The "Get Moving Trial" Home-based Pre and Rehabilitation Intervention for Muscle-invasive Bladder Cancer, BCAN Translational Clinical Trial Award - Sarah Psutka
March 29, 2023
Sarah Psutka, MD, MS, Urologic Oncologist, Associate Professor of Urology, Department of Urology, University of Washington, Seattle, WA
Ashish Kamat, MD, MBBS, Professor, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, President, International Bladder Cancer Group (IBCG), Houston, Texas
Ashish Kamat: Hello and welcome again to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urologic Oncology and Cancer Research at MD Anderson Cancer Center. We have again today with us on the platform someone who's well known to all of you, Dr. Sarah Psutka. We have Professor Psutka on this platform multiple times to talk about our studies and her papers and things like that. But today, it gives me an immense pleasure to actually welcome you, Sarah, and congratulate you on this really impactful award that you got from BCAN on the Clinical Translational Trial Award. Most of you know what this award is. But for those that don't, this is a very impactful, very important award that BCAN has selected someone like Dr. Psutka to give to, and this has a real impact on patients, so the potential to have a real impact on patients. With that, Sarah, I want to congratulate you and hand the stage over to you.
Sarah Psutka: Well, thank you so much, Ashish. This has been an incredible week, and I am really excited to share with you the plans that we have for this trial that BCAN has incredibly generously funded. We're calling this the Get Moving Trial. It's a phase I/II trial of a home-based pre and rehabilitation intervention with an app that I'm going to just tell you about called ExerciseRx in muscle-invasive bladder cancer.
We've talked about this before, you and I actually, about we've all thought about how we can improve outcomes for patients with bladder cancer. We've spent a tremendous amount of time over the last two decades improving our surgical technique, implementing ERAS pathways. We've spent a lot of time defining survivorship pathways and developing ways that we can help our patients rehab after treatment.
I've spent most of the last 10 years thinking about risk stratification and how we can use quantitative methods to risk stratify our patients to help them choose the right treatment.
Where that's all gone, the natural extension of that, has been to think about this concept of prehab, which is a just burgeoning research field. Prehabilitation describes the process of improving a patient's functional capability before a surgical procedure or any kind of treatment with the goal that we improve the patient's ability to withstand post-operative inactivity, and then the treatment-associated functional decline, just the stressor of surgery.
This is just a quick PubMed search. You can see this is an area that has really, really burgeoned over these last couple of years, specifically with just an incredible amount of interest, and especially in the surgical field. There's a lot of prehab programs out there, but one thing they all have in common is these three domain focus. The core domains of prehab include physical activity, nutritional supplementation, and then mental or cognitive interventions. Really, what we're looking at here is trying to find those personalized modifiable risk factors that each patient might have that we can target with specific interventions with the goal of not only improving candidacy for treatment, but then also, of course, improving treatment outcomes.
The problem is, if we look at the prehab studies that are out there in GU oncology right now, many of them have not achieved the goals that they hoped they would. With exercise and nutritional interventions in genitourinary oncology, we've not seen the needle move with respect to surgical complications, length of stay, mortality. There have been a couple of studies that have demonstrated the feasibility of doing these fairly intensive, especially exercise interventions.
One study I always highlight is the really great study that Deborah Kay led out of Michigan, where basically it was a 90-minute exercise intervention given three times a week. But they demonstrated that it's possible to do, it's feasible, and they did improve quality of life in patients, and especially the mental component actually improved sustainably. There weren't any adverse events. But in terms of the real core targets, we don't seem to be moving the needle.
Then the other big issue is that there are some problems in terms of how the exercise interventions have been designed. If we look at this concept of therapeutic validity, which really looks at whether or not the exercise intervention is something that is widely generalizable and really targeted at the problems that we're trying to solve. So here, if we're trying to help patients who are undergoing abdominal surgery get out of bed sooner, get up and moving faster, get back on their feet, get back to living independently, get out of the hospital sooner, and make it through the surgical period with lower risks of complications, we're missing the mark. One of the issues is a lot of the exercise interventions that have been selected and tested are things like high-intensity interval training. Well, as much fun as that kind of intervention may be if you are someone who is an elite athlete, the vast majority of our patients who are undergoing surgery for urologic malignancies, those are not even feasible. A 30-minute high-intensity anaerobic threshold workout is just not something that someone who requires an assistive device to ambulate is going to be able to undertake. So one of the biggest issues is, of course, they're not even really generalizable to our patient population.
