Ep. 310 Bladder Cancer Risk Stratification: Best Practices with Dr. Sunil Patel and Dr. Kristen Scarpato

This week on the Backtable podcast, my youngest bladder case, her patient is 21. Yeah. And it, I just kind of, how many years am I going to, when am I going to feel comfortable saying you're okay? Now she's a couple of years out now, so I don't have to answer that today. But she will finish her five year surveillance before she turns 30. And that's the patient. I don't see. I probably would not feel comfortable stopping surveillance, right? I think, I mean, there's something about your biology or your exposome, right, that you created this cancer, right? At that age, I would not feel comfortable stopping surveillance. And I think that's where, again, this whole, like, guidelines are good framework, but they're not perfect, right? And it comes down to the person that's sitting in front of you, the patient, right? And then you got to figure that out. But it is, it is a little unsettling, the rates were seeing this. Welcome to Backtable, I'm Bob Donishmett. And today I'm so excited to be talking about one of the most deceptively challenging parts of non-muscle invasive bladder cancer care, risk stratification. Everyone says they do it, but when you look under the hood, the biggest errors often happen before treatment even starts for a patient. In the pathology assessments, in how risk groups are assigned, how much risk is being tolerated by the physician or by the patient, and then downstream consequences show up as overtreatment, under treatment, or surveillance that doesn't really match the biology. So I'm very excited to be joined today by Dr. Kristen Skarpato, associate professor of urology at Vanderbilt University, and Dr. Soniel Patel, assistant professor of urology, and Johns Hopkins University. Thank you so much for joining me. Thank you. Thanks for having us. I'm going to start firing questions at the both of you because there's so much to get through. Let's get into it. Kristen, what do you think are the biggest challenges with risk stratifications that clinicians get hung up in? Yeah, that's a great question. There are a lot of challenges associated with risk stratification. I think one of the biggest challenges pertains to intermediate risk disease, and we've seen a lot of excitement discussion about intermediate risk disease in the past couple of years, particularly with different risk stratification systems. But I do think that that group, that category, can be the most challenging. If you have a possibility of a patient with high grade, a possibility of a patient with low grade, there can be multi-focality recurrence. This group is really heterogeneous, and so I think for those of us in practice managing patients with bladder cancer, do we treat them with postoperative intravascular chemotherapy? Do we do induction? And is it induction immunotherapy or induction chemotherapy? And then are we doing maintenance in which patients? And I think because of that heterogeneity, the practice patterns are really not uniform, and patients have various or variable outcomes because of that. So that bucket is the most, I think, stressful for urologists in terms of patient management, and that's still one of the biggest challenges we have. Absolutely. I mean, you've really laid the groundwork for everything. We're going to be covering today, so thank you for that. Now, Sunil, from your perspective, right, what Dr. Proto is saying is, everything's kind of grounded in the past, and how are you going to define this patient? So with the pathology, what do you think most strongly changes management? What are you looking at that frames how you define the patient in the population? No, no, I think that's a great point, and when we talk about the pathology, we're really looking at the grade, right? I think the low grade, high grade really is probably, in my opinion, one of the biggest kind of defining factors in this intermediate risk group, and I think sometimes it depends on the heterogeneity of the pathology read, but sometimes we see these patients with this mixed low grade, high grade, right? And I think from practice patterns, right, like Dr. Proto said, that some, the clinicians vary in their kind of how they treat this, these patients. So you may have a patient that has like a 5% high grade, but mainly low grade. How are you going to treat that patient, right? And that's, we don't really know, right? And I think it's just how we've been taught, but then also, are we really calling that patient a low grade, even though there's a 5% and if you had 10 different pathologists read it, are they all going to call it the same, too? And then that adds the question of how many second reads are we going to get to? So I think the pathology is really important, and I think, I mean, even our guidelines state that sometimes we're mainly with varying histology, but you should have an expert pathologist look at these. And I think that really helps us when we're kind of defining these patients and when we like, okay, you are this risk category, but when it comes down to the grade is so important. So we're all fortunate to be practicing in an academic setting. Is it built into your practice that everybody gets a path over read when