Clinical Insights: Evolving Landscape of Bladder Cancer After GU ASCO 2026

Hello everyone, I'm Rohit Gosei, a community medical oncologist. Alongside my brother, Rahul Gosei, another community medical oncologist, and we are the oncology brothers. Today, the topic at hand for clinical insights is "Evolving Landscape of Muscle and Basic Bladder Cancer and Non-Muscle and Basic Bladder Cancer." From Muscle and Basic Bladder Cancer, we already have FDA-approved option of gem, cysts, and with perioperative deval map. From this morning, what we saw was EV Pembro, presented by Dr. Matt Galski. For that, complex landscape will dive in. We have Dr. Chad Reichard from University of Indiana, Dr. Shilpa Gupta from Cleveland Clinic, Dr. Matt Galski from Mount Sinai, and Dr. Sia Danishman from USC. Welcome everyone. Thank you. Thank you, everyone, for joining us. Matt, can you get us started? Today, in Muscle and Basic Bladder Cancer, we have few options. Mpsis, Derva, Base of Niagara Child. We also have EV Pembro, Insus, Ineligible Disease, and now this morning, EV Pembro. What data do we have from these three studies? And are these three studies comparable? So three studies that you highlight, two of which are in a similar population. One is in a different population. So historically, as you know, patients you can't get cisplatin-based chemotherapy in the periodoperative setting, Sostectomy alone has been the standard treatment. And that's been the case over the past several decades while we've had an option for neolagement treatment for patients who can receive cisplatin-based chemotherapy. So the Kino 905 study filled that gap, showed that yes, periodoperative chemotherapy works in that population with EV Pembro. And it was a pretty striking result. I think one of the contributions of that study aside from just filling that knowledge gap is that if you were a doubter, that periodoperative systemic therapy works before, then I think that puts that to rest. The two studies that were somewhat similar are Kino B15 and Niagara. Those are both in patients who are eligible for cisplatin. And both had a similar comparator arm, gymsight, and being cisplatin followed by Sostectomy. There are differences though. There are some differences in the study design. There are some differences in the eligibility. There are some differences in the way that cisplatin could be admitted or administered on the control arm. And of course, because of those differences and different trials, we get into trouble when we do these cross trial comparisons. That said, both of them are positive studies. Both for the first time in 25 years, I have shown that you can advance, you can improve outcomes in patients with muscle and vasoblabor cancer beyond cisplatin-based knee lage, when chemotherapy followed by Sostectomy alone. The data from Kino B15 shows that the primary endpoint of event-free survival was met with the hazard ratio of 0.53. And overall, survival benefit with the hazard ratio of 0.65. And a path CR rate of 55.8%, which is really among the highest that we've seen. >> Yes. Well, thanks so much for that background, Matt. Shilpa, with that background in mind, I'll ask you an easy question. This is for cis-illigable, cis-dectomy-illigable patient population. We know both of these combinations work. That is, the Agri-Trial-Gempsis with Peri-OptoVal-Mab and EVPembro. Tomorrow in your practice, are you going to pick amongst the two options available, keeping that patient in front of you in mind? >> I think, like Matt, I'll find the big thing now is that cisplatin eligibility is a mood point. And I think EVPembro is the regiment for everybody. We don't really have to think about cisplatin eligibility anymore. And I think it's unprecedented that CR rates, 58% no matter what regiment we've used before we've never seen that before. And without doing cross-trial comparison, but doing some of that comparison, I think this data cannot be picked. So I will be offering EVPembro for MIBC patients. >> Right, with all this, one has to keep side effects and efficacy in mind. We know that both of these combinations are efficacious. But with regards to the side effect profile, could you comment a bit on the side effect profile and some clinical pros around these combinations? >> Yeah, so, you know, Gemsis is what we've been using for decades. We're very familiar in the community or in academic settings. And Gemsis, their value map, did not have any additional toxicities that we were worried about. And I said, I think, you know, we'll see more data that comes out of the B15, but the key message is only 51% patients complete in the periooperative regiment. So that is a high, you know, 50% did not. So we need to understand what was the reason a good chunk of patients did not complete the new adjuvant treatment or discontinued it. And I think Matt, I asked you this question today that, what they able to resume in the adjuvant setting, you don't know that. And they able to undergo cystectomy without complications. We don't know that. And I think 28% patients could not complete the adjuvant portion. So I think this all points to the fact. And we've seen that in EV3 or 2 that despite those reductions and those discontinuations, patients receive benefits. So it almost sounds like patients may not need so many treatment cycles or duration. And we just have to figure out. And it does seem, you