Bladder cancer treatment: The importance of accurate diagnosis and staging  

Ashish Kamat, M.D. Hello, everybody. I'm Dr. Ashish Kamat, professor of urologic oncology in the department of Urology here at UT MD Anderson. And I'm joined today by my colleague, Dr. Matt Campbell, who is associate professor in the department of GU Medical Oncology, and this is the Cancerwise podcast. Thanks for being here today, Matt. 

Matt Campbell, M.D. Thank you, Ashish. It's great to be here. And we have a very busy program discussing all that's new in the treatment of bladder cancer, so excited to join you today. 

Ashish Kamat, M.D. Yeah. You know, when we talk about bladder cancer theure's so much happening in the field, right? And we have patients that come here to UT MD Anderson, and, really, they are often referred to us with a diagnostic workup that's been performed. But oftentimes we get patients that come here and saying, "I think I might have bladder cancer." So, if somebody comes up front and says, I might have bladder cancer, what is the recommended workup for that patient? 

Matt Campbell, M.D. Most of the time, patients, when there's a suspicion of bladder cancer, it's either triggered by the fact that they saw blood in their urine, which is a common theme, or patients were found to have blood on a urine analysis. Clearly, there can be a variety of different issues that can lead to that type of finding, including infection. But this is the most common presentation. And then patients can have significant symptoms involving urination. This can be pain, or this can be having to urinate frequently. But whatever leads this trigger, often the next steps are imaging. And then a urologist, and you clearly can speak to this, will perform a cystoscopy, which is an evaluation of the bladder itself. And diagnosis is most often performed with a scraping of the bladder, which we call a TURBT to help us understand the staging and the characteristics that the pathologist is going to find. So, maybe, Ashish, you can speak a little bit more to your side when you get these patients to come in. 

Ashish Kamat, M.D. Yeah, absolutely. And you mentioned a key point: to come in, right? Because I just want to make a point that women, even today in North America, let alone other parts of the world, are often referred late to the urologist for a diagnostic workup when they have blood in the urine, because it's mistakenly attributed to other things, such as UTIs or even that time of the month, you know. I'll have patients tell me that. So, when we do a cystoscopy, we really use enhanced technology to look in the bladder. We're able to have higher-definition scopes. We can have what's known as blue light cystoscopy, but the TURBT is the first, most important step in a bladder cancer patient's journey, right? Because unless we get good pathology and send good tissue to the pathologist, they can't give us a diagnosis. I mean, if I don't give them a good section, they can't tell us if there's variant histology. They can't tell you if there's muscle invasion or lymphovascular invasion. And of course, all the research that we do, genetic profiling, etc., which I'll ask you about a little bit later, that depends on the quality of the resection. So, the first thing that we do, which is the resection as you mentioned, is extremely important. And in some patients, that's the entire cure, right? In non-muscle invasive bladder cancer, for example, if you take out the entire tumor and it's a low-grade tumor, that's it. The patient doesn't need anything else. But before I jump into low-grade, high-grade and muscle invasion, share with us a little bit about how do we grade these tumors? 

Matt Campbell, M.D. The grading is typically low-grade, high-grade, and then there can also be just carcinoma in situ, which is a noninvasive tumor on the surface. That is really one of the most challenging, I would say, areas of management. But this is telling us that whatever led to the bladder cancer, this tends to affect the entire bladder itself. And, you know, these are areas that the teams of urologists and all of those that are developing treatments for this are trying to tackle, because this problem is one where all of these cells within the bladder have the potential to develop an invasive cancer that can be life-altering and potentially life-threatening. 

Ashish Kamat, M.D. Yeah, I tell my patients all the time when they ask me what is CIS? What does it mean? Because in other cancers CIS is a precursor, right? It's not actual cancer, but in the bladder it's almost like, you know, the patient's got a backyard and there are a couple of weeds that they're seeing the actual tumor, but the entire sod is ready to form more cancers. Right? That's the CIS. And that's why the best treatment for patients with non-muscle invasive bladder cancer, unless it's low-grade, where we can just resect it and we're done with it, is immunotherapy and it's intravesical BCG, which is the oldest, most successful immunotherapy we've had for any cancer, let alone bladder cancer, really works well. And if it's done correctly, it has to be done correctly, as with any treatment, but if it's done correctly, patients have a 85-90% chance of not having any progression for up to five years, which is phenomenal, right? But clearly, we have about 10% of patients that will have a recurrence and may even have a progression. And that's when they get to slightly more advanced stages of their cancer. That's when I call you and say, "Hey, Matt, would you consider immunotherapy for this patient such as systemic immunotherapy?" Do you want to share with us when you might consider that? 