I had the honor at the Bladder Cancer Advocacy Network Think Tank in 2022 of leading the prehab session with my partner in crime at the University of Washington, Dr. Hanna Hunter, who's a physical medicine rehabilitation specialist with fellowship training in cancer rehab. Our patients made it loud and clear that there is a real need. They vocalized this need for widely-available prehabilitation that really anybody can undertake. There was a lot of buzz about our session. I think it was a really great conversation with the patients, but this need became very clear, and the barriers to prehab became especially clear as we talked to our patients. They not only talked about the importance of having a prehab intervention that is resource non-intensive, so something that in the setting of patients undergoing chemotherapy, like for example, neoadjuvant chemotherapy or undergoing preparation for surgery, wasn't going to drain their emotional and social resources. They weren't going to have to get to a gym multiple times a week. It needs to be home-based to be sustainable.
The question came up, especially for patients who live far from the centers where they're being treated, "Can we leverage telehealth or some sort of remote access technology to help make prehab more available?" There's certainly issues with respect to scalability and getting across urban ... Especially many of our patients at the University of Washington, we treat this kind of whammy region. We have patients coming from five states, sometimes flying eight hours to get to see us. We need to be able to have patients have prehab available to them even if they live far from our urban centers.
Then there's also an issue with making sure that patients are doing it safely, but not impinging on patients' privacy. So we need to be able to have this be something that's widely appropriate and comfortable for patients to accept.
In terms of pragmatism, it needs to be adoptable across everyone with bladder cancer. It needs to be something that anybody, even with an ECOG performance status of three could undertake, not just the ECOG zeros. We really need to personalize these programs because everybody has specific, whether it's balance issues or strength issues. Then, of course, financial toxicity is key. We can't be adding further cost to patients by asking them to undertake a prehab program that, for example, is going to drain the bank with gas prices, getting to the gym, or getting to the hospital, taking them out of work even further.
These were all of these problems that were really well vocalized by our patient population.
In the setting of that, Hanna routinely provides these very personalized, pragmatic exercise interventions to our patients. She and I sat down and started thinking about how could we actually use exercise as medicine in a sustainable, pragmatic way that is widely adaptable and meets this vocalized need that came directly from our patients at the think tank?
Well, one of the wonderful things about working at a university, like the University of Washington, is we have this incredibly deep bench of researchers who are in other fields that sometimes we have the opportunity to collaborate with. Hanna reintroduced me to someone who I actually went to medical school with, Dr. Cindy Lin, who's in our Department of Sports Medicine. Cindy is an amazing researcher who has partnered with the Engineering Department over the past couple of years to develop a program called ExerciseRx. This is a cellphone-based app that has been geared towards patient utilization that she uses primarily in her sports medicine population, so a population recovering from trauma surgery, orthopedic surgery, amputations. This app is integrated in the electronic health record, and it utilizes the cellphone's capability as a ... So any of our iOS devices, it allows us to use the sonar capability and the step tracking count to assess a patient's participation in the exercise interventions that are being recommended. We can use the activity trackers that patients already have in their iOS devices to sense their participation in exercise interventions.
We got together. We looked at how we could use this ExerciseRx app. You can see this is what the patient sees on their cellphone tracking their activity daily in their personal records. We can set reminders to help patients utilize these apps. This is how it interacts with our Epic electronic health records. So this is on the physician side, what we see. We can see how patients are doing. Are they meeting their goals? If they are, we can send them little words of encouragement. If they're not quite meeting their goals, we can ping them and say, "Hey, you're doing great, but we hope you can maybe try to do a little bit more activity today." We can really support them as we're encouraging them to integrate this exercise into their daily life.
Then we designed this trial. So the Get Moving Trial is going to have two phases. The first phase is really going to be to take this app that is currently being utilized in our trauma population and refine it for patients with muscle-invasive bladder cancer who are anticipating undergoing a treatment with neoadjuvant chemotherapy and radical cystectomy. Then we're going to use our engineering team to refine this app and really make it personalized for our muscle-invasive bladder cancer patient population.
In Aim 2, we're going to run a phase I/II clinical trial, and we're going to look specifically at whether utilizing a personalized, home-based prehabilitation intervention starting before chemotherapy is initiated and throughout the time that patients are undergoing neoadjuvant chemotherapy and then in the three months after radical cystectomy. We're going to see how we can move the needle on a patient's physical function, and we're going to specifically use the outcome of the short performance physical battery, which is essentially a balance and lower extremity strength and gait speed assessment that has been validated and is recommended by the National Institute on Aging.
Then we're going to look at a number of implementation measures. Then specifically from the patient side, we're going to look at patient-reported quality of life. I have an interest in body composition, so we'll look at muscle mass measures. We'll look at assessments of frailty. Then we're also going to see how this impacts clinical outcomes with respect to chemotherapy-associated adverse events and surgical outcomes.
