Bladder Removal or Preservation? New Answers Emerge

June 22, 2026

Transcript

Voice over:

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs:

Hi, I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for, by, and about the bladder cancer community. I’m also a survivor of muscle-invasive bladder cancer, the proud owner of a 2006 model year neobladder, and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, producers of this podcast.

I’m pleased to welcome today’s guest, Dr. Angie Smith. Dr. Smith is a urologic oncologist specializing in bladder cancer at the University of North Carolina School of Medicine and a leading researcher in patient-reported outcomes and pragmatic trials with multiple NIH and PCORI-funded studies, including CISTO, which is spelled C-I-S-T-O, the subject of today’s podcast. At the University of North Carolina, she is professor of urology and serves as senior associate dean of Faculty Affairs and Leadership Development and as vice chair of Academic Affairs in the Department of Urology. She has held key leadership roles in the American Urological Association and serves on the board of the Society of Women in Urology. At BCAN, she serves as a scientific advisory board member, received the Advocacy Network Award in 2019, and co-created the Patient Survey Network. Outside of work, she enjoys time with her husband Patrick and their two daughters. Dr. Smith, thanks for joining our podcast.

Dr. Angela Smith:

Thank you, Rick. Thanks for having me.

Rick Bangs:

Our pleasure. So you and Dr. John Gore, which many of whom, many of our listeners may know, you wanted to explore bladder preservation versus radical cystectomy, and you jointly led this CISTO study. So what does CISTO stand for? What were the questions you sought to answer and to which patients is this important work relevant?

Dr. Angela Smith:

CISTO stands for Comparison of Intravesical Therapy and Surgery as Treatment Options, so C-I-S-T-O. The study was born out of a Bladder Cancer Advocacy Network think tank, which really joined patient perspectives with the bladder cancer research community, and the knowledge that this question of what is the best treatment for specific types of patients facing recurrent high-grade non-muscle invasive bladder cancer was the right treatment for them. And really simplifying those treatment options, it’s either having the bladder removed, which is a major surgery, versus having bladder sparing therapy, and there’s a really wide and increasing range of options in that category. It was born out of a need by patients, and I’d say providers as well, of the uncertainty of which treatment was best for whom.

Rick Bangs:

All right. Important questions, who funded and conducted the study?

Dr. Angela Smith:

So this study really did come from PCORI, the Patient-Centered Outcome Research Institute, which is a funding agency dedicated to in large part what they call comparative effectiveness research. What comparative effectiveness research is, there is evidence for two or more types of treatments, but what patients don’t have is which treatment is better than the other. I think that’s a really important distinction because we may know that there’s evidence for these various treatments, but when it comes down to it, a patient who is faced with these various treatment decisions needs to know which one is better for a certain subset of patients like them. So the PCORI really focuses on that. They also focus on being, what we term, patient-centered. So they have engagement awards. I mean, if you really look at the history of CISTO, it actually was born out of an engagement award where we partnered with the Bladder Cancer Advocacy Network to get the patient’s voice incorporated into the research we do. But then years later, it actually emanated into this larger CISTO study where we’re actually studying that particular topic.

Rick Bangs:

Okay. So with this study, you introduced several patient-centric aspects and I think the audience is going to find these interesting. For example, you chose not to do something that we would normally think about doing, which is randomizing people to one decision or the other, as to whether the patient got radical cystectomy or bladder preservation. So why did you do that? And was it controversial?

Dr. Angela Smith:

Yeah, that’s a really good question. I think that a lot of individuals in the research community think of randomized control trials as the “gold standard” in how we study certain diseases. I think there’s definitely reasons for that belief, and there’s also important other methods that should be considered for certain types of diseases. I think bladder cancer, especially recurrent non-muscle invasive bladder cancer is one of them.

As you mentioned in the introduction, I was one of the co-founders of the BCAN Patient Survey Network. That Patient Survey Network is really important because it essentially has the voice of patients in the BCAN and bladder cancer community at large. We asked patients various years to rank order like, what are the questions that are really unanswered? If you had more information evidence, you could make a better educated decision for the treatment you’re receiving. What came to the forefront was these questions surrounding what’s the best type of treatment for recurrent non-muscle invasive bladder cancer, and even more specifically, how do I choose between having my bladder removed versus sparing my bladder, and how long?

I say this because we actually went back to the BCAN Patient Survey Network to ask patients. Would they enroll in a randomized controlled trial? Remember, a randomized trial is, essentially, if you were a patient thinking about enrolling, the way that it would work is that there’d be more or less like an envelope. That envelope would be opened, and you would be randomized to either having the cystectomy or randomized to having a bladder sparing therapy. Probably, if you’re a patient listening to this, you might even, in your gut, think, “Wow, I don’t know if I would do that.” And guess what?