know, over 70% patients did have those toxicities and gymses is a regiment which every oncologist is aware of. EVPembro is one regiment for one disease. And I think it'll be very important for the community docs to understand the nuances and on the toxicity management. They're very unique, very different and cannot be preventive. They just have to be managed and be coactive. No, can I just piggyback on where you're leaving? EVPembro as if now is only in bladder cancer. Gem, sis, immunotherapy, their valumab, we've used this now in upper GI malignancy on using this in lung cancer. So out in community, there's that comfort and it's important for us to appreciate the side effects of inford to map. Rash, it's not mild. You have to be very careful with that. Neuroopathy, hyperglycemia. So we have to get comfortable around these side effects. And Rahul, I just say that even physicians that certainly be are comfortable with chemotherapy, but also staff knows how to manage some of these side effects. So that will require some education there. And then when we're talking about these systemic treatments and new adjuvant, periop settings, the idea is it's helping with that local control, but also helping with the micro mats. But with all this, if this is a surgical candidate, our goal is to get our patients to radical cystectomy safely. So let's get our urology colleagues on board here. So, what are you making out of the available two options? I would love to hear two things. One, and both these options are the surgical outcomes comparable to when you're sitting in that tumor board. Do you have a preference based on the data we're seeing or the comfort around the chemotherapy from surgical perspective? Yeah, great questions. And I think the conversation is still developing. This is brand new information. And obviously we anticipated this having seen it in the cis-ineligable populations. So we've been using it. EV Pembrane is this ineligible where we didn't have anything. We were going straight to cystectomy. So certainly, it's a conversation. Your points about the side effects are very well taken. I mean, these are patients we see post-estectomy. They're already having complications. Now they have the lingering sort of neuropathy from maybe that can be pretty significant. This is very different than neuropathy that we see with this pattern. It can actually be long lasting. So some things to keep in mind. Of course, so the real question is, does it affect your surgery just based on the complication data that Matt, you presented? It doesn't seem to me that it's affecting the complications of surgery. They're so high anyway. It is right that we're used to these high numbers. So I don't think whether you use EV Pembro or Gemsys Durbra that it affects the quality of the surgery. What I am seeing, especially in the past, where patients have locally advanced disease, are getting EV Pembro from my colleagues. I'm hearing, you know, it was a really difficult surgery and everything was fibrosis. I'm like, well, the reason it was fibrosis is because they have such a very good response. Absolutely. And of course, we see this in testis cancer and some anoma treated with BEP. We get this tremendous response and hence a tremendous desmoplastic reaction. So I don't think it's regimen related. I think it's response related. And so I have the feeling that immunotherapy in and of itself does not alter surgical plans, nor does it alter your perioperative outcomes. Well, thanks for highlighting that, Sia. And what you're alluding to and what Roblstar was also a multidisciplinary approach where that partnership, but we medical anthologist and urologist is going to be the key. Chad, with your regards who's out in community from urology standpoint, how does that partnership currently look like when you're tying in that urology colleagues as well as medical oncology on that table? Yeah, I think it's very important to have a close working relationship and communication and open lines. We know that timing of surgery matters. And just as we've heard with the data, patients not completing all of the prescribed treatment, there's variability that's introduced into the system. So understanding where the patient is in their journey in order to pick up and potentially take them to surgery earlier, if they're struggling with the new adjuvant portion of treatment, not losing them when they're complete and intervening in the appropriate time window. I think our very important considerations, and it takes a team to make sure that happens nursing navigators are very important to keeping these patients following along their treatment path. Yeah, so multi-dekeeping side effects in mind and then chat you touch the on the team. It's not just us as physicians, your nurses, we touched on this as well, educating everyone who's involved is going to be the key here. Matt, coming back to you, you've been closely involved in almost all of these studies. Looking at the data for EVPembro, where is GEMS as Derva going to fit into your treatment landscape? What about that cis-borderline patient? So, cis-bletten borderline patient probably is less of an issue, given that we have the Q905 data, but I think there's still a lot of uncertainty about what to do in patients with your ethereal cancer with variant histologies. It seems like on the one hand, we focus on bladder cancer. It seems like maybe