Matt Campbell, M.D. It is a moving target right now, and I've been very impressed. You know, when I started my clinic, we really had BCG and then we had relatively ineffective therapeutic options. And there has been an explosion of treatments now which can include systemic immunotherapy. And systemic immunotherapy, what we're trying to do is we're trying to give a treatment, and these are now, can be provided intravenously or at times, subcutaneously, to try to enhance the ability of T cells to both recognize cancer, and when they're interacting with cancer, not be shut off so easily. This is a big decision because these treatments do carry with them risk of major side effects and even risk of death with a serious immune type of toxicity. And the whole question, and this is why this is always a partnership with, with your team, is how risky is the cancer to the patient? How risky would potentially surgery be to the patient, and what is the goal of therapy? And if patients are very adamant that they don't want to proceed with surgery for their bladder, I think discussion of the risk and benefit ratio is very important with these new therapies, as a bunch of them are now combining local treatment with systemic treatment. 

Ashish Kamat, M.D. Yeah. Now, very good points. And you mentioned team. It's always teamwork, right? I mean, it's medical oncology, urologic oncology, pathology, our nurses, our patients, it's all one team. We here at UT MD Anderson did some of the, you know, pioneering studies when it comes to intravesical gene therapy for these patients that, unfortunately, have not been able to have a good, you know, success with intravesical immunotherapy. And we have all of them available, right? Now, there is gene therapy which is adenovirus. We have a gene therapy in development, which is an oncolytic virus. We have what patients colloquially will sometimes call a pretzel. It's actually an intravesical delivery of gemcitabine that's put in a little silicone-shaped device that's shaped like a pretzel. So, patients call it a pretzel. And then we have augmentation of BCG with IL-15 agonist and many other treatments that are being developed. But you know, again, we're trying to allow our patients to save their bladders because most patients want to save their bladders. Interesting though, that's what we thought. I'm sure that's what you think as well, right? 

Matt Campbell, M.D. I agree. I mean, I think most patients - I mean, bladder surgery forever in terms of cystectomy has carried with it, you know, risk of death within 30 days. That's not insignificant. And clearly, if you have an experienced surgeon in a surgery team like yourself and at MD Anderson, patients often do quite well. But historically, this is a very morbid operation, and patients carry with it, you know, changes in how they view their body, changes in sexual function, changes of how they're going to potentially interact for the rest of their life. And many patients are seeking ways around this. And I think as we're developing better and better treatment strategies within the bladder as well as systemically, more patients are realizing the opportunity to keep their bladder. I think we currently have seen tremendous strides, and there's clearly a bright future. So, you know, when patients come in and they're talking to you about removal of their bladder, what do you think are the, the things that they are most concerned about with that surgery? 

Ashish Kamat, M.D. I'm glad you asked me that, because, you know, one of the things that I've realized over the years is you've got to ask the patient, right? Ask the patient what matters to you. And I want our patients to tell us what matters to them, because sometimes a patient will actually say, "You know what? I'm older. I don't have the ability to drive back and forth to the hospital for multiple visits. My grandson or granddaughter can't really take time off to bring me for bladder preservation strategies once a week. Just take out my bladder and be done with it." You're like, "Okay." And we actually did a, and we were part of a multi-center study that was done through PCORI and asking patients this question. And amazingly enough, at six months to a year, patients who had had their bladder taken out, they chose that, of course, the patient had chosen to have the bladder taken out, had better quality of life emotionally, financially than patients who continue to come to the doctor to have intravesical therapy. So, we have to listen to our patients, right? It's very important. But once the patient says, "Yes, talk to me about bladder removal," it's very important that you understand what it actually involves, what it means. As you mention, it is a major, major surgery. We do a lot of it here at MD Anderson, but there are many places that do one or two a year. That's clearly not enough, in my opinion, to be good at that. Not just because the surgeon may not be good, but it's the whole infrastructure, right? It's the perioperative anesthesia. It's the fluid management resuscitation. But patients really that come here are told we do it on a pathway. It's very standardized. The surgeons here are excellent, you know, if I say so myself. And patients stay in the hospital roughly three or four days and our morbidity rate is extremely low in the first 30 days. But can it happen? Sure. When does it happen? Usually once the patient goes home. Right? When they're not being monitored closely. So, it's very important the patient has good support. If I see a patient as enthusiastic as he or she might be, but doesn't have good family support, doesn't have that ability to have someone look after them when they're home, I try to encourage them either to find that support, go to a skilled nursing facility, or consider something else other than radical cystectomy, which brings me to bladder preservation. Let me ask you: today, in 2026, what would you recommend or counsel to our patient if they said, "Hey, Dr. Campbell, tell me about radiation from bladder cancer?" 