The intervention is actually going to be a personalized intervention designed by Dr. Hunter and her team. This will be the one intensive assessment that the patients will all go through, where she'll do a complete physical assessment and understand that patient's individual physical risk profile. Then we'll recommend a 20 to 30-minute per episode intervention, mostly focusing on core strength and essentially walking that'll be ... we'll recommend patients to undertake four times a week. This will all be administered through the app, and we'll be able to assess adherence by both a Fitbit monitoring, as well as the use of the sonar capabilities on the app.
This is the conceptual model for the trial. Our inclusion criteria is broad. We really designed this trial to be highly generalizable to any patient undergoing neoadjuvant chemotherapy and radical cystectomy. Patients will be randomized. We anticipate enrolling 102 patients, and then we'll track patients as they go through their ... starting at the pre neoadjuvant chemotherapy CT scan. They'll undertake the intervention through neoadjuvant chemotherapy. We'll repeat the imaging. This will be another muscle mass assessment right before surgery. They'll go through the surgery. Then the final followup is 90 days after surgery. The primary outcome, as I said, is the SPPB with other endpoints that we're looking at, physical activity rates, adherence, usability, and health-related quality of life, as well as clinical outcomes.
I think this just brings me to something that I've been thinking about a lot over the last couple of years, which is we talk a lot about patients' vulnerabilities and risk profiles. That's really what I've spent the last 10 years trying to study. But I think I'm reframing this in my mind because really the converse of vulnerability is resilience, which is the ability of a patient to maintain their psychological and physical functioning in the face of stressors. Cancer is, I would say, one of the ultimate stressors, as are all the treatments we ask patients to undergo. How can we actually help our patients become more resilient as they're going through cancer treatment? The question here is whether or not prehab can meet that target.
The potential of prehab will vary based on every patient's individual risk profile, but I do think that the prehab is the answer to that patient's question when they're sitting across me, and they say, "Well, what can I do to make things better? How can I improve my chance of getting through this more safely and more effectively and more successfully?"
We can hopefully find that we can use this personalized intervention that is going to be scalable and pragmatic. It's much lower FI than what a lot of people have tried to do before, but hopefully it's going to be something that's actually sustainable and can really be integrated into patients' daily lives to optimize patients for surgery and maybe even improve candidacy for treatment. That'll be something we'll test in the future.
We're definitely working here to reassign the locus of control. I know cancer strips that from all patients, but by putting some degree of that control back in the patient's hands, we're hoping to help empower patients and engage them, and then hopefully build resiliency.
This would be completely impossible without our amazing research team, Dr. Hunter, Dr. Lin, and then one of my longterm research collaborator, Dr. Florian Fintelmann at MGH, who does our body composition assessments with an artificial intelligence-based algorithm that essentially segments CT scans. My partners in urologic oncology, Doctors Gore, Wright, and Lin in our bladder cancer working group. Of course,
I am just so incredibly grateful to BCAN. They have supported me from the beginning of my career with respect to the research that I've done and also in helping me provide better care to my patients. We are all so excited to undertake this project and really hope that we can make some serious advances in prehab science that will ultimately help us reach patients more widely. So we say, it's time to get moving.
Ashish Kamat: Thanks so much, Sarah, for sharing that with us. Again, congratulations on this award. As you mentioned, I've been part of BCAN since its inception, and just as you mentioned, it's been great to see the support that BCAN has been giving to young investigators like you used to be. Well, you're still young, but when you first started the new career and to see you blossom into what you have now and get this award is truly heartwarming. It's great for our patients too because the way BCAN supports us helps us support our patients, which is why we're all in this together.
Let me ask you a couple of general questions, not to delve into your research too much because that was very self-explanatory. But what would this award and the work that comes out of it mean to our patients? In just lay terms, what do you think our patients can take from this once you show what I think you will show?
Sarah Psutka: There's a couple of things. I would say that the patients vocalized a need. They want to have something positive to focus on that will help them get through therapy more successfully. If we can demonstrate that we can create a pragmatic, widely-scalable prehab program that anybody can use regardless of their financial ... Because here's the thing. In the United States at this point, market research shows that well over 85% of individuals, and even older individuals, have iOS-based smartphones. So this is something that could be widely used. This could be scaled easily. We're talking about exercise interventions that do not require a gym membership, do not require specific activity or equipment at home, and aren't going to take patients out of the home or take them away from their jobs or take them away from their families. So if we can create a pragmatic and scalable exercise intervention that's personalized, then we can start to get this to people across the country.