this is a sort of topic, but in reality, it's probably just under-recognized, and it's fairly common when you start to look for variant histologies. Because we're basically, we have two sets of drugs with these regimens, cytotoxytherapy, anemia and chaplain blockade, or ADC and anemia and chaplain blockade. If you bet wrong with one of those drugs, then you could get into some trouble in terms of optimizing responses. So, giving an ADC that targets necked into a patient with a tumor that has zero necked in expressions, probably not the right thing to do. We have data at the gene expression level and at the protein level in some small series from different institutions looking across variant histologies, which there are many with some showing necked in expression, but some showing very little. And we don't quite understand how to treat those patients yet in which regimen they should receive. May I add something? So, you know, for the patient with borderline cis-platant, one of highlighted in the Niagara trial, it was a forward-looking trial, they didn't use those. And Gasky criteria for creatinine care. So, they were a good chunk of patients who were actually cis-platant in eligible because the creatinine care was born and you can easily and safely get split dose. And I agree with Matt's point about variant that also included that and note positive tissues. Yeah, I want to reiterate that. In Niagara trial, we had a good portion of our patients that got that split dosing. So, keeping that in mind, Matt, I want to come back, you brought up ADC. There's buzz around that. EVP is chemo-free regimen. I just want to reiterate that this is an antibody drug conjugate saying it's a better delivery mechanism for chemotherapy, but this is still clearer chemotherapy. I've touched on some side effects. Can you expand on what common side effects we saw in these two trials with EVPenbro? So, I completely agree with you first of all. And when I talked to patients about this, I told them it's chemotherapy because it's chemotherapy. And in these studies, the, you know, gymsis performed as you might expect from a side effects profile standpoint, we're all familiar with that. EVPenbro, paritis, diarrhea, jalopecia, rash. Those are sort of differentiators with that regimen versus gymsis, which is more hematox, anosia, et cetera. And Matt, just diving into this further, we've talked about briefly that some patients were not even able to complete the knee-adjuvant part of the treatment. Any role in your clinical setting starting tomorrow where you start with EVPenbro, if they can't get that, would you switch to gymsis, Darva, in that setting at all? It's a great question because we have single arm studies with both of the components of EVPenbro in the knee-adjuvant setting independently. And we know that each of those drugs independently has a not insignificant path CRA. So whether or not you drop one drug and continue versus switch, I think is a great question, depends a little bit on the toxicity. And it depends a little bit on the timing too, right? If it's after three cycles and you're planning to give four, then maybe just give one cycle drop in one of the drugs. Yep. And Shilpa, we've talked a bit about the path CRA. That's how we started with the data that we have at hand, whether that's with Niagara or what we are seeing with keynote B15. Any role of dropping that adjuvant post off IO if we do achieve Patsy R. I think that's a really good question. And the problem with all these perioperative trials is that the new adjuvant and adjuvant portion is not separated, like me doing in melanoma and now starting to do in lung. And that's why we left with this, we're going to be left with this majority of patients who may not need adjuvant because if you were to look at checkmate 274, or any of these adjuvant IO studies, you had to have residual disease, key to our higher. And now we're talking about treating patients who are PT-0 with months and months of EV and PEMERAL based on the trial data, when only 50% of patients may be able to get to. So I think those are the questions we need to really tailor treatment based on the patient. In front of us, maybe use tools like CTDNA. Obviously, we can't do a new CTDNA, a prospective trial with every regimen. So we just have to brainstorm on what is the adequate number of cycles. And once we have more information from the paper, we probably know better. You know, I want to expand on that because again, we're all looking forward to this radical systemic to me free error because your response rate is so good. But this is not ready for prime time. Today we had data from Niagara trial that even if the CTDNA was negative, I believe it was Joshua makes who presented that that there was value of continuing that post-op to value map. So I think that this is where we're headed. But today, I don't believe it's ready for prime time. All right, CTDNA is certainly a hot topic and these are just exciting times. What we're going to be seeing in future also is the wall gut trial, which is Derva-Lumab from Elimimab with EV versus Derva-Lumab plus EV, Matt. Before we move on to non-muscle invasive butter cancer, where we're going to give the stage to the urologists. But since we have these two combinations now, that is Jemcis, Periab, Derva, or EV, Pembro. How is the sequencing going to look like in the recurrent disease? So it's going