Ashish Kamat: Hello everyone, and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, urologic oncologist in Houston, Texas, and it's a pleasure to welcome to the forum once again, one of my colleagues, Kelly Bree, who's actually also right here in Houston, Texas at MD Anderson, and I think sitting a few offices down from where I am right now. Welcome, Kelly.

Kelly Bree: Thank you so much for having me.

Ashish Kamat: Always a pleasure. So you were at the Think Tank recently, the weekend Think Tank, and one of the things that you have been very involved with, with the Think Tank, with IBCG, with many different avenues is measuring what matters, right? What's important for patients, patient-reported outcomes. So really interested to hear what you and your group are planning and what we're doing at the Think Tank, and then we'll chat a little bit at the end as well.

Kelly Bree: Perfect. Yeah, it was a real pleasure. I worked with Lindsay Harrell to plan one of the breakout sessions, really focused on how we can better incorporate the patient voice into our trials moving forward. And we had a wonderful panel: Dr. Angie Smith, Dr. Katie Marchetti. We had Casey Quinn, who works at PCORI, and we also had Robert Lippman, who's a patient advocate. And it was a really engaging session and wonderful to hear both the researchers' perspectives on how we can do better as physicians. It was great to have Casey there to hear what we can do to improve our applications for funding in this space. And then obviously most importantly, having Bob Lippman there to talk about his perspective as a long-time patient advocate who's been involved in many of the trials including the recent CISTO trial. I have a couple of slides I'm going to go through quickly just as a brief overview, talking about why incorporating the patient voice is important, when and how we should involve patients, and what questions should we really be asking.

And so it's critical that we incorporate patients to really improve the relevance and outcomes of the studies that we're doing. What's most important to you or me as urologic oncologists might not be what's most important to the patient that's sitting in front of us. So a 10% improvement in complete response rate for their high-risk non-muscle-invasive bladder cancer might be a big deal for us in a statistically significant outcome, but if it means that they need to come to the clinic more often, it doesn't really matter to the patients that we're treating. So having them involved to make sure the outcomes that we're looking at are really meaningful and important to them is crucial. It also helps us ensure that the study is feasible.

Angie talked about how having patients involved early was really critical for the CISTO study. It made them realize that they had to do a pragmatic trial where patients could decide whether they wanted bladder sparing or cystectomy, and that patients would never be willing to be randomized to a trial where we were deciding whether they were getting cystectomy or bladder sparing. It's really crucial, again, to have them involved early, and then it just ensures that we're really remaining patient-centered in our goals.

Again, when and how. Incorporating them as early as possible in the planning process is crucial to ensure that we're really selecting meaningful endpoints and outcomes for our trials. Also, by having patients involved, we can ensure that we're improving the recruitment, include them in the design strategy, ensuring that the study is feasible, as I mentioned. And they often have ideas about how we can improve inclusivity and ensure we're getting a diverse group of patients that are enrolling in our trials. The better the study design with their input, the more likely we are to have good recruitment and good patient retention, which obviously is critical to successful trials as well. They also can be instrumental in providing feedback on how we can better get outreach to those groups of patients that we may not be capturing in some of the trials that we've been doing thus far.

And then an important thing that we talked about in the session at BCAN is once we do these studies, how do we disseminate that information and how do we really make it patient-centered? And so having advocates involved helps ensure we can develop the results and deliver them in lay terms that patients can digest and really help inform their care moving forward.

And then finally, another thing that we discussed in the BCAN session is which questions should we really be asking and are we asking the correct questions? And this example that I have here is from a study for patients with kidney cancer, but what they found is that when they queried patients to see if the questions that we're asking using current PRO tools are really relevant to the questions that they care about, you can see here in the red, many of the questions that the current surveys ask about, they didn't feel were relevant to them. And so I think it's really important as we move forward with our patient-reported outcome work, that we really incorporate the patient voice and make sure that these questionnaires that we're giving to everyone are really capturing what's most important to our patients. And this just reiterates that, again, what domains should we really be addressing and are there areas of unmet need that our current questions and questionnaires are not addressing?

And so in summary, incorporating the patient voice really into all aspects of our clinical research design is critical. The earlier the better so that we're designing studies that answer the questions that our patients really care about and engaging them often throughout the entire process of our trial rollout and even as we disseminate the results is really critical. That's all.

Ashish Kamat: That's great. Thanks so much for summarizing that. It's almost like one of those things where you're like, "Okay, how come we haven't been doing this all along?" Because you and I, and many of the folks that we know and hang out with, we always consider the patient voice. But when you look at actually organized situations, trial designs as recently as 10 years ago, the patient voice was really never incorporated in the trial design. And that's why, like you said, you have statistical endpoints such as a 10% improvement in response rate at three months, which the patient really doesn't care about. What they care about is what's happening at 12 months, a year out, et cetera, et cetera, and all those things that you mentioned. But with that in mind, Kelly, how does your group plan to address the regulatory issues, right? Because obviously the regulatory issues such as the EMA or FDA, they have to follow certain guidelines and statistical considerations, and they can't really factor in these soft endpoints of patients not wanting to come to the clinic, et cetera, et cetera. What's the plan there?