Matt Campbell, M.D. I feel very fortunate that, you know, we have faculty in our radiation oncology group that are extremely passionate about this subject, and we have our radiation oncology team is virtually willing to see any patient that's interested in this strategy. We clearly have patients that are, I think, excellent candidates for this, and we have patients that are not ideal candidates. So, patients that are not ideal candidates tend to be extremely symptomatic. They're having to urinate every hour on the hour. They're waking up at night having to urinate frequently. And the chances of that improving with the bladder preservation strategy is, frankly, quite low. There's also patients that based on how their tumor characteristics, in terms of where it's located within the bladder, the size of the tumor, is it multiple tumors in the bladder? Do they have the carcinoma in situ component that we talked about earlier, are typically less likely to be good candidates. But to me, I think information and having multiple opinions from multiple different disciplines provides the best possible opinion. What I really love about working with our team is we are not a one-size-fits-all shop. There are patients that we think are clearly good candidates for surgery-based approaches, others that are good candidates for bladder preservation. It's trying to figure out and personalize that treatment for the patient that we see in our clinics. 

Ashish Kamat, M.D. Personalizing cancer care for patients is extremely important. And as you mentioned, radiation therapy for bladder cancer is an option, but it's an option for very selected patients because if it's used inappropriately, it can actually make things worse, right? Quality of life for worse. It can make the subsequent treatments difficult. So, now we've, sort of, organically, we've moved from non-muscle invasive to muscle-invasive bladder cancer. And today, I think in 2026, we have to admit and say that preoperative or perioperative therapy, along with either surgery or radiation therapy, is the standard of care, right? And that's been evolving so rapidly that sometimes it makes my head spin. So, you know, Matt, when I send a patient to you and the patient says, "Dr. Campbell, Dr. Kamat has recommended that I have my bladder taken out, but he sent me to you to discuss perioperative therapy," what are you recommending to our patients? 

Matt Campbell, M.D. Most of these patients are now muscle-invasive disease, and this field has shifted tremendously. You know, one of our professor emeritus at MD Anderson, Barton Grossman, really helped define neoadjuvant-based chemotherapy as standard of care. And this was with regimen called MVAC, which involved a drug called cisplatin. Cisplatin is very hard on patients' kidneys, very hard on nerves, very hard on hearing. And a cisplatin-based regimen became our standard of care prior to surgery for several decades. The challenge was about half of patients were never candidates for cisplatin, and in those patients, we were really left with either surgery or bladder preservation with chemotherapy, radiation. This is all dramatically shifted in the last year. There is a treatment with enfortumab vedotin plus pembrolizumab that has dramatically increased the chances of eradication of cancer at the time of surgery. And to put that into context, with cisplatin-based chemotherapy, we were achieving somewhere around 30 to 40% at best, of patients would have no cancer or be considered pathologic complete responses at the time of surgery. Those numbers are now pushing closer to mid-50 to even mid-60 percentage based on how you're doing your calculations. And this includes patients that historically were cisplatin ineligible. That has been a huge game changer for us and is now letting us dream to the future, which is: which patients can potentially avoid the need for surgery after therapy, but we still have a lot of work to do with ongoing studies to answer that type of question. 

Ashish Kamat, M.D. I want to caution our patients that are listening a little bit about that, right? Because the current improvement in overall survival that we have seen is when we look at the preoperative therapy, then the surgery, and then the adjuvant therapy, right? And we can't as physicians pick which part of this we believe more than the other. I think if you go into this with unbridled enthusiasm, trying to save our patients from a radical surgery, our patients will suffer. So, like you said, we have to study it. We have to look at it really carefully before we can recommend to a patient which one of them can avoid the radical cystectomy, but that's what we're working on. The other thing I often tell my patients, because, you know, it's remorse, right? If a patient undergoes a radical cystectomy and then on the final pathology, there is no cancer on the specimen, sometimes the patient may get disappointed, but that's actually a great result. So, I often tell patients, "Hey, you're going to get systemic therapy with Dr. Campbell. Then you're going to have your surgery, and I hope that when your bladder comes out, there's no tumor in there. Because that's what gives you the best chance of long-term cure." But today, as of recording this, this podcast, really, we don't have a reliable way to predict which patient has that pathologic complete response. We think we know it, right, with cystoscopy, cytology. Cytology is like shed urine cells that we look for a cancer, imaging, MRI or CT scan. We think we can predict who's going to hit that, but we can't really predict that. So, I always tell patients, "Listen, this is a package deal that is going to improve your overall survival." What do you tell patients when they come to you after I've put them through a major surgery, they're now recovering, let's say four weeks out. And they're asking you, "Dr. Campbell, my specimen. There was no tumor in my specimen. Do I still need this additional therapy?" What do you tell them? 

