Ashish Kamat: Hello and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urologic Oncology and Cancer Research at MD Anderson Cancer Center in Houston. And it's a pleasure to welcome today, Dr. Tullika Garg, well known to the field of bladder cancer, especially when it comes to her interest, both research and clinical wise in the care of our older patients, older adults. Dr. Garg's going to spend some time today talking to us about special considerations and Tullika, we are really looking forward to your talk. So with that, the stage is yours.

Tullika Garg: Thank you. Thanks, Dr. Kamat. Cancer is a condition of aging. By 2030, we are going to see an incredible increase in new diagnoses in older adults over the age of 65. According to Sierra Medicare, we're going to see an increase of 67% in the older population by 2030. And this graph kind of demonstrates some of that data specifically showing this gray line and the rapid rise that we are going to see. And bladder cancer specifically disproportionately affects older adults. It has the highest median age of diagnosis of all cancer sites, 73 years, and the peak of diagnosis is in the age or greater than 80 years, 179 cases per hundred thousand. We're going to see a projected increase of 68% of bladder cancer incidence in older adults by 2030. And as many of us know, these patients have high rates of multimorbidity and in some work that we've done previously, we found that older adults with bladder cancer have a median of eight chronic conditions coexisting with their bladder cancer.

Our older cancer patients are different from our younger counterparts and mostly because they have geriatric conditions. And this is just a listing of some different geriatric conditions that we can evaluate for in our older adults when they're diagnosed with cancer, including functional status, falls, cognitive impairment, multimorbidity with is defined as the presence of two or more chronic conditions, nutritional issues, depression, and specific to urologic oncology and bladder cancer, they tend to have incontinence and other urinary issues. And we know that cancer treatment worsens these geriatric conditions. So patients following cancer treatment, survivors report, they have poor physical function, they have worse quality of life, they have more chronic conditions. On average, they're diagnosed with an additional two chronic conditions following their cancer treatment, as well as cognitive decline due to the treatment, specifically chemotherapy.

Our older cancer patients are also different from younger counterparts because they have different goals as they embark on treatment. For example, in this survey study of seriously ill patients who are older adults with cancer, they found that patients would rather die than undergo a treatment that would cause functional impairment or a cognitive impairment and at very high rates. So understanding goals and healthcare preferences is really important as we consider cancer care for older adults. And as you can see, goal elicitation is a cornerstone of many different guidelines from different professional organizations, including the American Urological Association, the National Comprehensive Cancer Network, ASCO, the American Geriatric Society, and the American College of Surgeons, and the Institute for Healthcare Improvement.

So when we're considering geriatric conditions and goals and what we're balancing when we're talking to our older patients about their cancer treatment, so we're trying to decide about undertreatment or overtreatment. And what that involves is understanding who is a fit older adult, and who's a vulnerable older adult. And so undertreatment would be considered less intensive treatment in somebody who could tolerate more intensive treatment. And over treatment is intensive cancer treatment in somebody who would be vulnerable and who would benefit from having less intensive therapy. So I'm just going to switch gears and talk a little bit about some considerations, both for non-muscle invasive and for muscle-invasive bladder cancer.

So when we're thinking about non-muscle invasive bladder cancer, one of the cornerstones of our diagnosis and treatment is transurethral resection of bladder tumor. And I think it's important for us to remember that TURBT is not necessarily minor surgery for older adults. It requires general anesthesia and these repeated anesthetics can be very difficult for older adults, specifically, as we know more and more these days, that repeated anesthetics are associated with worsening cognitive impairment, as well, these patients can suffer from delirium postop, which also has long-term effects on cognitive impairment. And as we knew from the prior slides, a lot of older adults would not elect treatment that would result in cognitive changes. In addition, these patients have to manage taking care of a catheter at home and maybe have some burdens on caregivers as a result. And there are also some major and minor complications, as you can see from this study that was done in the NSQIP database, a large TURBT has significant complications on the order of almost 20%.

And this is just a quote from a patient of mine who participated in a focus group that we published back in 2018. This patient said that "Ever since surgery, I feel a little differently, like not my normal self, kind of walking around in a dizzy state."It's also important to remember that non-muscle-invasive bladder cancer is an incredibly burdensome chronic condition of its own right and has a very high recurrence rate of 30 to 70% with a low risk of death. And we need to consider all of those visits that we do for non-muscle invasive bladder cancer within the larger scope of these patients, other median of eight chronic conditions. So this is just from the AUA guidelines for non-muscle invasive bladder cancer, showing the number of treatments per year for somebody who is diagnosed with low intermediate, and high-risk disease. We can see with the intermediate and high-risk disease, just for the bladder cancer treatments and cystoscopy alone, they can have up to 19 visits per year, and that excludes surgery, recurrences, preop visits, path discussions, et cetera.

