Angela Smith: Thank you, Dr. Chang, and thank you for always being an advocate champion for the CISTO study. I really appreciate being here to share what we've learned. I'm going to share my screen here. At the SUO 2025, as you mentioned, Dr. Chang, we had the opportunity to have a panel discussion about turning PRO results into actionable data. Along with Dr. Chen from Kansas and Dr. Barocas from Vanderbilt, we gave a little bit of information about how we see that field. For myself and also Dr. Gore, who is my co-PI for the CISTO study, we wanted to talk about where we are in that study in turning PRO results into something actionable. I know that many people are familiar with the CISTO study, but for those who aren't, I wanted just to put in a quick slide to show the methods. This was a pragmatic trial in which patients with recurrent high-grade, non-muscle-invasive bladder cancer were basically enrolled in an observational fashion, choosing either bladder-sparing therapy or radical cystectomy as their next treatment choice. These outcomes were determined based upon patient input, also other stakeholder input, with the primary outcome being physical functioning.
This is something that is in press and has also been presented at AUA, but there were also a variety of secondary outcomes. You can see them on the screen, generic quality of life, emotional well-being, financial well-being, sexual, bowel health, urinary health, survival, and then most importantly for this particular presentation, patient preferences. Many people know the first aim was looking at all these outcomes, the primary outcome being physical functioning. There was no difference between bladder-sparing therapy and radical cystectomy. A lot of people don't realize we have a second aim to that study looking at the heterogeneity of patient preferences through time trade-off. That's what we really focused on in our presentation at the SUO. In terms of time trade-off and the way that we organized this study, we looked at both preferences and quality-of-life outcomes assessed at baseline, so that's pre-treatment, and then 12 months post-treatment using these time trade-off questions, where patients would indicate how many years of life they'd be willing to trade off in order to experience what they consider perfect health instead of their current health.
We wanted to look at treatment choice as a function of patient preferences for future health states, and we also wanted to look at health-related quality of life as a function of their patient preferences, because these two items are what would then allow us to better advise our patients who are coming and trying to make this really challenging treatment decision. I want to just give a snapshot of our preliminary results. This hasn't been published yet, but we hope to get that out there soon. This first is a scatter plot. The reason these are important is it shows you where these health state preferences exist and it also shows whether there are clusters, because in time trade-off, what we're looking for are certain clusters. What's really interesting here ... and I'll orient you a bit ... orange is those who underwent cystectomy, black is those who underwent bladder-sparing therapy. What you see here is that the scatter plot's all over the map. Sure, many people who preferred cystectomy also have a cystectomy. You can see there's more orange above the line, but there it is really scattered in terms of what they see the health states exist, and the same thing for bladder-sparing therapy. That's just something very interesting, meaning that this is a very patient-preference-driven decision, and it's all over the map in terms of their preferences.
The second digs in a little bit more in the radical cystectomy arm. These are patients who underwent radical cystectomy, okay? In this alluvial plot, what it shows is on the left, this is the baseline, what they determined as their health state utility for having a cystectomy before they even had it. On the right side, that's what they determined at 12 months. The wider the ribbon in each of these states, the more proportion of patients are in that particular category. What you really see is that in the 0.8, so those who underwent cystectomy who rated the health state of having a cystectomy as high, believed it was actually high at 12 months as well. That was the majority of those patients. Very few rated as high and then in the end thought it was much, much worse than it was, and you see that same pattern repeating. Those who rated a 0.6 to 0.75 health state utility for cystectomy, again, the majority, actually it was better than what they anticipated at 12 months. Same thing even for these lower-ranked categories. Even the lowest category, the higher percentages actually went up from what their expectation was, and I think that's really important to see and to share with our patients.
As I mentioned, the second thing we wanted to look at is quality of life change by preference. I'll orient you to this as well. This first, so if you look at the legend at the bottom, RC or BST, that first denote is what they actually got. These are patients, RC means that they actually got a cystectomy. The second one is what they actually preferred. For example, this dark orange is those who got a cystectomy and preferred to have it removed. This light orange is those who actually had bladder-sparing therapy but actually preferred a cystectomy. They preferred to have it removed. That gives us a little information about how quality of life change influences their preferences. I'll give you some examples here. What you see in physical functioning is those who actually had a cystectomy and preferred a cystectomy had a bit of a difference in physical functioning, but not necessarily as much as compared to somebody who actually had bladder-sparing therapy but actually preferred the cystectomy. Their physical functioning actually was worst among all. Then if you look at something like urinary function, for example, look at this, this dark orange line. These individuals actually had much better urinary function, and those are the patients who ended up having a cystectomy and preferred it. Perhaps it's because they had urinary issues to begin with, and it really improved their quality of life.
On the flip side, let's look at sexual function here. The individuals who had the worst sexual functioning change, these were individuals with this dark gray. They had a cystectomy, but they actually preferred to retain their bladder, perhaps because they had really good sexual function to begin with and so they were hardest hit by having that procedure. I think this is really helpful in the end, because what we're trying to turn into next steps is utilizing some of this time trade-off data to develop some conceptual grouping of patients with identifiable traits. As an easy example, older men who are experiencing poor urinary function and no concern about erectile functioning, who favored cystectomy or even are neutral with cystectomy, they probably should proceed with cystectomy, because it looks like from a preference perspective, from a quality of life perspective, all of those things are favorable in that category. There's probably some other conceptual groupings of patients that will help us when we're in those really challenging conversations with our patients to help them choose the treatment that's best for themselves, but we still need to await some long-term clinical outcome data to create those groupings. In the end, what we really want is a simple visual tool that represents what we consider a patient like myself, and that's why it's going to be important to continue our patient advocate input with our advocate advisory board. It's not the same as a nomogram or some discrete choices instrument, but something really straightforward, something really practical that we can use in that moment for clinical use, and is more of a checklist of patient attributes, so that's really where we are.
