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Sam Chang: Hi, I'm Sam Chang. I'm a urologist at Vanderbilt University in Nashville, Tennessee, and we have the privilege of having Dr. Jason Brown, who's an assistant professor at the University Hospitals, the Seidman Cancer Center, who has done some work looking at an increasing problem that I think we're starting to understand a little bit better. His study focuses on disparities in bladder cancer mortality differences between urban and rural settings. It's an analysis that covers about a 20-year time period. Dr. Brown, thanks so much for spending some time with us on UroToday, and we look forward to your presentation. I think you have some slides to present going over the work that you all have put together.

Jason Brown: Thanks, Sam, for having me. As he said, I'm Dr. Jason Brown. I'm an assistant professor at University Hospitals Seidman Cancer Center. Today, I'm going to talk about our poster from ASCO this year, on disparities in trends in bladder cancer mortality between urban and rural patients between the years 2000 and 2020. For an outline of the topics that I'll discuss today, I'll talk about the methodology that our team used, trends in bladder cancer mortality by location, as defined by large metropolitan areas, all the way down to small rural areas, and how these trends in bladder cancer mortality actually changed over the years in each of these types of locations. Disparities are an important topic in the study of bladder cancer. A lot of the studies today in disparities have looked at racial disparities or socioeconomic disparities, but our team wanted to look at differences in mortality between the urban setting and the rural setting.

To do this, we used the publicly available CDC Wonder Database. We looked at age-adjusted bladder cancer mortality. We looked at the average annual percent change between the years 2000 and 2020 to have a well-defined time period in which a lot of changes have happened to bladder cancer treatment. We also used a model called Joinpoint Regression to look at the individual changes per year to see exactly when in that period changes happened over time. The map on the right of the screen shows the distinction between various areas by county in the United States, ranging from, in the red, large central metro areas, all the way to what are considered rural or non-core areas. In between, there's the large fringe metro, which are also known as the suburban areas, the medium metro area, more of the exurbs, and then smaller metro, micropolitan, and finally, the rural areas.

With the six categories of location, we looked at the average annual percent change over the 20-year period. The largest change was seen in the large central metro area with a 1% decrease in age-adjusted bladder cancer mortality. Similarly, decreases in mortality were seen in the larger metro areas, including large fringe metro and medium metro areas, but this was not seen in the small metro, micropolitan, or non-core rural areas. We also looked in the Joinpoint analysis to see if there was a cut point within this period in terms of a greater decrease in this mortality. We did find around 2016, for the large central metro area and large fringe metro areas, that there was this change and the change occurred in 2017 in the medium metro areas, whereas the bladder cancer mortality was stable in the small metro and rural areas.

Looking at this Joinpoint analysis more closely, look at the six different colors here which represent each of the different types of urban to rural areas. A change in the mortality was modeled using this Joinpoint Regression model. As you see, even in the large metro area, which was the blue one on the bottom, mortality was fairly stable between 2000 to 2016 and had a much sharper decrease from 2016 to 2020. Similar but not as stark, trends were still seen in the large fringe metro and the medium metro areas, whereas no change was seen in the small metro, micropolitan, or non-core rural areas. Based on this, we found that there was a greater decrease in mortality in the urban compared to the rural settings, so why might this have been?

Well, around 2016, this decrease was accelerated but only in the urban settings. That was around the year that immunotherapy was approved. Could this be a potential impact of advanced treatments? Of course, we have to also take into account potential other confounding factors including access to care, the environment, patient socioeconomic status, and ultimately, adoption of clinical guidelines, which can all contribute to differences between urban and rural settings. The take-home message of this presentation is, between 2000 and 2020, bladder cancer mortality significantly declined in urban areas with the largest decrease seen in the large central metropolitan areas. However, in rural areas, bladder cancer mortality rates remained unchanged over the same period, showing a stark difference between these two geographic populations. Thank you very much.

Sam Chang: Jason, thanks so much. This work obviously raises a lot of questions, but I think people want to go first into, okay, you've got different possible hypotheses on contributing factors regarding these differences. Tell me what you really think is going on. Is this something where that leveled mortality, if you go back another 20 years, let's say from 1980 to 2000, do you think it was flat then? This is hypothesis only. This is not evidence-based, but I would love to know your thoughts as you've really looked at the numbers. You've really gotten an idea of the differences that really show this disparity in outcomes. Tell me your thoughts on why, and then tell me your thoughts on is this a trend that's going to either precede this or is this going to continue to actually show differences from 2020 and beyond?