So some different things to think about when we're caring for older adults with non-muscle invasive disease are tailored surveillance schedules based on some of their geriatric conditions, thinking about their other chronic conditions, and the burdens that they may be managing due to things like heart disease or diabetes or COPD, what other competing risks they have in terms of life expectancy. And also we need to consider the goals and healthcare preferences of our older adults. There are more studies coming out about active surveillance for low-risk non-muscle-invasive bladder cancer, which could reduce the risk of anesthetics for these older adults. Also considering office fulguration and biopsies for small recurrences. It's also important to think about intolerance to intravesical therapy and I think this is an area where we need more research and understanding about how intravesical therapies affect our older adults who may already have baseline urinary dysfunction.

And then each recurrence for bladder cancer is a new decision point. And as patients change over time, it's important to have these iterative discussions about goals and healthcare preferences. So shifting gears to muscle-invasive bladder cancer, and of course the standard of care for treating muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy. And we know also that our older adults tend to receive less potentially curative therapy for muscle-invasive disease. And we don't fully understand why, but one of the considerations for these major treatments is determining who is fit and who is vulnerable. And the idea here is to avoid undertreatment for those who are fit and avoiding overtreatment for those who are vulnerable. So there are many different tools available for trying to assess fitness for chemotherapy or for surgery. There are chemotherapy toxicity risk calculators, and also screening tools that can be used to identify geriatric conditions or to identify patients who may benefit from a geriatric assessment.

And so when we're thinking about different aspects of optimizing older adults for bladder cancer treatment if we identify risk of toxicity or if we identify other geriatric conditions on screening, it's important to think about treatment tolerability and whether the patient would be able to go through with treatment, adhere to treatment, whether it's chemotherapy or what their long-term functional outcomes may be from radical cystectomy. And so there's increasing evidence for geriatric assessment-guided interventions to optimize different geriatric conditions. And also from a surgical standpoint, perioperative management and potentially geriatric co-management both pre and post-op can be helpful. And of course, we always come back to discussion of goals, and healthcare preferences remain central because we need to understand that the goals of our older adults is different from the younger counterparts. So this is just one example of a tool that can be used to assess risk for older adults and try to understand whether somebody is fit for chemotherapy.

This is the Cancer and Aging Research Group, a chemotherapy toxicity calculator. It is publicly available online, and it uses a very simple scoring system and with several different variables. And I just want to call attention to the fact that GU cancers are considered higher risk and I think part of that is because of the type of chemotherapy that is used for GU cancers and also potentially the older age of patients who have GU malignancies. So this is something very simple that you can do in clinic, add up the score, and then you can use this to interpret what the risk is of developing grade three to five adverse events from chemotherapy. And this is something that can be used in counseling an older adult who's considering neoadjuvant chemotherapy.

And then when thinking about cancer surgery for older adults, and of course, radical cystectomy is an enormous surgery that these patients undergo and has significant impact on quality of life downstream and so optimizing our older adults is a really important part of the both preoperative, operative and postoperative management. So from a preoperative standpoint, this is just a simple framework for thinking about different aspects of optimization for older adults and from a preoperative standpoint, it's important to consider frailty screening or identifying different geriatric conditions or potentially identifying patients who may benefit from a more formal geriatric assessments, prehabilitation, whether that's exercise or nutrition. And then of course shared decision-making in the context of goals and healthcare preferences.

And then during the surgery itself, there's increasing evidence from the colorectal literature that minimally invasive approaches can be helpful for older adults and can help to reduce the risk of worsening of geriatric conditions and other adverse events. And then using enhanced recovery pathways intraoperatively is also helpful. And then from a postoperative standpoint, there are some studies coming out about geriatric co-management and how having an in-house geriatrician assisting with the management of patients over the course of their hospitalization can be helpful and provide a different lens for how these patients are managed involving rehabilitation services, physical therapy, occupational therapy, both enduring hospitalization, and potentially at discharge. And it always important to incorporate social support and caregiver support throughout the process as they're going to be the main point person for the patient.

