How to Treat Bladder Cancer – Drs. Stephanie Berg (Medical Oncologist) & Joshua Meeks (Urologist)

Hello and welcome back to the oncology brothers podcast. I'm Rahul Gossane here as always with Rohit Gossane and we're two practicing community medical oncologists. Our hope with this platform is to keep you our fellow oncologist up to date and all that is happening in the world of cancer. Today we're focusing on the treatment algorithm of bladder cancer. This is already starting to look different post-GU ASCO 2026 as we're seeing some new data in non-muscle invasive and muscle invasive bladder cancer. To help us go through the data in hand, we're excited to have both our panelists at the same room Dr. Stephanie Berg, a GU medical oncologist from Dana Farber and Dr. Joshua Meeks, a urologist from Northwestern Medical Group. Josh and Stephanie, thanks for joining us. Josh and Stephanie, welcome. I know Stephanie, you're welcoming Josh here at Dana Farber. Well, thanks so much for taking the time to do this. Starting out with non-muscle invasive bladder cancer space, where medical oncology has had very little role to play here, even though majority of bladder cancer patients who are diagnosed are indeed non-muscle invasive bladder cancer. Historically, BCG is what we have relied on. And more recently, we have seen few advances in this field where BCG is being combined with I/O for that high-risk non-muscle invasive bladder cancer space. We have two positive studies that we have seen in the space. That is one crest with Susannah Mab and Potomac with developmental map. Josh, given urology does take a lead here, can you touch on current standard of care and what are we learning from these two positive trials here? I think what we really learned from these trials that were huge endeavors, right? 1,000 patient trials, really, trying to be BCG is a standard. And I would say that's the biggest take. If you give BCG, if you give maintenance therapy for a minimum of a year, longer if you have access to BCG, it does really, really well, right? You can cure almost 75% of patients. So then the question is, if you look at the data, there's a benefit to giving I/O in patients. And that benefit really comes to events. I think that is the key point. And that's been the challenge from regulatory perspective, because multiple of these trials have hit their endpoint from an event point, but they really haven't hit it from the progression point. So when you're having that discussion with the patient, and again, they're not FDA-approved as of today, the real question is, will there be a role in who you give those to? Because you're not saving lives. Like if you could say that you're improving survival, then there's patients clearly with higher risk cancer that you're going to hell, but for now, you're decreasing events. So I think as we look at survival as a long-term employment, we don't have data on yet. The main challenge with this disease space is there's a lot of deaths that just happen to our patients. A patient with bladder cancer has a risk of death overall that's not necessarily related to their cancer. So are we going to meet that endpoint? And I don't know for there yet. I think in the ideal world, these drugs are available because there are patients that are not the same, that are higher risk. I think your best chance for curious early on getting the best therapy. I mean, how do you think about patients when they're going to come in and ask for it? I can say that I don't get a lot of tutorials from our world. It's just from, you know, like Mark and Matt and Adam and everybody, but it is something that as the medical person who gives the immunofarabies, I mean, it is a really solid conversation because these are light-voltering things that can happen from immune and related at our spines. But it is a really heavy conversation because I completely grew me without that actual, as Matt or like survival, are you, you know, what are we, are we causing more harm? Because yeah, BCG works really well. I think it's a great point. So there's patients that are higher risk that we see that. And you probably think about suspecting me as like, that's our nuclear option. And then we have ECG. And so there's nothing in the middle, right? So if you have like prosthetic urethral malpents, if you have an LVI, if you're variant histology, our guidelines say suspecting me for those patients. But as we're going to talk about suspecting me for muscle and basic disease, maybe involved less. So to now talk about that, in early suspecting me, he risked there was something in the middle that could give a little more activity and bring those people back. So I think that's really where the space needs to develop is people that are super high risk that you'd love to give more to. But a suspect me like again, whether you cure them or they have no disease, their complication risk is there, right? Then risk of death from surgery, life changing complications is there, no matter what the oncologic outcome is. So you love for something in the middle to be there as an option for these patients. You know, the question is do you go a little stronger or really, but now that you have like five drugs or FDA approved after BCG. So having a good secondary