they come to you? If you didn't do the resection, somebody else did it. I see everybody's heads nodding. Yes. Yes. Yup. And what are you finding as the differences, most of the time, if your pathologist over reads the sample, and it differs from what was initially build? What are those differences that you feel like your GPU path, pathologists are catching? Certainly variant histology, not always seen on the outside from the outside hospital. So I think that our pathologists are much more in tune to identifying variant histology. And then as Dr. Patel alluded to that, that focal high grade, I think that our pathologists are good at picking that up, which can be clinically challenging for us to manage, as he said. And then what about CIS, do your pathologist always comment on CIS? Do you find that that's standard practice for your team? Because that's something that I see oftentimes, somebody comes in and it just says, "High grade TA." And then my path over read will say, "High grade TA and CIS." And I'm like, "Oh, that's important. That's important for trials, important for implications." That's something that I've been bumping into. Correct. I think our pathology group, our bladder cancer pathology group specifically, comments on the CIS, because as you alluded to, there are so many ramifications of having high grade T1 with or with that CIS, right? I mean, I think it's very important. And again, to that change that we see, I think we kind of looked at this as well, especially with the variant histology, like Dr. Skarpon mentioned, it's really important. And one of my colleagues, Dr. Maskeits and our chief resident, Dr. Tony Sue, just published a paper and showing that variant histologies are being called more and I think more centers are where we're getting more and more second reads with these expert pathologists and that I think it is leading to better care for patients. But we do see a change in about probably 5% to 10% of our pathology. And most, I would say, the vast majority of time, they're consistent, however, there are elements of change, 5% to 10%, it's a good number. So, I mean, that's a significant number of different pathways that the patients may be calling on. Correct. Yeah. Importantly, too, I'll say that we also see changes in staging, you know, from this patient on the outside came in with high grade, you know, muscle invasive and then we downgrade or vice versa. And so I think that obviously is a hugely important distinction because that really changes management. Absolutely. And that actually feeds right into my next question for you is what are you seeing that really changes your idea of a patient from intermediate risk ish to high risk versus very high risk, maybe. What are you looking for? Yeah. I think we're looking at what prior therapies the patient had, if any, time to recurrence, is someone who recurred at first cystoscopy or first to your BT or was there a long interval of time without any bladder cancer, the pathologic features like CIS, like lymphovascular invasion, any variant histology, those types of changes certainly can bump someone up from an intermediate risk into that high or very high risk group. Absolutely. And I just want to ask from a purely logistical standpoint, in your note, when you're describing patients, do you put a risk group on the patient in your note, like your assessment is this is a so and so patient with blank risk or not really, you just say NMIBC and kind of move on. We use dot phrases and I think we do a nice job importantly because it really has implications for patient care and also makes it easier when you're going back and seeing this patient in follow up because this is often a chronic disease and something that we're managing in the long term. So I think it's really critical to say what the patient's risk stratification is and include the imaging, the timing of cystoscopy, results of any biomarker tests, all of that should be included in the assessments. And obviously the IBCG risk groups were recently incorporated into NCC and guidelines. Has that changed anything for you or has your risk definition always been, you know, high-grade as high risk or are you always looking at number of risk factors or were you in the AUAID bucket where this is in the middle basically? Yeah. I think a lot of what I do is very dogmatic but not necessarily for non-muscle invasive bladder cancer because it is so heterogeneous. I will say my personal practice has always been to include high grade as high risk. I think it's a different pathology than low grade. But I think the incorporation of the IBCG risk group into NCCN is helpful and helps me and hopefully others be more thoughtful about those risk factors and what that translates into in terms of a patient's need for additional therapy or how we might survey that patient in follow-up. So yes, high grade to me is kind of high risk. And I think considering a patient's age and number of recurrences and all of that is really important. And Dr. Patel, when you talk about this to patients or maybe to your trainees and general, do you use any risk calculators? Do you plug something into your smart phrases in your notes? Or is this more of a Gestalt type of situation? I would say a little bit of all of the above. So we