Jason Brown: Yeah. Thanks, Sam, for that question. When we look at mortality, bladder cancer affects a lot of patients, but the mortality really comes from advanced disease. When we're looking at patients who died of bladder cancer, we're looking for potential changes in management of advanced disease or how patients get advanced disease, and especially because 2000 to 2016, everything was remarkably stable. If you think about how we treated bladder cancer, especially metastatic bladder cancer, over those years, essentially, we had one tool, platinum-based chemotherapy. In 2016, that was when everything started to change with immunotherapy. But we also know that adoption of new treatments is somewhat slow, and we have data from many individuals that have shown that, in not just bladder cancer but in other diseases.

What I imagine is that patients who had more access to care, more access to specialists that focused on bladder cancer, that they were able to reap the benefit of these novel therapies and potentially even clinical trials sooner than those who lived farther away from either these large academic medical centers or even places that had access to treatments, because a lot of places still may not have access to some of the treatments. In the future, it'd be interesting to see what happens in 2023 after this rapid seismic shift that we've had in our first-line treatment with EV and pembrolizumab. We know that there are a lot of communities that are still having difficulty getting this regimen, and for places where they do have access to it, is it being used nearly as often? Whereas patients who go to larger medical centers or live in these larger metropolitan areas and have more access to care might be receiving this more.

It'd be interesting to redo this analysis, let's say, a decade down the road and see, around 2023, did we see another sharp change? What my hope is that, in the future, when we look at the rural areas, we will eventually see this change, but potentially just a few years lag behind. We did look at a few other diseases including prostate and kidney cancer, and we actually did not see as much of a change over the 20-year period. This was more unique to bladder cancer.

Sam Chang: That's definitely interesting. It may be that the changes in prostate or kidney cancer, there are changes but perhaps the new regimens may not be as impactful or it'll take longer to see these survival differences, but it'd be interesting to tease out. As you look at that, the differences, educate me, and you may or may not know this answer, but with other disease processes, say diabetes or hypertension or heart disease, are there similar differences in mortality between the urban and the rural areas? I would like to know, because I think, overall, you would assume that the level of care perhaps isn't as high in the rural areas vis-a-vis the urban areas.

Jason Brown: Yeah. I don't know the data, so a lot of this will be conjecture on my part, but I imagine that there is probably higher mortality also in those areas as well. It's not just that those areas don't have the knowledge or expertise, have access to the newest treatments, but also the difficulty in accessing care. The other thing is that patients in these areas, it's not... You go down the street and see your doctor or drive 10 minutes. A lot of these patients have to travel a lot further. We sometimes see this, even patients who get transferred from these rural settings, to the hospital. Initially, you have the frustration like, "What is their doctor doing?"

It's a tough task to be a doctor in these more rural areas because you have to know basically everything. A lot of these areas, you are the doctor. For me, I need to know bladder cancer well, maybe prostate and kidney cancer. But beyond that, I don't need to know anything about breast cancer, about lung cancer, and be at the forefront of that. Especially with some of these seismic shifts that we've recently seen in bladder cancer, it's our job to get that word out.

Sam Chang: Right. No, I think that's essential. Where next research-wise, Jason? Where are you guys going to go next in terms of this evaluation? You've already looked at some disease processes. Are you going to hone in on certain characteristics? Are you going to start looking at other databases with data? Where next in terms of research?

Jason Brown: Yeah. In regards to this project, I think we're going to really focus on bladder cancer and look at maybe some of these potential confounders. Does race play a big role? Socioeconomic status? One of the things we're actually looking at is the median income of each state and potentially even at the county level, although we may not have enough cases in terms of mortality for some of those smaller rural counties that have fewer patients, but to see if this ties into that, and then also looking at the impact of having health insurance. As I mentioned, the access to care. On this database, they also list by county the percentage of patients that are uninsured. I imagine that would be higher in the rural counties than the urban counties, but we'll look at potential other barriers to care and other things that we may be able to overcome.

Sam Chang: Yeah. I think a lot of people conjecture hand in hand that the income, the lack of insurance, etc., would go hand in hand and support that difference in access to care, access to quality care, etc. It's a lot of food for thought, because the duty for all of us then is what do we do? How do we take the next steps in terms of policy to help decrease these differences in levels of care? It's a possibility that, really, there's not much we can do in terms of being able to provide... We want to provide everything equally to everyone, but that ability is definitely going to be difficult, especially for some of these more expensive, more time-intensive, labor-intensive treatments.

It really is a difficult question to tackle, but recognizing, I think, is the first step, and we're starting to recognize that. The next step is obviously taking steps to, hopefully, then counteract these differences. Jason, thanks so much for spending some time with us and helping to really put a spotlight on these differences, not necessarily in terms of even access, but really the bottom line that there are differences in mortality. I think that's an important message to get out there so that people understand. We look forward to future research projects from you and your group.

Jason Brown: All right. Thank you very much.