net, is that, is that, where does that come in? I don't know. I mean, I think the challenge for many of these is those, all of those drugs while available are not the easiest to give. There's a lot of rabies for issues with giving those drugs in the office. And while effective are extremely expensive. And so, but we're really starting with that from, I mean, we're having to deal with all this preauthorizations that don't we throw our fusion centers? Yeah. Give me them, especially like, your allergies don't do that. I mean, BCG is very affordable, very musical. All of those drugs to give them, to coordinate them. I've never worked so much with our pharmacists and fusion centers. That's something that we now have to do that you guys have done for a long time. But for example, like in Lexo, is that FDA approved? That involves a scope pulling the device out, putting the new device in. For me, that is really the next surgery, some things that we have to deal with. So just if we thanks to reiterate, Stephanie, you brought up that you've not seen many of these patients because historically, Medicron colleges were not playing a big role. And coordination is going to be a big or a deal here. Roat, as you pointed out, majority of the bladder cancer is indeed non-muscle invasive disease. So we'll be seeing a lot of these patients again in our clinic if I/O/BCG becomes a reality. So when we're talking about data in hand, two studies, Crest, Sensil and L'Mab, is for two years, Potomac, Dervalumab is for one year, with almost identical disease-free survival benefit. Josh, coming back to you, in terms of coordination, if this becomes a reality, I/O/BCG is available for that high-risk non-muscle invasive bladder cancer. Who's going to take the lead in prescribing that immunotherapy? Are you going to lean into your Medicron College colleagues or do you feel comfortable as a urologist moving forward with us? Well, I would say in 2026, we don't feel comfortable. It's not been our role. But I do think that it depends which, if either the drugs get approved. So if it's Dervalumab, obviously that's an infusion that's going to begin with Medicron College, but will urology have to learn? Because there's just too many patients for uphotopic getting patients in that have life-threatening muscle invasive anesthetic cancer. But that's got to be the priority. So when we take some of that, I think we'll need some education, right? It's a big tent, right? It's managing the AEs, it's managing side-like us and our ABVs. Don't do that now. So there's a lot of education that will have to span that gap. I worry it's absolutely on the other side of it. If it's the sample amount, if it's an injection, that's a lot like that vehicle be much quicker to us, but the educational gap is still there. So I think there's opportunities to learn. And again, one of the things about urologic urologists that take care of these patients is that they like to learn this stuff. So I think there will be those interests in doing it otherwise you just need a partner. Yeah, absolutely. I completely agree. I think, you know, it is something where in Medon, we've been dealing with IO treatments for more than a decade. So I think it's more just finding the patients we know are appropriate to receive these because that's a lot of treatment. It's a lot of distance. It's a lot of things that can happen. Like you said, we're not really a life threatening disease, but it's still disease, but right, it's a lot for each to go through. But again, I roll, I feel like this is going to look different in different settings as well. I know urologists would prefer being in surgical room while medical oncologist in infusion room. But at the end of the day, community urologists are administering pembrolism at. Absolutely. No, I think they will look different in community versus academia. All right, now on to muscle invasive bladder cancer. Here historically, we had gymsis in neoageven settings or radical cystectomy if patient was cis and eligible. Then we saw approval of gymsis to valumat based off Niagara trial that resulted in an improved PCR and overall survival with the sandwich approach. This quickly became the new standard of care, but now with the data of EV Pembro from two studies, EV 303 and EV 304 were in Fortamabvedotin and Pembro are given in periopsettings. We're seeing a significant improvement in PCR. Stephanie thoughts on our available options in muscle invasive bladder cancer, recent data that we just saw at GUSCO 2026. And importantly, with all this, where is Niagara regimen going to sit in your treatment algorithm? We think that we all anticipated when we were at GUSCO coming off with 303 and 304 that this was going to be the new standard of care. We're just waiting for regulatory approval. This is eligible setting, but with high-paciarates over 50% toxicities that I would hope most medical oncologists have been dealing with since the last few years. I participated in the for each one of three trial and when I was in Chicago. And it's It's just something now what kind of needs to. So I don't know where the Niagara Regimen really has to roll right now. I think Latin Quimau is extremely important and we'll talk about subsequent therapies, but I think with