do formalize our notes as well, right? We do risk ratified patients. I think it's very helpful when you're following patients five years from being like, "Okay, this is the original diagnosis." But when we're talking about the risk calculators, I think there's the ERTC-1. I think Beacon does have a lot of good handouts as well. And I think that's another part in terms of when we're talking about risk stratification and helping patients understand it as well. But lastly, I know you and I were chatting about this earlier. But Laura Bukovina just published a nice paper in BJIU, I believe. And making kind of simplifying the risk categories and kind of just looking at certain factors and showing low, intermediate, and high. And so I think that's a great paper for you guys to get a chance to look at it. But that does help, I think. And now that that paper is recently published, I think that will be kind of used more and more. I think just simplifying this, basically, so that every clinic visit doesn't become into a lecture for the patient. And you can give them the pathway of this is where you are. This is the spectrum of the disease. When you're here, this is what we do. If your disease moves to this bucket, this is what we do. Let's keep your disease in this bucket. And we never have to talk about those things, right? Trying to make it as easy as we can. So you mentioned assays earlier and kind of clued us in towards the next step. So where do urinary and genomic assays actually help? I kind of feel like sometimes they add data points as opposed to adding value to the patient's treatment care. But at the same time, we're all excited about having this data. So academics were certainly, this is our place to shine and learn and push the envelope. And I get that. I order a lot of tests that I don't always know exactly how to translate into real decision points versus conversations more to get the patient to prepare for next steps in advance. So signeterra, Vesta, decipher bladder, FGFR testing. What are you guys using, if any, and in what scenarios? Yeah, I mean, I think getting back to your kind of initial question there about who we're using them on. And when it's, you have to really be thoughtful about what is the patient population? Is this an at-risk patient population who you're concerned about a possible new diagnosis of bladder cancer? Is this the hematuria population where you're trying to determine if a patient would benefit from cystoscopy or not? Or is this already a patient who has bladder cancer? And you're looking for recurrence or trying to assess response to therapy. And so kind of understanding what population you're using the test in. And then is it prognostic? Is it predictive? You know, who was this test validated in? There is a lot of excitement. And I think it makes a lot of sense to try and use these tests. You know, bladder cancer, the urine comes in contact with the urethelium. And so having some sort of signal shed into the urine, it makes a lot of sense. But I don't think as guidelines have kind of universally alluded to that any of them are fully ready for prime time, replace all cystoscopies. And I just think we need to be very thoughtful about it, where I'm most commonly using them is in the hematuria population. But certainly we have some tests available now for surveying patients who have a history of bladder cancer and looking to their response to therapy or actually, what is the likelihood that they will respond to BCG in their high risk group? So just for our audience, let's be specific because I think it's helpful to frame it. I love your framework of what part of the disease process are they in? And what is the test trying to give me here? So for the hematuria population, right, you're trying to figure out do I need to do a cystoscopy or not? And so for the microscopic hematuria population, I use CX bladder in that setting, I find that it helps, especially my VA patients where they're traveling from far away. Sometimes that's really nice to say, do you actually need to come in for a cystoscopy or not? I'm not routinely using it to replace a cystoscopy, but occasionally a situation will arise where a patient misses their cystoscopy. And there are eight hours away and you're kind of thinking, do I make them drive? Do I send them a kid? I know that during COVID, there are folks who published on using them in that space, even though obviously the tests were not necessarily validated for that purpose. You guys using anything to replace a cystoscopy or no? No. I would say no as well. And I think getting back to this biomarker assay test and kind of being thoughtful about who we are using it for, right? Because as we alluded to, this is not part of guidelines, right? So I think that's where I think it's really helpful to understand where you may see these benefits, right? So the FGFR testing, right, that patient who has that mutation, they may benefit from Irnuffinib, right? I think that's a person with this kind of recurrences. So the patient that has a lot of recurrences, that's the person that you maybe want to use that test for. So what tester you order using to get FGFR data? Well, I so I personally do not order that. So, but I think that's where the benefit is for that patient. Like