a really wide patient population. Are there any new treatments that can be applied? Are there intravesical devices in clinical trials?
GS: Yes, we have now intravesical devices releasing drugs and there is evidence supporting that this kind of treatment delivery is at least more durable than what we used as intravesical installation. So we have evidence supporting more or less 96 hours’ persistence of drug release direct into the bladder wall compared to the conventional intravesical delivery with a urethral catheter. So this is a new way of delivering the treatment and potentially impacting on more effectiveness of drugs.
BS: So further on from devices in clinical trials there are also more conventional chemotherapies such as gemcitabine and docetaxel, especially used in the US but also more and more in Europe. Felix, can you tell us a little bit about that?
FGR: Really gemcitabine/docetaxel has really different results. There are contradictory results in some abstracts that we have seen presented at EAU. There are studies on the intermediate risk population, there are studies on high risk, on Ta high grade only patients with different approaches and different results. Some of them say BCG is better, some of them say gemcitabine is better, but I think we have to wait until we have prospective data and in this regard the BRIDGE trial, which is comparing BCG versus gemcitabine/ docetaxel in the high risk population, will make some light on this and maybe will have the last word.
BS: Alexandra, you are using it yourself in your daily clinical practice. What patient population do you treat?
AML: Yes, absolutely. I think what we’ve been discussing at the beginning here is very important. So we’re now in a situation where we’re getting plenty of new treatments, both in the intermediate-risk situation and the high-risk population where we’ll go afterwards. As we have seen, there are a lot of data on different kinds of treatments – GemDoce, BCG, intravesical devices. You mentioned the intravesical devices, I think there is a particularly important study that is called PENELOPE, before I discuss my experience with GemDoce. Maybe for the audience it would be interesting to know exactly what it is about.
FGR: Yes, the PENELOPE study is showing the persistence of the drug inside the bladder and they are showing that if you put the drug inside the bladder with an intravesical device like TAR-200, gemcitabine stays for more time in the bladder, which makes sense because you are putting a sustained release device inside the bladder. So these potentially will translate into better clinical efficacy. We don’t have still definitive results on this but the trials that are being done with TAR-200 are showing promising results so this looks like the persistence of the drug in the bladder translates into a clinical relevance.
AML: Yes, I was really surprised when I read the abstract to see that gemcitabine, just an installation…
FGR: Like a classical one.
AML: Three hours afterwards the drug disappears from the bladder which, as urologists, probably is not really intuitive because when you look at the bladder following the patients the bladder is still red most of the time, but actually the drug has been out for a very long time. And you said FGFR3 mutations are very high, do you think we will have the same with TAR-210? Will it stay also, the fact that it’s an intravesical device that it will be more efficient than just giving the drug?
FGR: Yes, I think it does not depend on the drug, it rather depends on the device. If you are using a way for sustained delivery of the drug, no matter if you put gemcitabine, erdafitinib, mitomycin, whatever you want to put inside the device will warrant that you will have more exposure to the drug, longer exposure. I’m sure if they do this or if they try this with erdafitinib, conventional installation of erdafitinib which, to my knowledge, does not exist but if they compare that with TAR-210 for sure you will have more exposure with TAR-210.
BS: And what about the depth of penetration within the urothelial? It must potentially go through.
GS: Yes, there is. The deeper the penetration, the more effectiveness also in the detrusor muscle, for instance. So we have ongoing trials not only on intermediate risk but we are already working on muscle invasive disease and there are trials.
AML: The SunRISe-4 trial.
GS: For instance, yes. So it’s very important to measure and to be able to understand how deep is the penetration of the drug, how long it’s sustained. This is also highlighting what we did in the past thirty years, doing a simple installation, yes, it’s disappointing.
FGR: Yes, in fact in the very early trials of TAR-200 in mice they demonstrated that the penetration of the drug went further from the mucosa, or the lamina propria, even into the muscle. I think there was some… I don’t know if this was published but there was some evidence that even in these mice not finding drug but finding inflammation in the local lymph nodes after putting the device inside.
AML: [?? 7:25] I didn’t answer your question at all, I just came back to what the gentlemen were talking about. You were asking me about the GemDoce and using it. In my particular experience I’m only using GemDoce in the setting of patients with BCG refractory disease. Obviously if there is no clinical trial, if I have a clinical trial in my institution I will include the patients but, as you know, all the patients cannot go into a clinical trial. So this is where I’m using it the most for patients with BCG refractory that do not want to undergo radical cystectomy but it is true that I also sometimes use it in intermediate risk patients that do recur after having mitomycin installations and recur again, those are the kinds of patients for whom you’re going to do active surveillance but also at some points you go back to TURBT only, you want to go to a new set of installations, sometimes I use GemDoce. It’s true that literature that was the abstracts that were published in this congress are quite confusing for our urologists and for the reader because we see some abstracts saying that GemDoce is performing better than BCG, some that BCG is performing better. I think the main message here is that those are retrospective studies that probably the populations of patients that were treated with one treatment or the other are not the same. There were choices made by the urologist to go for one or the other that probably biased the results. Until we have a randomised study between those old treatments, that will never happen probably, it will be difficult to know exactly what to do. In this setting of patients the rate of progression is really low so it’s also a way to know that we can sequence the drugs and go with one and then after another.