to depend a little bit on timing, I think. And of course, I don't have data to back that up, but just based on oncologic principles. And I think coming back to CTDNA, that's where CTDNA could potentially be helpful, and I'll explain. But I think it's going to depend on timing. Someone who progresses while on one of these regimens, of course, it's not the right thing to do to give it to them again. Someone who progresses off of treatment, it might make sense to do it again. And I think, at least for me, historically, I've thought about periodoperative systemic therapy as curative or not. But I think there's, it's actually, it's a little bit less clear cut than that. Just like in the metastatic setting, there are probably patients who respond to treatment, but don't have disease completely eliminated in off treatment, develop progression, and might respond to the same regimen again. You know, these are exciting times. Now, let's dial the clock back to non-muscle invasive disease, Rohe het. You brought up our urology colleagues here as well, because you tend to take the lead here in that non-muscle invasive disease. We've started to see medical oncologists come play a role with Pembro and selective patients here at GU Asco, RECING Data Run Potomac and Crest. So you're starting with you. What are relearning from these two studies? I/O/BCG combination is going to likely play a role. And medical oncologists will start to get involved, even in non-muscle invasive bladder cancer. Yes, certainly. The lines are blurring in a good way. I see it as a spectrum of disease, and there's closer communication, I think, between us here, urologic oncologists and the medical oncologists. So I like that, because again, to me, it's not a clear cut, you know, non-muscle invasive, muscle invasive, but it's continuing. But yeah, we're certainly seeing systemic therapies being used for non-muscle invasive bladder cancer with three trials. Albans was negative, but we had two positive trials. The Crest and Potomac, with the use of either the Dervolamab or Cessanlamab, which is a subcutaneous injection, I/O, to augment the effects of BCG. So for years, no one wanted to go head to head with BCG or make it better. It's already so great, and it is great. It is still a very, very. Absolutely. Therapy for an arm muscle visit. Can we make it better? Of course. And so that was the point of these trials. Now, two positive trials, they met their primary endpoint, and so for all intents and purposes, it is a successful trial. But then you come to the practical portion of it. You know, these patients coming to our office with non-muscle invasive bladder cancer to the community, and now you're saying, "Oh, there's a trial that showed improvement. Okay, what is that improvement, and what are this side of profile?" You know, we've already touched on side of that profile of the various drugs, absolutely. And so we are now well aware of all the potential side effects of checkpoints, and in 15% of patients, you have some significant side effects that could be long lasting. So we have to have those conversations with the patient that, you know, these could be lasting side effects. This is not a rash that will go away. Maybe on our replacement, now there are people the rest of you live. So the question is, you know, when do we use it, and how do we use it? There are subset of evaluation of patients. I think it was brought up today in the discussion to patients with the highest risk for not just recurrence, but progression are high grade T1 with it without CIS. And I think when you look at that portion of patients who may be heart-wiring some systemic disease on top of your nonmuscle invasive, of course, it's nonmuscle invasive, but it isn't basic, right? So perhaps in those patients, super high risk, multifocal, we already have some clinical features. We use some variant histology, lymphrovascoinvasion. Yeah, it might make sense to do BCG+ checkpoint inhibitor. So that's how I'm thinking about it, but a patient who has a high-grade TAL that we resected we're really using BCG. in the Antiband setting. We're not worried about systemic disease. I think BCG does just fine. All right. Absolutely. Well, thanks very much for summarizing that. So yeah, with regards to the data, we have a hand with BCG+ Dervaulamab. It has a ratio of 0.68, but here Dervaulamab is for one year with BCG+ and Cervaulamab. The hazard ratio again was for 0.68, but again, this is for two years. Chad, would you go to if this was to get approved with BCG+IO, who's going to take that lead role in prescribing the immunotherapy and managing side effects? You, as urologist, out in community versus medical oncologist. Yeah. So we do use immunotherapy in our practice, you know, certainly in the adjuvant, renal cell space. And so we have familiarity with it, managing the side effect profiles and so forth. And so with the monotherapy, immunotherapy, of course, in addition to the BCG and we would do that. And I think that's where the discussion comes in with the patient, and able to manage them and explain to them as, see, it was talking about, you know, the risk-benefit profile. And yeah, I think really honing in on those patients that have multifocal T1 papillary disease with the RwthCIS. So those patients that you're worried about a higher risk of progression may be much more likely to benefit from a treatment that has a