I don't think it's for every single patient who has high risk disease or for patient who has grossing maturity or patient has just a new diagnosis. I think it's good for that patient who has recurrence. Sure. Low grade recurrence is trying to figure out treatments. Correct. So then you talk about decipher, right? Specifically for decipher. Then you have these patients and I think that test is really good for patients who have luminal versus kind of the other subtypes. And understanding that luminal tends to have a better prognosis. And so the other subtypes potentially have worse. So that patient who has that high grade T1 or has that recurrence, like, hmm, let's see, are you going to really benefit or are you just going to keep on having these recurrences? Are you mean that that catcher like that 25 to 30% group that just recurs, right? And it is important to find out that I think that decipher test is designed for invasive tumors. So high grade TA, you can't send it for, it's not designed for that. It's got to be that T1 population like you mentioned. Yeah. And then I think the Valar for the BCG is actually a pretty unique and cool test. I know you and I were talking about this earlier and I think it's, it really helps us understand is BCG going to be helpful in this situation? And I think one thing about non-musical invasive bladder cancer and these patients that we often forget to talk about is how the detriment or the crippling of bladders that we do, right? And sometimes this repeated treatment and if you have a test like this that could potentially add some insight into is BCG going to help? So you're talking about the Vesta chai biomarker for prediction of response to BCG versus a chemotherapy. Correct. Right. Yeah. And I think that that's where that test is potentially beneficial, especially if that patient who comes in is already their IPSS score and their urination symptoms are ready through the roof, right? And you're like, all right, BCG, I'm not sure if it's going to work, but maybe that person's a good that person's a good, I want to get that test on. And then the signeterra, I think often a lot of us are using an MIBC situation. Then the NMIB situation, I think it can be helpful for determining if you're at high risk for progression. So that patient who has like the high grade T1 with CIS, like something about your pathology or your bladder, right? We've seen those bladders where it's not just a one tumor. It's like the whole bladder looks like can't cancer yet, right? Like you're susceptible, but we're reflecting your whole bladder and are you someone that's just going to progress or recur? And we're going to have residual disease that person may benefit. And then lastly, there are these other tests, right? There's some of these new urinary biomarkers that look for residual disease, right? Honestly, I would say I'm not the biggest fan of that because I think a lot of us, we've all been taught that a very good TRBT is usually at the basis and the standard of care for patients with NMIB scene. I think we can patients benefit from a very good TRBT. And I think this residual disease, this urinary test, I'm not sure how much application it has, but I think that's another person where you may think you, you've received everything. They may have a little bit of CIS and you're just like, do I need to check to see if they have residual disease or not? Do I need to go back and again and do another resection before doing intramuscal therapy? I think one of the challenges, at least for me, is that a biomarker feels objective. It feels like you get an answer to something. And so we probably overvalue them a little bit based on that aspect of it. Maybe more than the evidence with support because like you mentioned earlier, we don't, they're not always validated exactly for the population that we're using them for. And so you can get into the situation where you have a little bit of a disconnect where clinically bladder looks good. And you get your cytology and your cytology is, we're not going to get into it. The cytology here, but let's say your cytology is fine. And then you get some urinary biomarker test back and it says there's something there. What do you do with that? Do you try to intensify your approach to the patient? Do you trust your visual assessment? I think there's something to the fact that these biomarkers are probably detecting disease earlier than we're able to visualize it. I believe that just knowing how imperfect or visual sense of a bladder is on a screen, but I don't know how to treat a patient in that way. Because I have what I'm looking at and what do you do? How do you handle these situations? It's such a fascinating question and I agree 100%, it's a problem I think we're going to encounter as we see more and more of these kind of high tech tests that are becoming available and it's exciting, but I don't think any of us know what to do in that situation. And I think we have to consider our thoughts on it and then the patients thoughts on that I always like harken back to the the memorial study that looked at patients with a history of bladder cancer who were surveyed on their willingness to accept a biomarker in place of a cystoscopy and almost 100% of the patients in that population said that they need a test that's going to give them like a 90% assurance. 