Rick Bangs:

Okay.

Dr. Angela Smith:

Yeah, over 95% of patients said, “No way.” There are certain types of diseases by which their patients really want a hand in that decision, and I call them patient preference, heavy decision-making treatment, this is one of them. But for this to be funded by PCORI, we really did have to show evidence why this “gold standard” method was not appropriate in a setting. So we did that, we showed them that, and I actually think that’s one of the reasons we didn’t get critiqued as to why we created that method. Because we showed through evidence that patients spoke, they’re like, “We won’t enroll.” And I will also add, there has been attempts at doing this, and those randomized clinical trials did not, I would say, fail in the sense that they did not meet accrual because again, patients didn’t want to enroll in such a study.

Rick Bangs:

Yeah. I mean, you’d have to be exactly on the fence.

Dr. Angela Smith:

Yeah, exactly. There’s just not many people who are, it’s very preference-driven.

Rick Bangs:

Right, right, right. People come in with a point of view. All right. So you did some other patient-centric things. What did you do?

Dr. Angela Smith:

Well, the other thing is thinking through what is the outcome. Anytime you design a study, you want to understand, “Okay, well, what is the population?” We already defined that. Those who had high-grade non-invasive bladder cancer, for whom. They had at least had BCG at some point in the recent past and then it recurred. Okay. So that’s the first one. But the second is really thinking about your outcome. What are you going to be studying? So again, we use the Patient Survey Network to understand and identify what are the outcomes that are important, and what is the most important one? What we discovered is that in this patient population, there was really a preponderance of individuals who felt that physical function was really important. I think talking to my own patients, that wasn’t necessarily a surprise based on the average age of patients who are… We know that that’s 74 years old in the bladder cancer population. That doesn’t mean that that doesn’t happen in younger patients and certainly older, but that’s the average. So physical functioning and just maintaining that quality of life was really important.

There were a lot of other secondary outcomes which were also very important, emotional well-being, things like anxiety, depression, finances. So we wanted to make sure we incorporated that. And then aspects that are related to the treatment itself, so urinary, sexual, bowel health, and survival, and then also some patient preference sort of decision-making elements. So we actually use that to design the outcomes, and of course… I shouldn’t say of course, because many patients don’t have this. We had an advocate advisory board, a group of patients who helped us to both design the study and then also make decisions as the study moved through accruing and move through the various stages.

Rick Bangs:

Yeah, that is not always done, and that’s I think an important aspect here.

Okay. So you’ve got these results, and you’ve kind of hinted at some of the domains that you researched. I think the results were surprising to some clinicians and perhaps some patients as well. So I want to start with radical cystectomy, which on several dimensions scored better. We know that bladder preservation scored better in some other dimensions. All right, for bladder preservation, where did bladder preservation score better?

Dr. Angela Smith:

Actually, what I didn’t mention are some of the more, I would say, obvious outcomes. Many studies look also at survival, like cancer-specific survival, meaning how many years you live that the cancer doesn’t recur. Also, progression-free survival, that means if it does recur, does it progress into a higher stage? And then overall survival, where you’re looking at just survival overall.

So I just wanted to mention that, and now I’ll answer your question, whether the outcomes in which patients who underwent bladder scaring therapy did better, so to speak, and there were a few of them. The first was bowel health and then the other was sexual health. I would say that wasn’t a surprise to me as a urologist because cystectomy, by virtue of the type of surgery where you’re actually operating on the bowel, you are actually quite literally cutting nerves that contributed to sexual health. That made sense to me, that it would be favoring the bladder sparing therapy arm.

The other 12-month outcome that was better was progression-free survival. Some of the questions that one might have is… This was only at one year so I think these survival outcomes, we probably need more time to allow the data to mature. But those were the three outcomes in which favored the bladder sparing therapy arm.

Rick Bangs:

Okay. So now let’s switch to radical cystectomy. Where did it do better?

Dr. Angela Smith:

So I think this is where the surprising… You mentioned there’s some perhaps surprising results, and I think this is where that occurred. Things like cognitive functioning, mental health, financial health, and also recurrence-free survival. Maybe that last one is not as surprising because you’re removing the bladder. So recurrence-free survival, you might consider, that actually does make sense because you’re actually literally removing the organ where it typically recurs.

But the other part I perhaps was a little more surprised, patients showed less anxiety, less depression, better financial health, and better cognitive functioning. The other little, I would say, subset is physical functioning. Now, overall physical functioning, and that was our primary outcome, there was no difference actually between bladder sparing and radical cystectomy. It was really important information in my opinion, because there was always this belief, and it was almost like an unspoken belief, but we didn’t have any evidence one way or another. That’s why this study was so important. There’s unspoken belief that, of course, you’re going to have this really major surgery, and of course your physical functioning is going to be worse. But this is where our studies are so important, because it actually wasn’t worse. It’s the same. And not only that, but what was favored in the cystectomy population are patients with like, for example, carcinoma in situ and some patients, some who were unpartnered, for example, because we looked at differing subsets of patients, physical functioning was actually better for those types of patients, patients with CIS or who are unpartnered in the cystectomy arm.