Matt Campbell, M.D. I completely agree with you, Ashish. One of the worst things that we can see for patients with this cancer is that their cancer has now spread beyond where it began, and they're still dealing with the tumor burden within their bladder. This, the quality of life for these patients tends to be quite poor, with concern for infection, bleeding and potential invasion into other organs, and avoiding that is, is critical. I tell patients it takes millions of cells sitting around each other to basically be a one-centimeter tumor, and our ability to detect that, even with our best current studies and even if patients undergo a repeat scraping of their bladder, is uncertain. So, I 100% agree with you that the advances that we have made to date with this strategy have involved surgery, and I still think surgery is a crucial aspect of this. 

Ashish Kamat, M.D. But again, we're always looking to the next frontier, right? And one of the things is, is capturing and measuring what we call minimal residual disease. We now have technology where we can actually take blood from the patient, look at their DNA, tumor DNA, and we're doing it here in the colorectal department. We're doing it in, in urology through the Guardian program, which is, the two of us are involved in, of course. But for our patients from a lay perspective, educate them a little bit on what is the ctDNA, what is this MRD? What does it all mean to them? 

Matt Campbell, M.D. Yeah, it's a fascinating space, and I completely agree. I think it's without question one of the most exciting arenas in our field. This is for, for ctDNA, we're looking currently at evidence that there are shedding of tumor DNA within the bloodstream that we can pick up in. And the current testing that we use is tumor-informed, which means that the company is basically looking at the tumor specimen, doing sequencing and picking out candidate genes that they're going to then follow. They're looking for that same genes within the bloodstream, and this is a way that we can actually track patients. And currently, you know, we are using it for patients at diagnosis of muscle-invasive bladder cancer, through treatment of muscle- invasive bladder cancer prior to surgery, at the time of surgery, and then following them in the post-operative setting. And that allows us to have a level of detail that previously we were relying only on, basically, radiographic assessment, which was not able to pick up microscopic disease like this testing can. Clearly, one of the exciting details that we saw this year at the genitourinary symposium was the emergence of urinary tumor DNA, which currently is still in development but promises, you know, a bright future and companion with circulating tumor DNA. So, I was hoping that you could also speak about the, the promise of urinary tumor DNA. 

Ashish Kamat, M.D. You know, that's a fascinating field, right? The classic way that we've looked at cancer in the urine is what's known as cytology, where we look at the urine cells and, you know, the pathologist sees is it cancerous or not. Unfortunately, pathologists aren't trained in that too well nowadays. So, we have to rely on molecular testing, right? So, we've used what's known as a FISH assay where we look at certain chromosomes: 3, 7, 17, 9p deletion, that for the last 10-15 years, and again, we did some of the studies here almost 20 years ago, has a very strong predictive ability to detect residual disease in the bladder when none is visible to us on a cystoscopy or imaging. And now with utDNA, hopefully, we can take that a step further, right? Because now we can have a very, sort of like a boutique test that is specific to the patient's tumor rather than the pathogenesis of bladder cancer, which is what the older tests were. So, I'm really excited about combining ctDNA, utDNA imaging, all of this to see where we can go next for our patients, how we can try to help them spare their bladder. You know, Matt, this is such a great field and a good place to be in for us and on behalf of our patients right now, that we could talk forever, but we obviously can't in the interest of time. Any closing thoughts you want to share with our patients about what's happening today? What's going to happen in bladder cancer in the next six months that you're most excited about? 

Matt Campbell, M.D. To me, I think where you go for treatment makes a huge difference. I think having a team that has clear confidence in use of currently available technology, having a great surgical program, having experienced radiation oncologists and having the ability to offer best care for the patient in front of you in true personalized fashion is critical. I am very excited about the next wave of trials with the premise of how can we best define who does not potentially need surgery but do it in a very safe manner. And just like you brought up earlier, this huge improvement in non-muscle invasive bladder cancers, I think is going to trickle into our field of muscle-invasive bladder cancer. So, in patients where we eradicate the life-threatening component to it but may be left with non-muscle invasive disease, how do we best address those patients and how do we finish off the job? So, it is an exciting time and working with people like yourself makes our job much, much easier. And I think it's helping us make tremendous progress working across disciplines. 

Ashish Kamat, M.D. And Dr. Campbell, thank you so much for joining me today. This has been a great conversation. 

Matt Campbell, M.D. Thank you Dr. Kamat. 

Ashish Kamat, M.D. Thank you so much for listening today. If you enjoyed this episode, be sure to follow or subscribe on Apple Podcasts, Spotify, YouTube, or wherever you get your podcasts. And don't forget to comment or review. For more information or to request an appointment, call 1-877-632-6789 or visit MDAnderson.org. Thanks for listening to the Cancerwise podcast from UT MD Anderson.