80% assurance that there's no bladder cancer being missed. Most of them said actually 95% is preferable. So it's what we trust. It's what the patients trust. And honestly, there isn't an answer right now. And we have cytology and the history of of that to kind of go on. What do you do with a patient who has a positive cytology, but a negative cystoscopy. And I think that's an area where enhanced endoscopy comes into play and making sure that you're getting the thorough look of the bladder with you know, whatever enhanced endoscopy system you're using and looking at the prosthetic urethra and assessing the upper tracks. So being really thorough, but beyond that, I'm not sure that it could change our management yet. Are either of you using blue light in the clinic or just in the operating just in the upper room. And I think to get back to Dr. Scarport's comment, which I 100% agree with is the conversation with the patient, right. I think we've all had patients who come from different kind of medical or see health literacy, but also different thoughts and views on their bladder cancer as well. And how aggressive they want to be. And I think this is where being a clinician is almost like and about blend of art and science for that specific patient, right. And it's these constant communications with our patients were, hey, what do you lose to? But kind of what's like, you have the cytology or you have this, you can't see anything on Sisto, your CT scan, you've done the upper tract imaging can't see anything. What are we going to or are you just going to give you BCG? Are we going to just give you Jim Dosey or some sort of treatment. If we can't see and what are we going to follow it, then are we just going to follow this test. And then. So I think it's one of those situations where I think we just had to be very thoughtful and listen to our patients. I mean, I think by having these adjunct tests, they may help their their ad value, but I don't think it can pull away from the cystoscopy or pull away from cross sexual imaging that we need to do. So let me get back to just a little bit more basics going back to intermediate risk as we talked about. This is a very heterogeneous category. So when you're looking at a patient to intermediate risk, let's say low grade intermediate risk, so recurrent paper. What is your adjuvant therapy in those cases? What are you using? Are you using single agent chemo? Are you giving BCG to those patients are using double agent chemo? Let's start with you. Low grade, I use gem site of being intravascular gem site of being high grade. I use BCG if available. Unfortunately, we've been in a position to have BCG a pretty regularly available. You guys are very lucky. The rest of the country. I think isn't a slightly different situation for sure. And what about you? I would say the exact same thing low grade, but we do gem site of being in dosataxle. You often do double agent for in for low grade as well, but high grade, I agree. I fund to integrate low grade and high grade, high grades of different disease. And I think you can't really treat that same way. But then the BCG shortages, right? So then obviously extrapolating based on pre-lum data and hopefully the bridge study, max cases study comes out soon. So then we can see it's benefit. Hopefully in the high risk patients. But yeah, often with the BCG BCG shortages were often left with double agent. So then if you start with your intermediate risk patient gem site of being a year later, they recur on that. What's next? They recur with low grade within a year. Yeah. Yeah. That's a that's a tough one. I probably would try a doublet therapy in that setting before I would go BCG. Okay. So stick to chemo for as long as you can. I would. Yeah. And then I would really make sure that the resection was complete. And we may talk a little bit more about that. But that's a hill I will die on. I feel very strongly about equality to you, RBT. And you need to make sure that what you're seeing is. Is a recurrence and not a persistence. Yeah, that's a really good point. And I feel like sometimes with an early recurrence on the anterior wall, you kind of get this idea. Was this tumor? Has it been here? Was it here before? And nobody noticed it. Or did it really truly just grow back within a three month window. Yeah. So in that scenario, where you have your intermediate risk patients, you're talking to you, RBT. I still do a lot of TRBT as well. Are either of you incorporating non-TRBT based management? Are you using intravascular chemo in lieu of a TRBT? Have you guys done the story yet in your practices? We just did our first patients this past week, actually, how to go. And it went really well. Awesome. Yeah. It went really well. Really well. Yeah. So we've, we have probably four or five patients recently, we put it on it. I am still aggressive with my TRBT in that situation. And we'll still give this a story afterwards as well. Are you using it, adjuvantly? Yeah, correct. For our patients, especially it depends on the volume. If it's like a tiny little tumor right fine, like you see on scope, usually we're still just falling in the system. Again, then giving them some story. Adjuvantly