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Zach Klaassen: Hello, and thank you for joining us for this UroToday discussion. We're at the AUA 2023 in Chicago. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia, with me, Sarah Psutka, who is an associate professor at the University of Washington, Fred Hutchinson Cancer Center in Seattle. Dr. Psutka, we've had many conversations about this stuff in the past. We're excited to talk again about muscle-invasive bladder cancer and really walking the listeners through risk stratification, some of the work you're doing with your grants.

Sarah Psutka: Thanks so much for the opportunity to talk about this, Zach. As you know, this is something that we've been talking about for a long time, and I think it's just such a critical topic in this patient population. I'm really excited to be here.

Zach Klaassen: It's great to have you. So I think we both take out bladders, we both do cystectomies. And if you can walk us through, why are those patients so at risk? These are the patients where they stay in the hospital usually the longest. They come in with their disease... What makes them the high risk patients that we operate on?

Sarah Psutka: I think there's two things. Well, probably three. The first is the surgery itself. This operation is not just a "routine" oncologic procedure where you're taking a tumor out. There's a big reconstructive component of it. And it's not just a GU surgery. It's also a bowel operation. So you're talking about a major operation that takes several hours to many hours. Average length of time is somewhere in the three to potentially seven-hour range, depending on the case and the complexity of the patient's anatomy. But then the other part of it is the patient. And so, we know that patients with bladder cancer overwhelmingly have a considerable number more comorbidities than the vast majority of our other patients. So they, on average, have about eight comorbidities. That's the research room Tullika Garg from a long time ago. It's a great paper in JU.

Zach Klaassen: Still holds today, doesn't it?

Sarah Psutka: Right. I still use it on every single topic. But in addition, patients with high burden of comorbidity, but they also have a high burden of something called frailty, which is really a concept multi-domain assessment of vulnerability or risk. And these patients are the most at risk for basically not being able to bounce back. Their reserves are lower, and so you're subjecting them to a major stressor.

Zach Klaassen: That's right.

Sarah Psutka: And they're starting from a lower point where they just don't have the resiliency to get back, and it's multifactorial. It's physiologic. It's sociological. It comes in all different areas. So it's an intrinsically challenging situation, high-risk surgery, high-risk patients. And then, you take in the fact that it's a high-risk cancer. And many of these patients, not only are they high risk to begin with, but they're coming in after we put them through four months of cisplatin based chemotherapy.

Zach Klaassen: Absolutely. It's a great point. These patients really do come in de-conditioned. The one thing I've noticed in my practice in Georgia, especially the last couple years, is the importance of the social structure and whose going to help these patients when they go home?

Sarah Psutka: Yeah.

Zach Klaassen: Can you talk a little bit about that, how you evaluate that?

Sarah Psutka: Absolutely. I know we wanted to talk a little bit about this whole concept of the comprehensive geriatric assessment.

Zach Klaassen: Absolutely.

Sarah Psutka: And so, CGAs, or comprehensive geriatric assessments, are guideline recommended by international guideline bodies at this point as a first point of assessment when you're looking at patients who are older or medically complex, who you need to take through a challenging cancer operation in order to determine what's the right treatment for them. And one thing I've really tried to step away from in my practice over these last couple of years is this concept of the eyeballing a patient and getting a gestalt impression of fitness for treatment. We really can't do that in 2023.

Zach Klaassen: We all do it-

Sarah Psutka: We all do.

Zach Klaassen: But we have better ways to do it now.

Sarah Psutka: There are better ways to do it, and there are better ways to use the data, use objective risk stratification measures that are out there. One of those is a CGA. And so, what is a CGA? A CGA is a multi-domain assessment that looks at specific... I call it a risk and resilience profile or a vulnerability profile. The idea is, you actually find the risks that then you can act on and maybe move the needle on. But one of those risks is exactly what you're talking about. It's the social structure. It's the social support. Who's going to be at home? Who's going to help those patients as they recover? Who's going to help make sure there's food in the house? Who's going to make sure that they get to their doctor's appointments? Because truthfully, the operation is tremendously deconditioning as well.

Zach Klaassen: Yes.

Sarah Psutka: And so, a lot of these patients... 25% of them, historically, went to rehab facilities or SNFs. And now, we really need to think about how do we try to avoid that? Obviously, because-

Zach Klaassen: They don't want to go.

