Ashish Kamat: Welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat from MD Anderson Cancer Center and I'm joined today by Dr. Samuel Washington, who is an Assistant Professor at UCSF in San Francisco. Dr. Washington is an Assistant Professor in the Department of Urology focusing on urological oncology, and he has a special interest in epidemiology and biostatistics, and specifically in health disparities research. And today, he's going to share with us his recent publication and data on how race modifies the survival benefit of guideline-based treatment and the implications for reducing disparities that we see in bladder cancer, specifically muscle-invasive bladder cancer for this topic today. So, Dr. Washington, the stage is yours.

Samuel Washington: Great. Thanks again for having me and allowing me to present our work that I did with Dr. Porten. Now we know for bladder cancer as a whole, it's a major contributor to cancer-related morbidity and mortality. And it's largely a disease that affects older individuals, those greater than the age of 50. In 2019, it was reported that approximately 158,000 incident cases would occur and 18,000 cancer-specific deaths. And we've seen similar numbers in 2020 based on our current age-adjusted estimates. But overall our knowledge of how the impact of disparities on the timing of diagnosis and outcomes such as survival remains limited. We know, broadly speaking, guidelines-based treatment based on AUA guidelines [inaudible 00:01:36] cystectomy with adjuvant or neoadjuvant chemotherapy or trimodal therapy in terms of surgical resection and maximal resection, radiation, and chemotherapy. We know that for African-American black patients with prostate cancer, we are seeing disparities both in terms of staging, as Black patients present with worse disease in all stages and worse survival at five years.

Now explaining the disparities, oftentimes we just focus on this being a product of access to care. And what that means, kind of varies based on the publication and what we discussed but, the caution and the thing that I always emphasize is that the people who do not have access to care are not included in the data sets that we are currently using. So we need to define this a little bit better. And then we need to figure out, is this due to access, but limited receipt of guidelines-based treatment. And looking at how these two things are related, we can better understand the effect of disparities in guidelines-based treatment and how that is impacting outcomes both across racial groups, but also within racial groups. Now for this study, our objective was to assess how the disparities and guidelines-based treatment mediate racial and ethnic disparities in survival for older patients with bladder cancer.

And we aim to really focus on the interaction between race and guidelines-based treatment in three specific populations, Black, white, and Latino patients with muscle-invasive bladder cancer. For this study, we use data from the National Cancer Database bladder cancer data set. This allowed us to look at data both at the individual level, as well as characteristics aggregated at the zip code level. Using this data in its format, we were able to do a hierarchical logistic regression analysis to cluster people based on correlations within facilities. So essentially, we adjusted for patterns within facilities that may not be reflected when we look broadly at the entire country as a whole. In addition, we adjusted for race, age, gender tumor characteristics, as well as clinical staging data. But we focused again on the interaction between the guidelines-based treatment and race in these models to understand how this disparity due to race may impact survival.

We found that of the almost 55,000 patients who were diagnosed with locally advanced muscle-invasive disease, 90% were white, 7% Black, and 3% Latino. The majority had cT2 disease, cNo/x nodal staging in urothelial carcinoma, for histologic diagnosis. Most were treated either at an academic center or a comprehensive cancer center, but overall we saw that only about half the patients were treated with guidelines-based therapies. When we compared those that received guidelines-based treatment to those that did not, we found that those that receive guidelines-based treatment were younger, white, diagnosed with urothelial carcinoma, privately insured, and treated at academic facilities. We found that when we looked at both race and guidelines-based treatment, the survival benefit of guidelines-based treatment was not the same for every group and not the same within each group.

So we found that on this graph here, Latino patients with guidelines-based treatment were found to have the best probability of survival in our adjusted models. We found that the white patients with guidelines-based treatment also had better survival probability compared to Black counterparts that received guidelines-based treatment. We see a similar pattern when we looked at patients without guidelines-based treatment. But the surprising finding was that when we looked at Latino patients that did not receive guidelines-based treatment, they had a higher survival probability compared to Black patients that did receive guidelines-based treatment. Now we saw patterns of mortality hazard when we looked carefully at this interaction between race and guidelines-based treatment. We found that Black individuals continued to have a higher risk of mortality compared to white and Latino counterparts. We found that the relative hazard, when we included the impact or survival benefit of guidelines-based treatment led to roughly equivalent mortality risk between our white and Latino patients.

Again, we found that guidelines-based treatment receipt for Black individuals equated to nearly equivalent hazards as Latino patients, without guidelines-based treatment. The interesting finding was that we found that guidelines-based treatment for Black individuals led to nearly equivalent mortality hazards as Latino counterparts without guidelines-based treatment. An unexpected finding that we have difficulty explaining fully with the data set used.