though. Yeah. Interesting. And how do you guys, how have you been deciding to incorporate that management strategy versus OR? I mean, you're doing it adjuvantly, so I'll direct to you. I mean, I think it's very patient specific, right? The goal is to try and avoid an anesthetic in this older sicker patient population with low grade tumor that can be ablated with this therapy. And so I think we're really being patient specific and trying to identify which patients would really benefit the most from avoiding the anesthetic. Yeah, I mean, I agree. I think it's usually the patients with anti-coagulation patients. You don't want to take to the operating room. There's certainly a role for it. I'm not convinced that it'll move into the first thing we do is a blade. If that doesn't work, then we're going to resect. I think there's always going to be patients. We're going to want to take straight to the operating room. But using it adjuvantly is an interesting approach. And I think we'll probably see more and more people do that is we're still using chemotherapy in that adjuvant space as well. So when you have these intermediate risk patients, I kind of feel like I'm either going to overdo it or under do it, right? Sometimes you're really trying to find that line of deescalation, vulgarate things in the clinic, maybe not put them through more versus am I missing something? Is there a problem going on here? Is there disease in the prosthetic erythritis just coming from the upper tract? How do you find that balance of not over-surveiling, but also not missing anything? Do you follow standard pathways? When do you change things up? When do you try to escalate versus deescalate? And let's say we're excluding the elderly patient on oxygen where it's purely patient specific. Yeah, I like guidelines and I like flow charts. And I would say in general, I try and follow that. But you obviously have to be very thoughtful about the specific patient that's in front of you. And oftentimes the cancer itself will tell you how to declare itself. Yeah, declare itself. You know, do you need to escalate or deescalate? I am trying to deescalate as much as possible. And I'm happy that there seems to be a push to do that, because especially in this patient population that are so heavily treated, the quality of life consequences are really significant. And especially for those low grade intermediate patients, I think that there really is a role to deescalate. One of the questions that I have and I think many of us kind of struggle with is the long-term follow-up. So that you have guidelines. And it tells you, you know, like after five years for the low grade and then, you know, out to 10 years. And again, this is like the patient has to be comfortable. You have to be comfortable. I just saw someone recently who had if she's kind of a young female who had low grade TA in 2013. And she's transferring her care to us. And it's she still wants her yearly cystoscopies. And in my mind, it's like, you haven't had her. Her parents like this feels like maybe we could deescalate. But in that situation, the patient didn't want to. And then you have other patients who have high grade disease and are high risk, but haven't had recurrence for eight, 10 years. And, you know, I don't feel comfortable necessarily stopping my cystoscopy and that. So I think that that group can be really kind of challenging. And there's probably a lot of variability and how long we follow patients. Yeah, I feel like I'm going to have to start making some of these decisions soon. I've been in practice for five years. And so so far, everybody's been on surveillance. And now it's, it's coming to me where I have to start thinking about whom am I going to start letting go. And am I just going to go to every other year to make myself feel better. And then you're getting outside a guidelines territory. Yeah, I think the guidelines are very helpful because they do provide us a nice framework. And so when we all have patients who are 15 years out of their diagnosis. Right, zero occurrences, don't great, but they're like, so next year like, let's pump the brakes. And sometimes they're like, well, I was once told I have to do it for the rest of my life, right? And sometimes we see patients from community areas and then where I go, well, these are our guidelines and I think we can be thoughtful about this. I mean, the statistical odds of you having recurrence this far out, yeah, but I think it's challenging now too with our population and especially our elderly population, people are getting older and older, older, right? But then we're also seeing patients at a younger age. - You're seeing that too. - I'm seeing you. - Okay. - And so that. - Well, we're not all going crazy individually in our own settings. - No. - I have, my youngest bladder cancer patient is 21. - Yeah. - And it, I just kind of, how many years am I gonna, when am I gonna feel comfortable saying you're okay? Now, she's a couple years out now, so I don't have to answer that today, but she's a little finished her five-year surveillance before she turns 30. - Yeah. And that's the patient, come on, I'll see. I think, I mean, there's something about your biology or your ex-posome, right? That you created this cancer, right? And