So I think those were surprising results, but I could posit a reason for some of those things, for example, for mental health, because we did some semi-structured interviews that are not yet published, but very recently were presented at the Society of Urologic Oncology and then at the American Urological Association annual meeting, that the patients actually felt a lot of relief when their bladder was removed, that translated to less anxiety, depression, which I think revolves around the uncertainty of cancer recurrence. So that’s my take on that, but that was the 12-month outcomes for the favored cystectomy.

Rick Bangs:

Okay, very logical. All right. Kind of pull this together, what is this in its entirety? What does this tell patients and clinicians?

Dr. Angela Smith:

I’ll start with misconceptions about what it doesn’t say and then I’ll end with what I think it does say. I think that there is a misconception that because some of these aspects were better in patients with cystectomy, there’s a misconception that cystectomy is better. That is not actually the results of this study, and I think that’s really important to distinguish. What it tells us is that cystectomy perhaps is not as “bad” as I think it has been believed to be in terms of the impact on physical functioning and emotional function, et cetera. I think what it does say is that either treatment, bladder sparing therapy and patients undergoing cystectomy, both have its role, and I think it opens the door for patients for whom perhaps cystectomy might be better to feel like they can go more confidently in that direction. And I think that’s a really important point.

The purpose of this study is such that we can start to identify, “Okay, you are a patient of this age. Your preferences are really X and Y. And therefore, for patients like you, cystectomy or bladder therapy seems to fare better.” It helps patients understand the variables that are more like them, of which patients like them did better. So that could be bladder sparing therapy depending on those variables, and it could be cystectomy depending on other variables, but it gives patients a little bit more understanding about how patients like them fared, and that is worth its weight in gold when a patient is facing these two very different treatment decisions.

Rick Bangs:

Okay. I do have one question which is, do you think over time the bladder preservation, because the treatments are changing, you might see different results on the bladder preservation side?

Dr. Angela Smith:

It’s a great question. I’m always a person who thinks with an open mind, so is it possible? Absolutely possible. Always think things are possible. I think we’re going to be seeing a lot of changes in this landscape over time. Right now, John Gore and myself in our research team has an NIH R01, which is a large study, evaluating some of these things, looking at, number one, long-term outcomes of these patients. So I think that’s one piece. Two, we’re enrolling some new patients so that we can include other patients receiving some of these newer therapies.

The second aim is looking at the molecular makeup, so to speak, of some of these tumors to see, are there some predictions based on their molecular composition that portend prognosis one way or another? So I think that’s going to be very helpful as an additional aspect of saying, “Okay, patients with this molecular makeup, these types of patients fare better in this type of treatment.” And then the third I think is really important, which is cost, because as you include these newer treatments, they tend to be more costly depending on insurance, and we wanted to study the impact of that specifically. So I think those types of questions which are actually currently being studied will help shed light on that question.

Rick Bangs:

Okay. Look forward to hearing more and then invite you back when you’ve got additional information.

So you’ve talked to some patients about the study. What have they told you about it?

Dr. Angela Smith:

So I think it’s been an interesting experience hearing the patient’s take on these results. I think that because it was a bit surprising on the cystectomy side, I saw a few different reactions. I think there’s always going to be an emotional reaction if the treatment has occurred in the past. I noticed various emotions, some disbelief and some surprise, but also affirmation, especially among patients who underwent cystectomy, as I mentioned, because there was this… I would call it a bias, honestly. I think there was a bias against cystectomy. I say that because, speaking to a lot of patients and providers, cystectomy is portrayed as this really challenging operation, lots of maybe, let’s call them, poorer outcomes, et cetera. I think this study questions that.

I think, yes, of course, there are aspects of cystectomy. I’m not making light of that procedure, but literally getting the data from patients themselves who went through this treatment, perhaps it’s not as biased toward the negative as it would lead us to believe. And I saw a lot of emotional reactions of patients who felt affirmed in their selection for cystectomy, and that I think really lifted my experience too. I didn’t realize that emotional experience was, I think, in the background.

So I think different patients receive these results in different ways, and that’s why I go back to the question you asked, which is, what does this study mean? And then what I added, what does it not mean? It does not mean that a treatment decision is wrong. It definitely doesn’t mean that. It just provides evidence to affirm either bladder sparing therapy for some patients and cystectomy for others, and that is really what the study provides. And I think that is this experience that I’ve noticed patients receive the results with.