Sarah Psutka: They don't want to home. They want to go back to their own house. But how do you make sure that they're well-supported at home?

Zach Klaassen: Right. So talk a little more about your work with the CGA and some of the grants that you had. I know you've had some really great success over the last few months, getting some really important grants.

Sarah Psutka: Thanks.

Zach Klaassen: Because the operation hasn't changed. We know that in terms of outcomes, robotic, and open is about the same. It's the patient probably, rather than the approach. But your work is important because it's going to help us, A, select patients, and B, try to improve on getting them through the operation, home, rather than a rehab facility. So if you can just expand on some of that.

Sarah Psutka: Thank you. It's been an exciting year because a lot of the things that we've been working on are starting to come to fruition, which we're really thrilled for. So I think the story for me started actually thinking a little bit about this concept of just body composition and obesity. Which obviously, when I was starting my fellowship, the concept of whether or not obesity was a risk factor for surgical patients was really being dived into robustly. But the problem was, the signals were all over the map because BMI can either be... In some studies it was protective, in some studies it was a major risk factor for bad outcomes. So that's when I got into understanding, deep diving body composition and thinking about things like muscle mass, and adiposity, and how those are different competing risks.

But taking that one step further, you've got then form. And the question is, what about function? And that's the frailty piece. That's the physical function. It's the cognitive function. And then that leads directly into these multi-domain assessments or comprehensive geriatric assessments. I think the way I break it down is, we have really good tools if we look at the cells under the microscope. If we know histology stage and grade, we can do a pretty good job of telling a patient what their risks are for that cancer coming back and the likelihood that they're going to be alive in sometime period, or that they might be at risk for death from their disease. We also have really good tools to predict complications. The NSQIP ACS risk calculator-

Zach Klaassen: It's excellent.

Sarah Psutka: I think is a really helpful tool to use when you're counseling patients about short-term outcomes. What we don't have is really good tools to tell patients, what's the likelihood they're going to get home, they're going to be in their home a year later, they're going to be in home and be independent, they're going to be in their home and be able to make their own food, or get back to work, or be taking care of their grandkids? All the things that matter.

Zach Klaassen: And these are the questions they ask us in the clinic, right?

Sarah Psutka: Right.

Zach Klaassen: They don't know about the surgery.

Sarah Psutka: Exactly.

Zach Klaassen: They want to know, when can I go back to work? When can I go to the beach? Et cetera.

Sarah Psutka: Yeah, exactly. And truthfully, we just don't have tools that can predict those things right now. There are a couple of studies that have shown a little bit about what happens to functional outcomes after treatment. And Angie Smith had a really nice paper in JU a couple years ago that showed the physical function decline. I think that what we've been focused on understanding is, let's really get into understanding what happens to a patient's function and independence. And then, let's start to understand how we can change that. So to get to your point exactly... So right now, we have funding from the National Institute on Aging-

Zach Klaassen: Great.

Sarah Psutka: To, over the next two years, prospectively basically run... It's almost an epidemiologic study.

Zach Klaassen: That's great.

Sarah Psutka: We're looking at what happens to patients' function, so their ability to complete their ADLs, their activities of daily living, and their instrumental activities of daily living, as they go through neoadjuvant chemotherapy, and then as they go through the recovery after surgery. So it's two hits. There are two stressors here, not just one.

Zach Klaassen: Absolutely agree, yeah.

Sarah Psutka: I know from research that I did when I was at Northwestern and then that we've done subsequently at University of Washington, I know that muscle mass is going to decline by about 6% in this patient population, in folks getting chemo. But we don't really know what's going to happen to their physical function, their ability to live their lives. So we're going to gather that data.

Zach Klaassen: Excellent.

Sarah Psutka: And then the other thing we're going to try to figure out is, if we can understand and describe what happens, can we start predicting who's at the greatest risk for functional decline? Because that's actually going to be an important decision-making tool. Because then, we can talk to patients... We're like, "Yeah, I can tell you what your complication risk profile is. I can tell you what your cancer risk profile is. I can tell you what your quality of life and functional outcomes are going to look like." So that's what we're really working hard on right now.

Zach Klaassen: Excellent.

Sarah Psutka: And then the second part of that, of course, is how do you move the needle on that?

Zach Klaassen: Yes.