Kelly Bree: That's a wonderful question, Ashish. And I think that it requires collaboration between both us as the providers and researchers and the patients to find some middle ground of something that is clinically meaningful but also patient-centered and meaningful. And I don't know if there's an easy answer. It's complicated, but I think especially for example, in the non-muscle-invasive space, as we continue to have more and more agents approved for patients with BCG-unresponsive disease and figuring out how we determine which of those are being prioritized and which we should be offering patients first, it really needs to be driven by what is most important to the patients, especially when the differences in response rates might be a couple of percentage points.

And that, as you alluded to, patients often want to know, "Does it mean that I can save my bladder a year from now, two years from now, not at three months, and does it mean that I can come quarterly or does it mean that I need to be coming for 20 visits per year?" And so delving deeper into some of those things that really matter to the patients, I think is going to be critical.

Ashish Kamat: Yeah, absolutely. And I didn't mean to put you on the spot there, but I thought maybe you'd already done some groundwork on that because last year at ASCO, I did lead one of these sessions on PROs, and then this year they had a follow-up as well. And one of the things that came out is that pharmaceutical companies and those that are sponsoring these studies really want to hear from patients, but they can't approach patients, so they rely on you and folks like yourself with the work that you're doing to sort of transfer the information from the patient in a curated fashion to them. So there's no conflict of interest or anything of that nature. So it's very important, I think, that we continue to work with regulatory bodies, with pharma, and get the patients to be heard in all different avenues.

One of the things that you are working on obviously is refining the PRO for the non-muscle-invasive part for the IBCG, and really looking forward to hearing from you. And we'll do this on a separate time, of course, what the next steps are when it comes to that. But from a more advanced stage of disease, say metastatic disease or muscle-invasive disease, have you, and is your group going to try to have different PROs for the different stages of disease, or is it sort of like, "Let's just hear what the patients have to say across the board?"

Kelly Bree: I think there are probably some PROs that'll be relevant to patients across the disease spectrum, but there are, I think, some nuances to what's important to patients at the various disease stages. And so ideally having a PRO where there are some basic questions for all the bladder cancer patients, I think is important. And then an opportunity for patients to answer different PROs if they have had a cystectomy and have a conduit or a neobladder versus patients who have undergone intravesical therapy and still have their bladder, I think is important for us to really be capturing the things that patients in each of those disease states really care most about.

Ashish Kamat: Right. And then the other thing that we always face is that this has become accepted in North America, but in many parts of the world, including in Europe, not just in Asia or Africa or elsewhere, but including in Europe, there's still not that much awareness that they need it or that this is beneficial to them. So it'd be great to see and hear what your group has planned as far as disseminating this information and this sort of paradigm change globally, because obviously we have to start local, but think global, right?

Kelly Bree: Yeah. I think partnering with groups like the IBCG that have a global footprint will be really critical for that. Ensuring these are translated into multiple different languages and can be easily utilized and accessed by people across the globe will be paramount as we work on developing these.

Ashish Kamat: So again, Kelly, I don't want to keep you too long, but what's the plan for the year? Because I think this working group is something important enough for a weekend that we're going to see this next year as well, right? So what does your group plan for the rest of the year? And can people who are interested and listen to this, can they reach out to somebody and ask to be part of the group?

Kelly Bree: Certainly. I mean, I'd love it if anyone who's interested could feel free to reach out to me. I think the next step, I'm working closely with Sarah Sutka and we're planning on presenting some of this work at the upcoming IBCG meeting later this week. And then the first step I think is really using the currently available PRO tools and getting a group of patients together to go through them and do something similar to what the kidney cancer folks have already done and tell us, "Are these questions really what matter to you?" And identifying the domains that are important and are already being appropriately addressed.

And probably more importantly, identifying the areas of unmet need and what type of questions do we need to develop to get at the questions that they really care about. I didn't include everything in this, they wrote about in this article about the kidney cancer patients, but for a lot of the patients it's like, "Do you feel happy? Is this treatment a burden to your family?" And none of our current tools are really addressing those questions. I think organizing focus groups and really diving into what the areas of unmet need are is going to be the first most important step as we begin to figure out how we can improve the PRO assessments we're currently doing.

Ashish Kamat: That's a great first step. And the World Bladder Cancer Patient Coalition did a similar worldwide survey of 400 patients and their caregivers in 45 countries. And there's a whole list of questions that were asked of patients, what's relevant, what's important. And then based on that survey, BCAN is doing something similar and more focused on North America. So we'll have the international survey that included North America but included 44 other countries. And then we'll have the BCAN study, and I think that will be a treasure trove of information for folks such as yourself and your team. Really looking forward to it. So thanks again.

Kelly Bree: No, thank you for having me.

Ashish Kamat: Absolutely.