then you gotta figure that out. But it is a little unsettling. The rates were seeing this. - So I'm gonna ask you about upper tract surveillance. So when I have high-grade patients, if they have a recurrence, I'll survey their upper tract at the time of recurrence. That's kind of my threshold, every recurrence I do. And then I try to make sure, at least every other year, every couple of years, for low-grade patients, you know, maybe less aggressively so. So when you have these patients that are far out, intermediate-risk, class recurrence five years ago, are you still good checking their upper tracts every other year? I'm not. - Yeah, I would say very similar, yeah. - So when do you, what is your schedule? Just for our audience to give them a framework or what are you doing? - Yeah, at the initial diagnosis, everyone gets their upper tract imaging. For the low-grade patients, I am not routinely surveying after that. For high-grade patients, I'm close to that kind of every other year, unless there's a recurrence or like a cytology that doesn't match up with what I'm seeing in the bladder, but the rates of finding upper tracts in that setting are so low that I think after your kind of initial check, you don't have to do it every six months or every year, I think you can spread it out. - Yeah, I think it's a lot of scans for these patients. - Yeah, I would say every other year for these high-grade patients or at any recurrence, I definitely think any time a patient has a recurrence, the clock resets, right? - Yeah, for sure. So we've talked a little bit about guidelines and how helpful they can be for us, but also for framing things for our patients. But we all know we're not doing this perfectly, right? We hope the field is gonna change in five years. We hope we're gonna know more in 10 years. We hope we're gonna have no bladder cancer by the time we retire and leave nothing for the future generations. But I wanna ask you to think about this. What is it gonna take for us to learn to really move the needle? What do you think we still need to know? Pathology-wise, biology-wise. What do you think people should be studying if you had all the money in the world to throw at non-Muslim-based bladder cancer? What do you wanna learn? - I wanna learn how we can do better T-R-B-T's. I think that the fact that we still have for the most part rigid instruments and really limited tools, I'm excited about that. And whether it's like on block resection or using robotic arms or finding ways that we can assess depth interoperatively, however that may be, so much of bladder cancer quality care comes down to T-R-B-T. Like, can we see where the cancer is and what the extent of this is? Can we appreciate our depth and can we have instruments that allow us to manipulate cancer in a distensible sphere? - That, to me, is like what I would love to see in the future. - I mean, it's crazy to me to think how many cancers there are in the body and how many do we remove piecemeal the way we do bladder cancers inside the bladder? - Yeah, I think that we're so limited by that. And I'm excited that there are engineers, including one of my colleagues who's working on surgical robots to allow us to have a little bit more degrees of freedom when it comes to resection. But I think that impacts patients' recurrence, which impacts their risk stratification, which impacts response to therapy, and that's where I would, if I had all the money in the world, so that's what I'd love to see improved. What about you, snail? - Well, I'm gonna take another different angle, knowing all the work that I truly care about environmental courses and agendas. I think I'm in that school of thought, or if we can prevent it, then we should do better. I mean, I think, so 50% of bladder cancers are caused by smoking, right? The smoking rates have dropped significantly since the 1940s down to only about 10% now, where I was about 50% back then. So if we can highlight those other patients who are developing bladder cancer and figure out what is causing that, I think that's another, if I had all the money in the world, I think if we can prevent bladder cancer, that would be a huge win. Like you said, that'd be the best win at the end of our careers. If we can have reduced the incidence of bladder cancer, that would be a huge win. I think that's what I would do. But. - Please do it. - Yes, I mean, sold. And you alluded to risk stratification again, kind of coming back to this. So many of the categories that we put patients in, to me, don't feel biologic, right? So we define things as BCG unresponsive, BCG exposed. This is a response to a treatment that we have, that we sometimes have in good supply and sometimes have in poor supply. What do you think needs to change about how we risk stratify patients to actually allow us to treat the biology more than the drug definitions? - That's a really hard question. I do like what the BCG group has done. I think our intermediate risk stratification is just far too heterogeneous. And even the fact that we have two risk groups, you know, you have fewer buckets, you're gonna have more heterogeneity. And I know that in Europe, they're using grade one, two, and three. And so at least, you know, adding that third bucket, I think gives you a