when you're going in, and again, a little bit different with the three cycles, of course, the four cycles in a period of setting, originally we always were doing three, and then now they're like, oh, baby, you need to do four with side effects. I think as long as the surgical outcomes and people are getting cystectomy and it doesn't have really made any difference in how you do the surgery. - I only think about is, right now, we're looking at PCR, and if you look at the new adjuvant portion, you're getting basically the same length of time, probably better PCR, you can compare, but in general, the PCR has seemed better, right? From three to three, three to four times. But the tail of that curve is the adjuvant part. So I think my sense in the US, I mean, as the urologist here, people are still trying to pair with you with the adjuvant setting. - Yes. - Which, if you check point, you're in the PEPRO, the trials give a lot of therapy efforts. Now, if the angra rolled into dervaluedin, which is a much more tolerable. - Very tolerable, yes. - Monthly treatment, yes. - So if you look at the whole thing, there may be some patients where up front, you give that, and then someone they think of, right? It's like, you're less kebob overall, 'cause you're just giving the new adjuvant, you're not having the adjuvant, chemo words. But my sense is I don't know how often you're gonna be giving the adjuvant, maybe. - I think it's, I think vulga, I don't know what vulga is gonna read out, maybe an Esmo, and because that does not have that adjuvant, it just has the new adjuvant in part. I think there's, you guys have seen this too, from a lot of UV is quite toxic. So after you have a major surgery, like a radical septumine, which has complication rates, putting a person on the same regimen and say, you have to do five more cycles of this strut that's a hard conversation. So vulga is a study that's also looking in the same space, and it's really the bigger question of the perioperative setting is, I believe there is a C-T-L-A, there's a C-T-R-E, right? I think that is correct. - Yes, that is correct. - But the answer is what we're really all interested in is because they decided to not proceed with an adjuvant portion of the ADC, and that is really the big question, 'cause I think a lot of us have a, you know, our results is like to not continue EV, but if you wanna be that pure tri-list person, you're like, well, I should continue it, but if they haven't passed the offer, our adjuvant data from, you know, Checkmate 274 from our Alliance ambassador study is, they all had disease, right? They had pyrosidine. These patients are going into adjuvant therapy, but no disease. So that is, that's been a test grant, sure. But I agree, like, I was sure fine, we can do it for a little bit, but you're pulling that therapy off really early if they're applying any trouble, which most do. It's not easy. - Again, I feel like with any of these studies, what we're trying to do is, can we do better from each of these studies with WOLGA, what we are trying to see is that immunotherapy here, dual checkpoint inhibitor, which is Dervalemab, Tramilomemab, and now tying that EV arm along with that. We'll see how that plays out, but again, no one can deny some robust results from what we saw with EV304. It is again, practice changing. With regards to urology standpoint, Josh, the goal is cystectomy, which is radical cystectomy part of any of these trials. However, any way we can avoid that, because again, at the end of the day, it does come in sweat fair share of side effects, especially for that PATH-CR, or rather complete response from imaging standpoint population. - Yes, I would say that this has now become the easy button for urologists, that's really the discussion with they meet with us, 'cause somehow they usually come to us first, 'cause we're doing the TURBTs, is listen, you have this cancer, this is your neck stop. - Yes. (laughs) - Right, like with your in-1, metastatic pulmonary nodules, or just muscle invasive, doesn't matter anymore, what you wanna do with your bladder, doesn't matter anymore. You just need to go get this therapy. - Yes. - Because that's what saved me lots, right? cystectomy's been around forever. - It will be around. - Well, we've not cured people with it, right? And so that fixes that problem. - It does. - Now, what I tell them is go get that, and then let's come back and talk. And so people who's glad, I think they want to cystectomy, we can do that. I actually, I talk to people, they want tremolable. Let's go take a look at your bladder and see how it looks. And we don't want to much about those non-responders. You got EVPenbro, and you didn't respond. If you have muscle invasive disease afterwards, even though some data from retained suggests cystectomy doesn't do well in that population, I don't think they're gonna do well. - In general. - So for them, I'm telling them, I think cystectomy's their best option right now, right? 