Rick Bangs:

Yeah. To me, it indicates the nuances in these decisions and how important it is to have that shared decision-making discussion so that you’re on the same page and understand better what the implications of either choice are going to be.

Dr. Angela Smith:

That’s right. Yeah.

Rick Bangs:

Okay. You also talked to clinicians, so what do they tell you?

Dr. Angela Smith:

I would say it’s not as much of the emotional aspect of it. I think it is the surprise. It’s similarly the surprise about how well patients fared after cystectomy. I think that, and even as a clinician myself, it helps us counsel so much better. I think we were in a space where, and it is an uncomfortable space for clinicians, where we have to say, “Okay, these questions you have, which one’s better? Let me tell you my anecdotal experience talking to patients.” Anecdotal evidence is always uncomfortable because that’s all it is. It’s just like, “Okay, it’s my very small group of patients, this is what they’ve experienced.” By the way, it’s also probably biased by how I’ve received what the patients have told me or maybe have what they have not told me. So what these results have provided for clinicians, and that’s what has been told to me, also what I’ve experienced, is it just allows us to counsel with evidence. That makes us much more comfortable so that we’re not biased when we’re counseling patients. So I would say that has been the take here.

Rick Bangs:

Okay. All right. So what impact, if any, do you expect CISTO to have on standard of care? And do you expect guidelines to reflect any change?

Dr. Angela Smith:

Yeah. I think one of the ways that we set up CISTO through PCORI’s framework of engaging various stakeholders, patients being one of them, I already mentioned in our advocate advisory board. We also had an external advisory board, and that was hand selected such that we would have a voice to dissemination and implementation. So one of those members are individuals who are involved with, for example, the American Neurological Association guidelines and the National Comprehensive Cancer Network guidelines. And I do anticipate these guidelines to change because this is higher level evidence than we’ve ever had. I think that’s going to change very shortly. Guidelines take a moment because, of course, there are people who are on these committees, but I do expect that to change within the coming year.

Rick Bangs:

Okay. Well, full disclosure, I am on the NCCN panel, so we’ll look forward to hearing more on that.

Dr. Angela Smith:

Wonderful.

Rick Bangs:

All right. So you talked about R01. Any additional work beyond that that you anticipate as a result of this study or you might predict in the future?

Dr. Angela Smith:

Well, the other study that we haven’t begun working on, but we are in grant writing phases, is dissemination and implementation. I think that’s a perfect segue because you were asking about the guidelines, and yes, getting it in the guidelines, that’s one way to disseminate, implement, but we also know that guidelines alone don’t always translate to true implementation. So it’s just more of one of the elements that contribute to it. So we’re writing a grant right now with a letter of intent to PCORI on a dissemination implementation engagement award, and then hopefully that sets us up for success and a dissemination implementation award so that we can really think through how to do this in a meaningful way.

Rick Bangs:

Excellent. Excellent. Very exciting. Okay. Any final thoughts?

Dr. Angela Smith:

I think you hit all the questions, Rick. I’m really impressed. It was so easy to talk about this because it was a very natural flow. My final thoughts is really more of gratitude for the community. These types of studies don’t come together with just a few individuals that come together through a community. I think BCAN was that community, and BCAN is that community because it has such wonderful tentacles through all stakeholders who influence the bladder cancer experience. So I have a lot of gratitude for that partnership and all the different types of stakeholders who were really important for conducting such a large study such as this.

Rick Bangs:

Excellent. Dr. Smith, I want to thank you for sharing the highly impactful results of the CISTO trial, which compared radical cystectomy and bladder preservation, and helping us interpret your findings.

Dr. Angela Smith:

Well, I want to say thank you for featuring these studies. This is one more element of dissemination. So thanks for giving us the time to share this with the bladder cancer community.

Rick Bangs:

I am sure they’re going to be very interested. So if they do want to get more information, where can you point them?

Dr. Angela Smith:

So there’s a great PCORI website that PCORI is always dedicated to ensuring patients have all the upmost up-to-date information related to studies they fund. And this isn’t an exception. It is a long URL. So I have, what we call, a TinyURL, so I’m going to spell it out. This will take you to the full website that is updated over time, and that’s https://tinyurl.com/pcoricisto, P-C-O-R-I-C-I-S-T-O. And that will take you to all the different elements that went into the study, the design, the engagement, all of the papers emanating from this. So you can kind of bookmark it on your computer, because it gets added to you over time, and welcome anyone to look at it so they can get all that information for themselves.

Rick Bangs:

Okay, excellent. If you’d like more information on bladder cancer, please visit the BCAN website, www.bcan.org, or you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today. Please like, comment, and subscribe so we have your feedback. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Smith.

Dr. Angela Smith:

Thank you.

Voice over:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network or BCAN. BCAN works to increase public awareness about bladder cancer, advance bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.