BS: Okay, thank you.
FGR: Before we move on, can I ask you a question? You said you use GemDoce in some intermediate risk patients after mitomycin failure, do you use it before BCG or do you use it if there is an intermediate risk patient mitomycin then intermediate risk recurrence do you go for BCG and then intermediate risk recurrence GemDoce? Or you put GemDoce before BCG?
AML: That’s a really good question. So at the time being I include the patients in MoonRISe -1 actually, so I test them for FGFR3 mutations, those recurring patients.
FGR: And soon in MoonRISe-2 to do an ablative approach?
AML: No, absolutely. So at the time being we test the patients, if they have FGFR3 mutated they will go to MoonRISe. If they are not I try to spare BCG the more I can because what I don’t want to get is a BCG refractory patient too early because sometimes you feel that the patient is refractory to BCG but that doesn’t really mean that the patient has a very aggressive disease, it’s just that it’s recurring again and again whatever you are giving in the bladder. So I try to spare the BCG for the end of the treatment and go to mitomycin and GemDoce and then BCG if it’s needed.
BS: Now that we are talking about BCG I just wanted to get us back to the BCG naïve space. Félix, what’s new in that space?
FGR: Well not big news in this space but promising news now and for the future. Last year at EAU in Paris we presented our preliminary results of the BladderGATE which is a one-arm trial of atezolizumab intravenously plus BCG and we found over 80% of high grade bladder recurrence free survival. This year we’re presenting at EAU a biomarker study which I think is important because these drugs, these systemic drugs, are not exempt of toxicity and also financial toxicity because of their price. So there might be a way to try to select the patients and find the best candidates for these drugs. So in our study this year we present biomarkers of response to atezolizumab plus BCG which, of course, should be validated by external cohorts. I think it’s a good way to start to find biomarkers and do some kind of personalised medicine. Also relevant now because we have the positive press release, we don’t know any data yet but we have a press release from the CREST trial where they state that subcutaneous sasanlimab plus BCG induction and maintenance is better than BCG induction and maintenance. They say the benefit is statistically significant and clinically meaningful. We’ll have to see what they call clinically meaningful which is something sometimes not very objective and subjective depending on the reader.
BS: There have been a number of these trials combining immune checkpoint inhibitors with BCG and this is going to be the first one that will actually read out. So potentially the space of the BCG naïve setting is going to completely change and we’re going to be combining systemic therapies with local BCG therapy. So obviously in terms of cost that’s going to massively explode. But we will see.
AML: Yes, at the moment we are really waiting for new results. You might have seen the new release of the 2025 guidelines, actually in the NMIBC setting there is nothing really new this year regrading high risk BCG naïve or BCG refractory patients who move to it. This is because we are waiting for the results of all those trials and what you will find in the guidelines is mainly new stuff about de-escalation of treatment and active surveillance. So it’s interesting to see that on the one side there are some patients that we want to treat less, decrease the number of TURBTs, try to decrease the number of treatments, and on the other side we’re in a setting where we might be treating BCG naïve patients with both intravesical BCG plus immunotherapy. So treatments are shifting from one another and this is an interesting moment, I think.
FGR: What is important also to raise attention here is that we have the four pivotal trials with immune checkpoint inhibitors that still use BCG, either with induction or induction plus maintenance, which are the CREST which is going to read out soon, the POTOMAC, the ALBAN and the KEYNOTE-676. But we have two more trials, the SunRISe-3, which do not use BCG, just TAR-200 intravesically or combined with systemic cetrelimab, and the BRIDGE trial with gemcitabine/docetaxel. So we have two types of studies – those still using BCG and those who are skipping BCG and giving new alternatives.
GS: Let me also comment. I think it’s very interesting in the future to understand what will be the effectiveness of BCG as a treatment after failure of a population who initially skip the BCG into clinical trials. So we have no idea at all about how BCG will perform in this population of patients who initially fail, for instance, for intravesical drug release. We are making progress to delay the more we can the BCG refractory population.
FGR: Yes, my experience is a couple of patients who have failed these therapies with no BCG and they have recorded with a high-risk non-muscle invasive bladder cancer. I’ve used BCG for them of course and probably in the future if we get approvals with these new therapies we will have new definitions like X drug refractory patients or whatever.