higher side effect profile. So of course, you know, we think that, you know, managing these side effects is doable in the community setting. And so, you know, it's good to have options for our patients. You know, if I was to put my money on it, I think it'll look a little different in community settings where I do think that urologists likely will take a little more lead on prescribing immunotherapy exactly to what you've shared with your experience. And I think it might look a little different in academia. So let's ask Matt, Matt first, your impression as a medical oncologist on these two studies, keeping that has a ratio in mind, keeping that treatment duration with the atomic we're talking about one year of the ValuMand versus two years. What are your thoughts and who do you think is going to take the lead in your practice? So I completely agree with Cia in terms of trying to identify patients at the highest risk. There are patients who we just worry about who come to us with non-muscle-based and disease. They're usually the patients who end up saying me as well because they're worried also so they want to see a medical oncologist also. So yeah, I think who those patients are, they self-select a little bit. In terms of administering treatment, you know, one comment that I've heard sometimes is that, well, it's just the subspecialists who end up managing the side effects of a MiNCHEP point blockade anyway, your gastroenterologist or endocrinologist. I have to say in an academic center that's still not really my experience unless it's, unless it's a subspecialist who has an academic interest in managing these side effects and oftentimes were looked at for guidance in terms of what to do. Can't tell you how many times I see a note it's deferred to the medical oncologist for steroid recommendations. So I don't think it's very poor. I think a medical oncologist in the loop, like you want to human in the loop with AI, right? I think you want a medical oncologist in the loop with MiNCHEP one blockade. We always watch in the loop. It's true though, at least in my practice, I am leaning into a GI or that cardiologist for that refractory side effect that I'm not able to manage and leaning into them is important. Shopa, from your perspective, these two positive trials. Can you comment a little more? And if the I/OBCG was to become available for that patient who was part of the inclusion criteria, high risk, non-muscle invasive bladder cancer, is this combination going to be a preferred option? Yeah, I would echo what Sia said. The long-term lingering toxicities are not minimal for this patient population who have non-muscle invasive disease. For medesthetic disease patients, they expect to deal with those. And I think the big difference between Christ and Potomac from my point of view is that two years versus one year, we've never seen a saturday day dining wear else. And I don't know if it's just a more toxic I/O to begin with, then two years. I mean, I think 45% patients had serious adverse events, which is not minimal in this setting. So I think that's a big trade-off for a regimen where we don't have overall survival benefit and what are we gaining out of it. And as far as if this were to become the standard, I think we still rely on our urologists. If they think somebody needs it, you know, if they are very sure the patient with benefit, they'll be referred to as and and I hope they are referred to us because you know it's not about administering a subcutaneous drug and saying goodbye to the patient. It's about taking those calls in the middle of the night and I'm sure a urologist resident or fellow taking calls for stones and hematuria and then myocarditis or you know these can be fatal side effects. So I hope that we will really keep the medical oncologist in the loop because it's about the management and not the drug administration per se. But yeah, if I say urologists want someone to get it, we you're not going to say no to that patient, but it's someone where to come independently like a lot of these patients want a medical oncologist opinion, you know, then we are going to discuss the data and discuss the side effects at Great Lent. And again, coming back to what we were talking about earlier as well, there's that comfort in medical oncology that we've used immunotherapy across the board, not used the crest regimen, but for dervallimab, I've used this, pemoralism, I've been using this. So there's that comfort in managing those side effects. But coming back to Crescent Potelmic, not only two years and one year, the efficacy data looks very similar as well. So I think that's important to reiterate that. I'm not compromising any efficacy here by not giving that extended duration of immunotherapy. Well, thank you all. We've covered quite a bit. That was a complex landscape, but thank you so much for walking us through that. But before we close, key takeaways from the conversations that multidisciplinary approach is rather the key for muscle invasive bladder cancer for cystectomy eligible, cystilligenable population. We have two combination. Gem, cysts with periob dervallimab, and also evy pemoral while we are waiting on FDA approval for non-muscle invasive bladder cancer. We are seeing data on BCG plus IO combination. We'll see how regulatory approval plays out. Thank you so much for all tuning in. We are the oncology brothers. [Music]