'Cause we don't have a second line set up. But if people want to preserve their bladder and they're at T1 or last, I think at a bright trial or tremol, it is the bed, it was a very reasonable option for them. - I completely agree. I think it's a good conversation to have to not automatically go to a septumine, because I think a lot of indications are asking that too. They're like, well, if I have no evidence, I'll have to buy cancer. And we have really great MRIs now with our cystoscopy. And we're gonna obviously talk about can I have a bladder discussion without CTDNA? You wanna try to preserve that organ as much as you can. And it is really that discussion with, to do that because it is something that, if you're, what disease you're actually treating, what's left over because yes, cystectomy is, but it's still important though to have it around, and see what we do. But I agree, you're a refractor to EV Pembro, that is, you need a large, you need a clinical trial, or something like that. - And again, whenever we are talking about these conversations, whether it can be avoid cystectomy, or can be avoid post op adjuvant treatment, this is again, we are trying to battle here is the overtreatment issue, whether that's from urology standpoint or medical oncology standpoint. And again, Stephanie, you said, bladder cancer conversation cannot be complete without CTDNA. Now, any role of CTDNA, especially in PADCR cases, can we avoid adjuvant treatment here? - I think with 11 in a bigger, I think there is an emerging role, and it's coming in where it's really, usually specifically the niteris passe, which is tumor informed, is really a conversation that a lot of us and solid tumors are really having, and it's not a perfect test, but it is something that can really be really, patients feel really happy that it's negative, but then bring them extreme anxiety when it's positive, and yet you don't, and you have a clinical complete response. So it's emerging, and I know there's gonna be some FDA regulation about this device that's coming through, and we're using it in large clinical trials through the quadrature groups and through the company itself to kind of gauge like what is measurable residual disease? What does this actually need for your patient versus some of its competitors, they're doing these crazy, whole genome assays that are tumor agnostic. How can we make sure that we're keeping the people that don't need treatment off, and then treating the people that maybe need it sooner, getting them on it? So it's really exciting and get my stochematology before. So when we did MRD in leukemia, that was like, they're like, "Plan out, "we'd all these really cool drugs, "and then now it's coming with us, "and maybe we can use IO or EV to clear it." We know it looks good, but it's not, it's not time-time yet, but it's really, I mean, every conference, they're just something coming up and you're like, "What are we doing with this?" - Again, this is across all disease sites. You touched on hematologic malignant disease. We're seeing this, of course, in colon cancer, this comes up in breast cancer as well. And data that you presented in the past, Josh, that even with Niagara trial, when we saw CTD and a clearance, there was benefit of ongoing devaluemab. So again, is this ready for prime time, perhaps not, but something that we're all eagerly looking forward to? Okay, so far, what we've talked about is when radicals of stochomy is the goal. But what if surgery is not an option due to patient being frail or personal choice? Stephanie and those settings, we're often relying on concurrent chemo radiation. In those settings, what's your chemo partner? - Get pretty, I mean, I'm a big, still believer platinum is king of the setting. If you can get platinum, it is the best one. So I just do weekly says platinum, but I know there is, we have a, you know, right at the right time. And I think it's been more like Josh was mentioning where we're even doing parry operatives. So meaning doing like a neododudent EV pembro and then doing even consolidation. But it really does depend on the patient's frailty because if you're giving twice weekly gem for an older, you know, man, it is mid-80s, I probably won't want to get them so much EV pembro at the beginning, maybe just do something with radiation, which is, you know, pretty good. So I know what you think. - Yeah, I mean, I think that, again, we're trying to over observation fits in there. I'm not totally certain. I think that needs to be studied right. And like a randomized trial of people who essentially are succinct and refusing everyone to keep their bladder and see what's the best in toxicity. It's hard to know, but I would say that those people should be needed to handle. - Yeah. - Like if you're keeping your bladder. - It stays at night. - Those are the people who at a minimum should be following the protocols, which is what they can tell them. - Right. Which is usually again, if we do like this parry operative, some I/O where I've used the NIEG or regimen for some trained models, you just kind of continue to derb at me. And I/O with radiation is okay. I mean, it's, it can be since testing. So. - Absolutely. And we have strong data there. All right, now on to metastatic disease for the last few minutes. either after treatments, upfront for that muscle invasive or denovometastatic disease. Big question here is what next after reduced EV Pembro? In metastatic settings, EV Pembro was approved based off EV-302, which resulted in that overall survival