BS: The next five years is going to be absolutely mind-blowing, isn’t it? Now let’s move on to BCG unresponsive disease. So you just mentioned that not much has changed in the guidelines, however we have got obviously a plethora of new clinical trials that are currently being conducted. What do you think, is radical cystectomy still a thing?
AML: That’s an interesting point. So the definition is a little bit complicated, you have the definition from the trials. Maybe we can remind what are the definitions to everyone who is listening because even myself I’m getting a little bit lost sometimes.
GS: I don’t want to be tedious with the definition but the point is that if you look at the guidelines we have patients who received BCG and recurred, the recurrence of disease, patients who were unable to receive BCG due to side effects, patients who are BCG refractory. So this population that is very heterogeneous is finally moved to a more practical definition in the clinical trials of BCG exposed. So all patients who received at least five out of six dose induction and two out of three at first maintenance are defined as BCG exposed. This is not meaning that patients should receive less BCG than initially planned. So we know from the EORTC trial patients should receive a complete dose, three years, full maintenance and this is more effective in the long run. But to define a patient who received enough BCG we are moving towards a more practical definition of five out of six plus two out of three.
BS: OK, very interesting.
AML: What is a little frustrating is that we’ve seen plenty of abstracts, even this year, about all the new treatments that are coming and we still have nothing in Europe. So in Europe we are in the setting where we are giving GemDoce or mitomycin or whatever. We’ve seen if you go to the abstract sessions in the congress for bladder cancer there are drugs that I even cannot pronounce the name because they are so complicated but that seem to be very effective – one of them has a response rate in the CIS population like 75% at 27 months of follow-up. So those are really interesting but I don’t know if and when we will get those drugs approved in Europe. So for now we are still in the situation, coming back to your question about cystectomy, where most of the BCG refractory patients if they don’t have the opportunity to enter a clinical trial are still going to go to radical cystectomy unfortunately.
BS: Thank you so much. Then the last point I wanted to ask about is of course about follow-up. So we know that bladder cancer is the most expensive type of cancer in terms of follow-up and treatment, has there been anything new at this congress that could potentially reduce the cost?
AML: Yes, that’s a really interesting point. We have been discussing this for hours in the guidelines meeting whether there are a bunch of multiplex urinary biomarker tests that are now on the market. Some of them have extremely good sensitivity and specificity, specifically for high-grade tumours. So those tests are not performing very well when you want to detect low-grade tumours but in the setting of high-grade they are performing very well. To date we didn’t have enough data to recommend the use of those tests so in the guidelines you now have a table that is listing the test for which there is the most evidence. But I was really interested to see that the [?? 18:29] trial that is investigating the use of expert bladder cancer as a follow-up tool in high-risk tumours showed that the rate of follow-up cystoscopy was halved in the population. So we went from more than 1,000 cystoscopies to a little bit more than 400 cystoscopies without any difference between the two groups of patients in the rate of progression and metastasis. So this is a randomised study, it’s a phase III, it’s just an abstract, we need to see the complete data and the publication, obviously, but I think some of those tests are getting really close to being used and are really, really interesting.
BS: Was this your highlight from this year’s congress?
AML: Yeah, I really liked that one. None of the patients want to get cystoscopies every three months, in the high-risk setting they have a lot of them. So if we can decrease that and really rely on a test, from a patient point of view this would be really good news.
BS: Félix, what was your highlight from this year?
FGR: Well, several very nice abstracts this year. In the first day in the congress, in the plenary, they presented two nice studies, especially the surgical outcomes after doing cetrelimab with or without TAR-200 in the SunRISe-4 trial. And this is the way to go in the neoadjuvant setting where all the previous trials have also reported, in fact you are the author of one of these papers, where you report that the surgical complications or mortality is not higher after these new therapies which is something relevant to know as well. Because if you are giving a therapy but it complicates your cystectomy and patients are doing poorer. So for me one of the big highlights, it was the plenary session, it was this abstract.
BS: Giuseppe?
GS: So the first point that we have more and more sessions on bladder sparing and this is an issue that, as urologists, we never wanted to really cover in the past. We are now facing the need for being involved in the bladder-sparing approach and, more interestingly, we have a lot of clinical trials in urothelial cancer. We are really now moving towards precision medicine that is a reality, for instance, for lung cancer, for breast cancer and I’m very happy we are facing the opportunity to be in the setting of precision medicine also for urothelial cancer.
BS: Sounds amazing. Well, thank you so much for discussing all of the abstracts with me and thank you so much for all of you listening to us and for ecancer for giving us a platform for this discussion.