At the think tank, patients were saying, "Why didn't anybody ever talk to us about this?" Well, at that point, prehab was thought to be something that had to be done in a gym. For the most part, even over those past couple of years, if you look at the vast majority of prehab studies that are out there, they're supervised, intensive exercise interventions that for the most part only really young, healthy people can undertake. So if somebody is mostly using a wheelchair and mostly confined to their home, that's just not going to be feasible. But there are core exercises that can be done safely lying on the floor at home that can improve abdominal strength, the ability to take deep breaths, and ultimately can potentially impact ability to help with transfers and getting out of bed after surgery, which is really one of the things that we need to help patients with.
We're hoping that this is something that's really going to bring prehab to patients more widely and make it easier for physicians to recommend as well. The truth is, our clinical practices are so busy, trying to do exercise training on top of all that we have to do in terms of talking to patients about the oncologic treatments we have available, what this all means, what the expectations are from a survival standpoint, and side effects of treatment and the complications of surgery, we can't undertake this, the exercise training, on top of that in an oncology practice. But we can partner with our specialists, our expert researchers in prehab and sports medicine. We can leverage their incredible knowledge base and understanding of how physical activity can improve medical outcomes, and we can make it generalizable.
I've been trying to think about how do we take something that is really aspirational and make it easy and pragmatic? I think that by leveraging the tech that Dr. Lin and her research team have been working with, I think that this is something that we could actually make pretty widely available.
Ashish Kamat: Yeah, and I think so too, because again, I've been talking to patients about prehab in some form or the other for the last 20-plus years. But when they ask you, "Well, how do I do it?" that's when we end up giving them general advice. "Go to the gym, walk more, climb stairs," et cetera. But having something like this that is structured would clearly be very, very useful both to our patients and their carers at home.
Sarah, in closing, because I know a lot of people, including me, look up to you, so piece of advice to folks that are coming into the bladder cancer field that are looking to do similar research. What advice would you give folks that are getting interested in this line of work or in bladder cancer prehab in general? What advice would you give people that are looking to maybe emulate you and apply for a similar award to BCAN?
Sarah Psutka: That's incredibly kind of you, Ashish, because I look up to you. You've been somebody who's inspired my career.
I guess I would say two things. One, listen to the patient. The patient will tell you what they need. This trial came from Hanna, and I really ... I think having the opportunity that the patients very generously sharing with us at the think tank what they needed. I've seen the benefit of prehab in my patients who I've sent over to Hanna. She's had them doing core exercises and just improving hip girdle strength. I see the benefits when it comes to after radical cystectomy. I see them getting up and walking more easily.
I think it's that concept. I think a lot about somebody who always inspired me when I was training was Judah Folkman, who many of you, I'm sure, know, the father of the discovery of angiogenesis. I had the opportunity to work in his lab when I was a medical student and remember just listening to him talk about the fact that you just needed to keep your eyes and ears open because the problems find you if you actually look for them. This is a problem. The problem is patients don't know how to ... We don't have the ability to give patients something like prehab that works, that's acceptable to them. So they've helped us to find the barriers, and now it's up to us to find the solutions.
The other thing though is make friends and build bridges because nothing that I have done would be possible if it wouldn't be for all the people that I work with. I think of myself as a hub or a node that brings people who have all this incredible expertise together, and we think about how to apply it in innovative ways. I have an awesome team that I'm a part of, and I'm just a part of that. But we all work together. It's a bunch of really, really motivated people who put our heads down and work hard every day to try to solve these problems. It's been fun to reach far afield into sports med and cancer prehab, or with my partner, who's an amazing radiologist at MGH, who has this AI capability who took what I was doing all manually for the body comp stuff. He's been able to automate it. So we've worked together for years now trying to figure out how we can scale that up.
So I think listen to patients and build teams have been the two things that have really helped me. Find people like you and the people at BCAN, the people at the think tank who have been amazing inspirations that I just keep looking up to. We all go a lot further when we work together. So I'm just really grateful to have the chance to take what has been a long-term dream to run a prehab trial. We're going to make it a reality. I can't believe that that's the case, and I'm super excited for what that's going to look like.
Ashish Kamat: Great. Great advice, Sarah, as usual, I want to congratulate you once again on this award. I do want to thank BCAN for selecting you for this award, but also for all the work that they do for us and our patients and allow us to reach out to our patients. It's truly phenomenal to see what the organization has done.
Lastly, I want to thank UroToday for giving us really this platform to showcase you on this award and everything that's going to come out of it. So thank you again, Sarah, and congratulations.
Sarah Psutka: Thank you so much.