doubling. From 16.1 months to 31.5 months. And that has a ratio of 0.47. So we're using EV Pembro upfront in metastatic sightings as well. Stephanie, your thoughts here for that recurrent disease after EV Pembro in muscle invasive bladder cancer? Or if the disease was to progress on EV Pembro in frontline metastatic sightings? Yeah, it's that curve that we always think about from the new English journal paper by Tom, where the curve is good, but there's a gap where it goes down. And it's like that first gap of all those patients that progress that hell is the balance like, I don't really do better for them. And I think most work are going to reach for your platinum because, sure, why not? You likely won't re-challenge it with immunotherapy, but I think don't have any biomarker-directed treatment option like FG-3 or even now, or 2, 3 plus, which is for TXT. It really is a, that's a really tough population. That is something where I think in the community, thankfully, these are all genomically driven and they're all available on the market and try to get your patient into a clinical trial if they're fit. One thing I can say about your field cancer is that a lot of our trials are expanding their form and status up to a two. So it's like, they're really trying to make sure that these patients can be a little bit sicker and then see all these therapies. But I don't think we have a right answer right now. We're at the Mcregor's trial where we're actually doing a triplant. It's a Sassy EV and Pembro's we call it "Daddy O" and so it's a dual antibody drop time to get and we're seeing really good responses but it's a little toxic. So you have to be really fit to get that regimen but it is a really important area of need and even with like the descent of the dote and coming in with the HER2, there's a lot going on but these trials are tough. Before we close, Stephanie, one last question is if the disease was to progress and we have to do biomarker testing that as FGFR alteration or even HER2 positive because we have targeted therapies available. Do you tend to utilize on disease progression in second line or do you keep them for third line and rather keep platinum for second line? So this rare to have an FGFR3 and HER2 at the same time, I think the one thing that's easy about HER2 is that it's an IHC. It's really easy to get. So if you're standing there, I don't think we know the order better. I think the the four trials from ERDA have larger phase three studies with their their survival. Her number is like this really small study that was kind of this pan tumour study and so they kind of just like put platinum in there. And you actually stated from GUSCO, the biomarker's not perfect. It's not perfect. The right responses were good but low and high, even a low there may be some activity. And it's a really well tolerated drug. So I think compared to what we know about these AFGFR3 inhibitors with some of the pretty severe toxicity and there's new ones coming out that quite at the market, I think there's no wrong answer. I think maybe the HER2 is a little bit nicer story and a little bit more tolerable than the AFGFR3, but now it has OS. So you should always look, but the co-localization is pretty infrequent, but it can't. Stephanie, thank you so much for touching on that. We're eagerly waiting to learn a little more on how to sequencer available options, particularly in this refractory settings. We've covered a lot here in a very short time. Stephanie and Josh, thank you so much for walking us through your treatment algorithm for bladder cancer. For those tuning in, let's do a quick recap. In today's discussion for treatment algorithm in bladder cancer space, we started off with non-muscle invasive bladder cancer, where we touched on the recent data with IO plus BCG combination, where we have seen two positive trials. Crest, Susanne Lamab, which is to be administered for two years and Potomac, where Derville Map is being administered for one year. What we have seen is similar benefit, whether that's disease-free survival or event-free survival with hazard ratio of 0.68. For muscle invasive bladder cancer, we touched on EV Pembro combination, which is now the new standard care, regardless of cisplatin eligibility, given improved PATCR, which is with periop approach, and we are also seeing overall survival benefit here. On our end, we have to get comfortable with recognizing and managing some of the side effects that are associated with Enforge Map with Oton, that is Neuropathy, Hyperglycemia Rush. Rahul, what are we walking away with from today's discussion? Yeah, I am just baffled how fast things are moving here in muscle invasive bladder cancer. From GEMSIS to GEMSIS Derville Map as per NIGRE trial, and now the data around EV Pembro. During our discussion, we also touched on being in this data-free zone on what to do at the time of progression after Enforge to Map, and how to sequence our available options. I am hoping some real world evidence will guide our practice here, but right now it is important to acknowledge that because of these advances, we are seeing improved survival outcomes. Thanks for tuning in. Make sure to check out our other treatment algorithm discussions. We are the oncology brothers.