Sarah Psutka: And that's where the prehab story comes in.

Zach Klaassen: Let's talk about that. Because I think when you see these patients in the clinic... And we're not even talking age. You may see a 59-year-old guy's gone through chemo. How do you prehab that patient to get them ready for another big operation or another big hit, which is the operation?

Sarah Psutka: I start, actually, before they start their chemo. Because one of the questions, and you know this... Patient sits across from you, and they say, "Doc, what can I do?"

Zach Klaassen: Yes, you're absolutely right.

Sarah Psutka: "What can I do?" Because at that point, control's been taken away.

Zach Klaassen: That's right.

Sarah Psutka: We're dealing with a really tremendously terrible diagnosis.

Zach Klaassen: Yes.

Sarah Psutka: We're talking about not only... And we're talking about a long treatment path, three months of chemo, a month, a month and a half off, surgery, and then probably a three-month recovery, plus, plus, plus if we're talking about patients who are in their late 70s and 80s, which many of our patients are.

Zach Klaassen: Six, 12 months after surgery, yeah.

Sarah Psutka: Exactly. So we're talking about a protracted course. Patients say, "What can I do?" I say, "This is perfect time to quit smoking."

Zach Klaassen: Yes.

Sarah Psutka: Stop drinking... And then, I start talking about... So there's the stops.

Zach Klaassen: Yes.

Sarah Psutka: Stop doing the things that are going to make things harder, but then there's, let's create some really positive behaviors and make those part of your daily routine that are only going to make you stronger for surgery.

Zach Klaassen: Sure. Absolutely.

Sarah Psutka: So I try to keep it simple. I've spent a lot of time over the last couple of years deep diving the prehab literature and trying to learn from all the good work that other people are doing. I think one of the biggest problems that we see in prehab right now is, one, pragmatism, and two, scalability. So at the Bladder Cancer Advocacy Network Think Tank last summer, I ran a prehab breakout session. And overwhelmingly, the call from the patients was, why isn't this widely available? Why aren't people doing this everywhere? And the truth of the matter is, because we don't really know exactly how to do it yet.

Zach Klaassen: Yes.

Sarah Psutka: There are a couple of ideas we all have. But the other part of it was, we're asking patients to go a lot with through these treatments, and then you're going to ask them to go to the gym three times a week, and then you're going to ask them to start buying all these foods that may or may not be affordable.

Zach Klaassen: Sure.

Sarah Psutka: The financial toxicity piece of it is problematic because that gets into equity and the ability for people of all walks of life-

Zach Klaassen: That's right.

Sarah Psutka: To access this therapy. So I've tried really hard to think about, what's the low-hanging fruit? How can we do this in a way that is going to be feasible for as many people as possible, scalable, accessible, no matter where you live, and also not overly burdensome. So what we're doing right now, we just received funding from the Bladder Cancer Advocacy Network through their Clinical and Translational Trial Grant Award. And we're going to run a pragmatic prehab trial-

Zach Klaassen: Awesome.

Sarah Psutka: Over the next couple of years. The goal is to do a trial where we are asking patients to do personalized exercise prescriptions at home. So it's home-based. The exercise prescriptions are meant for them. So the other big issues with a lot of the prehab studies that are out there is that the folks who could get into those trials... It's like looking at clinical trial inclusion criteria overall. A lot of our patients would never make it into the trial.

Zach Klaassen: Totally.

Sarah Psutka: They're just too-

Zach Klaassen: You don't see ECOG zero on most invasive bladder cancer patients.

Sarah Psutka: Most of ours are-

Zach Klaassen: Yeah, exactly.

Sarah Psutka: Truthfully, they're like getting close to threes.

Zach Klaassen: That's right.

Sarah Psutka: And then, of course, we know from data from Chris Bergeron that, actually, they probably feel that their performance status is even worse than what we think it is because we-

Zach Klaassen: No doubt.

Sarah Psutka: We know that doctors tend to overestimate performance status.

Zach Klaassen: That's right.

Sarah Psutka: So we're talking about active interventions that can be done at home, that are personalized, even if somebody, for example, uses an assistive device. So we're not talking about high-intensity interval training. We're not talking necessarily about moving the needle on cardiopulmonary fitness and VO2 max testing. We're talking about balance. We're talking about core strength. We're talking about lower extremity strength, and some degree of endurance. The things that somebody who's going to have a big abdominal surgery-

Zach Klaassen: Yes.