So in conclusion, bladder cancer incidence in older adults is rising. And whether we like it or not, all of us are going to become geriatric oncologists taking care of these patients. Our older adults with cancer are different from younger counterparts and it's important to think about their management in the context of geriatric conditions and their goals in healthcare preferences. In non-muscle-invasive bladder cancer, we need to consider the long-term ramifications of TURBT on these patients, both in terms of their cognitive function and their urinary function. Treatment burden from all of the visits related to managing non-muscle invasive disease and tailored surveillance and treatment schedules. In muscle-invasive disease, there are many existing tools that can be used to identify fit older adults and optimize treatment based on geriatric conditions that are identified over the course of preoperative and pre-chemotherapy evaluation. And of course, it's important for all of us to discuss goals and healthcare preferences with our patients. Thank you.

Ashish Kamat: So thanks so much Dr. Garg. I mean, that was a very nice comprehensive overview of the topic that you hold so near and dear to your heart. You covered a lot of ground. Let me ask you just a couple questions for the benefit of our audience. The first is, in your opinion in view and review of the literature and trials that are being reported on right now, what do you think we as a community should be doing and I'm going to say we as a community investigator and pharma for that nature when it comes to appropriate representation of our older patients in the actual design of clinical studies?

Tullika Garg: Yeah, I think that's a great question. And of course, older adults are not well represented in clinical trials and that's been an ongoing issue. And I think there's a couple different ways to approach that, and one is that I think we need to consider our criteria for involving older patients in our clinical trials. Sometimes the criteria can be more restrictive out of concern for adverse events. I think particularly for renal function, for other chronic conditions and functional status. I think also potentially pragmatic trials may offer a new avenue for considering more real-world management of older adults and kind of meeting them where they are rather than having a more formalized clinical trial approach. So I think that may be one way to also utilize our older adult population to better understand what the impact of our treatments are. And I think trials should incorporate endpoints that are also important to older adults, not just recurrence and progression, but also consider things like functional outcomes, urinary outcomes, other quality of life aspects.

Ashish Kamat: Yeah, no, I'm glad you brought that up because of what's relevant or important to someone in their 40s might not be as important to someone in their 80s or 90s. And conversely, they may be aspects that we don't factor in that are real issues that our patients face. If for example, a treatment is every two days, sometimes our patients don't have access, their caregivers can't drive them to the doctor's office twice a week for those sorts of treatments. With that in mind, do you have any tips again for our caregivers or patients that might be listening to this right now as to where people can access, and when I say people, I mean, from the patient perspective, where information is available for them to access in ways in which they can overcome some of the hurdles that they might be facing that we can't really help them with one-on-one?

Tullika Garg: Yeah, absolutely. I always encourage our caregivers to come to appointments, to ask a lot of questions to advocate for their care recipient as much as possible. I worry personally when there isn't a caregiver there or if the caregiver remains quiet throughout the appointment. I think there's some wonderful resources through the Bladder Cancer Advocacy Network. They have recently published information packet specifically for caregivers. I think that's been really helpful to some of our patients. I think bladder cancer support groups are wonderful for caregivers as well. I think they have an opportunity to know that they're not alone in the caregiving experience. And then, I think there's wonderful resources on the internet that are really patient and caregiver-directed materials through other organizations like the National Comprehensive Cancer Network. I think there's a lot of materials out there, but I think first and foremost is making sure to advocate and ask and not be afraid to speak up.

Ashish Kamat: Again, very important point, I think sometimes we, as physicians need to remember to include the caregivers in the conversation. Obviously, if they're there in person it's easy to do, but especially during the times of the pandemic, at least in our center, visitors couldn't come in with the patient. And I would always make it a point to say, "Hey, get two or three people on the teleconference, I don't mind listening to static in the background if I have to," because it will help our patients get better access because they'll be able to convince their caregivers as to what the doctor said, rather than it being transmitted second or third hand. But more importantly, I'm able to then address questions upfront and in some ways feel the telephone calls that would come later to my office where they may not have been privy to the conversation. So excellent points that you raised. This is such an important topic you and I could chat and I know we have in the past, talked about this for a long time, but in the interest of time, let me sort of hand the stage back to you and maybe leave our audience with some high-level thoughts that you'd like them to kind of take home as a take-home message.

Tullika Garg: Yeah, I think first and foremost, I think caring for older adults with bladder cancer is truly a joy. I mean, I think it's wonderful to be able to be with them on that journey. I think it's really important to recognize that these patients are different from our younger counterparts and we need to have a healthy appreciation for these geriatric conditions and for the different goals and healthcare preferences that they have. And I totally agree that involving caregivers as a key part of the healthcare team is really central to helping our older adults to thrive through their bladder cancer treatment.

Ashish Kamat: Right, thank you again, Tullika, for taking the time and spending it with us and stay safe, stay well, and hopefully we'll see each other in person again soon.

Tullika Garg: Thank you, you too.