Of course, I just want to acknowledge, I mean, it really takes a village to put something like this together. Our CISTO Collaborative, all the study participants, BCAN, the Bladder Cancer Advocacy Network, PCORI for funding, all of that is necessary to put together such a large pragmatic trial. Again, thank you, Dr. Chang, for giving me the opportunity to present this today.
Sam Chang: Dr. Smith, what a presentation. Just a lot to try to actually conceptualize, which I think is the key point here, because you all want to conceptualize a version of education for the patient that is easy to understand and easy to process. Your last slide I think was really to me the most telling, and I think for the entire audience during the SUO, is yes, we have a lot of nomograms, we have a lot of algorithms, we have a lot. At the end of the day, for a patient, the fact that your score is 0.82 on a nomogram or algorithm, it's very hard to compute. Do you have any idea of how you all are going to conceptualize, obviously with the patient advocates being very important? How are you going to conceptualize or have an idea of how are you going to group that and show that to a patient? Is it going to be a drawing? Tell me some ideas that you guys are thinking about to help patients make that decision.
Angela Smith: Yeah, we're still coming up with that, so I encourage anyone listening to this to provide their ideas. I think that there's a few front runners, and even patients in our advocate advisory board have suggested this. I think one is a visual tool of those groupings, just even maybe a one-pager, and creating just a few attributes that are really telling that create the cluster, so maybe it's age. It might be sexual function. That's actually a big one, because that helps decide. Urinary function is another really big one.
Sam Chang: Yes, yes.
Angela Smith: I know. I know, Dr. Chang, you see patients with bladder cancer, and that can be a really big driver of that preference-sensitive decision-making. I think that's the key. What are the most preference-driving attributes, and saying we're not going to capture them all, but we're going to capture the big-ticket items, and then actually having some visuals. You're a person who urinary function's a challenge for you, or it's going really well but sexual function is really important. Having these conceptual groupings in the most preference-sensitive areas, attributes, I think is one area. I could also see a very straightforward checklist, and it spits out like that. There's one wave where you just look at the visual and you just start to compute on your own. That might be helpful, but another ... and some patients do want that. They're like, "Just give me the answer," not to say that it would be an answer. We would probably couch it in terms that, "Many individuals with the selections that you chose choose this, and here's why, understanding that it might not still be a right answer for you," but it gives them a place to begin. Those are the two things we're toying around with right now, but always open to interesting, innovative, other ideas.
Sam Chang: Yeah. No, really good point. I know Chris Saigal at UCLA and his co-collaborators are really using a similar type of checklist for patients in terms of prostate cancer, and taking the next steps to trying to decide to make that decision. I think it also hearkens back to what you said, of people who are symptomatic in a certain way can really gain benefit from one treatment vis-a-vis another. That, I nodded my head with the urinary symptoms. If you're having a lot of problems with your bladder, the idea of giving another treatment to the bladder, it makes some sense. That's the organ of issue and problem. We have a built-in bias, and I did as well, of like, okay, we should do everything we can to save your bladder. Having that idea of the baseline characteristics, it was very telling. I don't even know what you'd call that.
Angela Smith: The alluvial plot.
Sam Chang: Yes. Yes, exactly. It's very telling when you had that the people who scored very highly, 0.8 and above, the vast majority that really maintained that after bladder removal, et cetera. I thought that was one of the most telling graphics, and I think people in the audience definitely thought that as well. Dr. Smith, you have this group. You come together and you conceptualize different ways then to help patient education. What's the next step then after that? I know you all are doing some long-term follow-up. Tell me, where is CISTO going next?
Angela Smith: Yeah, great question. Yeah, so we are. We're doing long-term follow-up of the individuals who are already enrolled in CISTO and really representative of the data that I just shared, but we're also enrolling new patients too. Our idea is to have also tissue data, to look at things in a variety of ways. That's what BEST CARE, we're calling it BEST CARE, also known affectionately as CISTO-II, is all about, because we also know, from a provider perspective, it'd be really nice to have some of this data or some of this tissue and biomarker data, to predict who's going to recur quickly and who's not. I think that will eventually add into these conceptual groupings. Maybe some of it's patient-preference-driven, and some of it is going to be understanding what the predictive ability of, for example, biomarkers are going to do. We're partnering with Valar Labs to try to do that in a meaningful way, and it's really exciting. I think it's bringing in all of these elements to a really complex decision-making algorithm, but again, multi-stakeholder input, because we need the biomarker data, we need the patient input, then of course we need provider information too, of how we're putting it all together.
Sam Chang: No, I think that that combination, I mean, to me, this would be quite unique. Obviously we have clinical trials, we've tried to incorporate quality of life, patient portability, but this emphasis on understanding from the stakeholders and the fact that you all obviously included the patient efficacy as a vital part of not only developing the trials, but then following up and where do we go next, but now you tie in the molecular data, the actual histologic data, biomarker data, et cetera. Very, very exciting, because you can see where, if patients knew that their chance of recurrence is quite high, that would really impact their psychological choice of, "Oh, if I'd known, et cetera, et cetera, I would've done."
Angela Smith: Right.
Sam Chang: Very, very exciting. I mean, you have been such a leader, obviously at your institution, president-elect of the Society of Women in Urology, your Young Investigator Award from the SUO. I don't think the accolades really give you enough credit for everything that you've achieved. We are all indebted to you very, very much. Dr. Smith, look forward to seeing you again, look forward to seeing you personally, and obviously look forward to the next findings we have with CISTO and all the other research that you're involved in.
Angela Smith: Well, thank you, Dr. Chang. It's been a pleasure being able to share all of this with the world.