Sarah Psutka: Needs to bolster in preparation for that operation and that hit, that stress. So we're going to do that, but the way that we're rolling out the trial is, we're using a really exciting piece of technology. It's a cell phone based application or smart device based application that interacts with our electronic health record.

Zach Klaassen: Cool.

Sarah Psutka: It's called ExerciseRx. It was built by my collaborators in our sports institute. And it basically allows patients to carry out these exercises and be monitored while they're doing them for adherence, but in a privacy protecting, non-video based way. It's at home. There's no additional cost. So we'll see... That's what we're working on. You asked me the good question of what do I do? Right now, it's pretty straightforward. I talk to them about doing these kinds of exercise. I do use our cancer rehab people and have patients go and get these personalized prescriptions. It's harder to monitor them without-

Zach Klaassen: Sure.

Sarah Psutka: A trial infrastructure. And then nutrition, I think, is critical.

Zach Klaassen: No doubt.

Sarah Psutka: But I keep it pretty simple there too. I talk about hydration, and protein supplementation, and good calories. Don't put anybody on a diet... Really talk about whole foods and trying to make changes that aren't overwhelming for people, so they're actually going to be sustainable.

Zach Klaassen: I think the key word here is pragmatic. And you mentioned that when you started talking about your grant. I think that's the key. Because as you mentioned, there's the neoadjuvant chemo. There's a recovery from that. There's a surgery, additional recovery. Key changes that are actually sustainable and not going to stress them, or the system, or the wallet. That's all important.

Sarah Psutka: Exactly. It's got to be doable.

Zach Klaassen: Has to be.

Sarah Psutka: And it has to be something... I think about that book, Atomic Habits, where you can stack positive changes.

Zach Klaassen: 1% every day.

Sarah Psutka: Yeah, exactly. If you just make one little bit of a positive change. But the nice thing is, a lot of this stuff actually makes people feel better too.

Zach Klaassen: Yeah, absolutely.

Sarah Psutka: So hopefully, they're positive things that folks can focus on while they're going through these treatments, that hopefully will also impact their, not only potentially candidacy for therapy, but also outcomes afterwards.

Zach Klaassen: Absolutely. No, that was fantastic. So just by way of wrap up, is there a couple of take-home messages you can give our listeners based on this excellent discussion we've had?

Sarah Psutka: I think the one part of all of this is, when we're talking to patients about treatments for cancer surgery, we talk to them about what we can do. I think a key principle of geriatric oncology, and this is something that I'm currently just an avid student of. I'm trying to learn to become a good geriatric oncologist, and I'm trying to learn from the people who do it really, really well. But a key principle of that is this whole idea of eliciting priorities and asking patients, what does a successful outcome look like to you?

Zach Klaassen: Great point.

Sarah Psutka: What matters? Because if it's length of life, that's one thing. If it's quality of life, that's another. And then what we need are these personalized risk prediction tools that can tell people what the short-term outcomes and the long-term outcomes are going to look like, so we can actually do a data-driven weighing of the options. And then theother part of it, I think, is you just partner with patients. And the nice thing about something like prehab, is I say it reassigns the locus of control.

Zach Klaassen: Yes.

Sarah Psutka: It takes that control from the cancer, puts it back in the court of the patient. Here are some really positive things that you can do, that you can engage the patients. And hopefully, my hypothesis is, we can improve the patient experience as they're going through treatment, which is really the survivorship experience.

Zach Klaassen: Yes, absolutely.

Sarah Psutka: So I think these data-driven a aspects of measuring risk are helpful. Hopefully, we collect a lot more data about the patient-specific outcomes that we don't have information on right now. And then at the end of the day, we come away with maybe even a more holistic way of helping these patients get through this treatment options.

Zach Klaassen: For sure. Congrats on the grants. We're excited to hear-

Sarah Psutka: Thanks.

Zach Klaassen: About these results in the next coming years. And hopefully not years, hopefully months.

Sarah Psutka: It's going to take some time.

Zach Klaassen: It's going to take some time. And we thank you for joining us today. It was a great discussion. Thank you, Dr. Psutka.

Sarah Psutka: Thank you very much.

Zach Klaassen: Thanks.