little bit more information about the biology. But if we could understand more, the risk associated with the way that patients cancer looks under a microscope or what, you know, methylation flags it's waving, I think that will be really helpful. But right now, we're kind of limited by that. And I think that that contributes to the heterogeneity. - Yeah, and I think getting to kind of just picking back off, I think that's 100% spot on. Like it comes down to that tissue, right? From that initial staging. And I think we could do better in that. And I think with newer tests, such as some of these ones that we mentioned. But even, I mean, we've seen AI kind of in pathology and histology kind of really ramping up right now. I mean, if we could leverage that to better understand and look at the tissue under the microscope and understand, is this the high grade that we always think, or is this something different, right? I mean, so I think if we did a better job of understanding from day one, how are we gonna treat that patient? I think we'll do much better. - No, I agree. I think this field is really wide open. And I'm really looking forward to seeing how it advances and how we can translate that to improving the way we approach each individual patient, improving outcomes. I think we have a ways to go. So we're gonna start wrapping up. I really wanna hear from both of you, what is one clinical pearl you wanna leave our audience with? What do you think they need to start incorporating into their practice? Maybe something you've learned that you think has helped you frame the way you approach these patients, whether it's in risk stratification, whether it's in treatment, whether it's in counseling, what do you wanna share with our audience that you think can help them take care of these patients better? - I want you to go first. I was just gonna say, you know, I've been kind of speaking up first. - Oh, no, no, no. So I would say, not to steal your thunder, but the TRBT, I love that. I love that pearl. I think that is one of the best pearls. But one thing I learned a lot in the last four or five years is really listening to our patients too, understanding how to take care of them. But I would say a good TRBT, getting a good pathology read and understanding what type of bladder cancer you're dealing with, right? And this risk stratification does help us a lot, and it's okay to call for help and ask a partner, like, hey, what do you think about this situation? I think sometimes, I know we often do that with amongst each other. We have a great tumor board as well, but I think when you have this patient who's not following the normal trajectory, where you think, I think that's when it's time to escalate. And I think that's a good pearl. I think a lot of people do that. And I think that clinicians in the community, you're all just in the community are doing a great job. They're asking for help. And I think that we're seeing that bladder cancers patients are being taken care of better, I think in modern era, because we have at our big centers, I think we have a lot more resources and we have those expert pathologists. We have us who kind of see bladder cancer day and day out. So I think those are kind of some of the pearls I would leave the listeners with. - Kristen. Yeah, I'm never gonna let you go first again. Thanks for stealing my idea. I'm gonna say communication, because this is a really special patient. population who will be subject to a number of different interventions and tests and imaging modalities and hey we have this biomarker and oh guess what this drug was just approved and I think it will be really critical for us to make sure that we are thorough in our communication with our patients using whatever aids we prefer whether it's you know urology care foundation or beacon or looking at nccn together to say this is a really exciting time in bladder cancer and you know guess what we're going to go to the OR and you are going to have a blue light cystoscopy but you know what that means you have to come in early and you're going to get a catheter beforehand when you're awake in the preoperative holding area but just being like really thoughtful and deliberate in our communication so that they know kind of what's coming next and it helps with the journey because it truly is a journey as you know they're navigating this disease which fortunately has so much excitement and energy and development and kind of a lot of novel things happening right now we just have to be really communicative. I think those are both really really great points thank you so much for the discussion I think I'm really taken away from both of you that better risk stratification better outcomes is isn't just about adding more tests it's going back to the basics getting a good to you RBT really being certain in the pathology of the tumor applying the guidelines frameworks consistently and then trying to translate that into a pattern of surveillance that the patient can really get behind and communicating all that to the patient all all the steps along the way so that they know they have a partner in the journey. Thank you both so much I learned a ton from you I know our audience did too. Thank you. 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