Now conclusions and next steps. We know that guidelines-based treatment is underutilized. This has been verified and validated by multiple data sets, but what we find is that it does not completely explain the disparities that we are observing in this study. We know that social determinants of health have a large impact on how care is received and outcomes after treatment. And that is a combination of multiple factors, including economics, food, security, education, healthcare, social, environmental factors, as well as environmental exposures. Now, this is also the result of systemic and institutional barriers to guidelines-based treatment.

But we know that they exist, although they were difficult or hard to quantify in this study. Qualitative studies to better understand the interactions, concerns, and experiences of people with muscle-invasive disease and how they interact in experienced care within the system can give us more insight into how to improve this. And examining the potential benefit of patient navigation, in other words, the ability to provide equitable assistance to allow people to navigate the complex healthcare system that we have now could prove beneficial to reduce some of these disparities. And lastly, we can't forget financial toxicity or burden in the carriers associated with the costs of healthcare, both direct and indirect, and how that may be perpetuating the disparities that we see currently. Thank you for allowing me to present this information.

Ashish Kamat: Thank you so much. That was a very interesting data set that you looked at and were able to come up with these conclusions. A couple of questions because obviously with the data set that you looked at, there are some limitations with the granularity of the data. Were you able to look and see whether the guidelines-based treatment incorporating chemotherapy, yes or no, also had an effect on the outcomes?

Samuel Washington: Yes. For this one, it was a great question. We actually kept our definition very broad. So other studies in the past have kept a tight interval of say 90 days between surgery and chemotherapy as a requirement. We were able to look at whether patients receive neoadjuvant or adjuvant chemotherapy, but lumped all of that together with if they received cystectomy to qualify as guidelines-based treatment. So if anything, our definition was broad and may create an overestimation of the utilization of guidelines-based treatment in this group.

Ashish Kamat: Yeah. And then what struck me was that, obviously, you are looking at disparities between Black individuals, white and Latino counterparts, but the guidelines-based therapy was only in half the patients overall, correct? And that sort of fits in with what we've seen in other studies from Europe as well. Any idea as to why that might be the case in the United States? And again, I know you can't say this from your data set, but just from all the work that you have done in this field?

Samuel Washington: Yeah. So I think it's hard again to know based on the data set. So I always hesitate to make causal inferences on the associations of this observational data, but I know just anecdotally that a lot of it has to do with healthcare resources, options that are discussed, and then on the patient side limitations at whether it's financial, concerns about the treatments and the impact on their family or time off from work. So I think all of these things may be impacting the rates of guidelines-based treatment that we are seeing, but not quantified in this data set. But I think also it's important to note that a lot of these factors may be things that are not dependent or focused on the individual, but more on the climate in terms of social climate and health care resources in that area that may be impacting guidelines-based treatment.

Ashish Kamat: Okay. I believe it is your group that has also done work on the discrepancies or differences between therapies within this African-American Black population. And in this paper, did you look at, or was it another paper that you had, where you looked at the differences between radical cystectomy and radiation therapy in the different groups?

Samuel Washington: Yes. So there was one, our prior paper, this was kind of a follow-up to that. We looked at guidelines based on appropriate treatment within the same institution, and we found differences based on race, even within the same facility, which was a little surprising. We did see differences in terms of the treatments received there as well. Again, we had difficulty kind of explaining why with the data set that we have, but this was really a follow-up to see how that disparity and treatment may impact survival differences that we are seeing here. Particularly in bladder cancer, where we know the survival is significantly impacted relative to say something that like prostate cancer, which has a much longer kind of observation period required to see a difference.

Ashish Kamat: Right. So I guess, the way I would look at your study is that essentially it shows us that guidelines-based therapy, the receipt of it essentially will modify some of the effects that we see of race on the survival of our bladder cancer patients. I mean, obviously, the impact varies from study to study, but overall there is a difference in the receipt of guidelines-based therapy. But once you take that into account, for the most part, at least from your data, it appears that the outcomes are in some ways equalized. Is that your sense as well, looking at your own data and other work that you've done?

Samuel Washington: I do agree. I think that the disparity that we are seeing, some that are due to the implementation of guidelines-based treatment. And we can at the very least reduce disparities, although it may not eliminate them completely. But I think the concept that we tried to focus on with this paper and the prior, was looking at race as a social construct, rather than solely biology. So I think in the past we've kind of attributed these disparities completely to biology. And I think our understanding now is that it is a combination of environment, exposure, and healthcare interaction and treatment that we are seeing these disparities. So I think again, by focusing on receipt of guidelines-based treatment, we can reduce those disparities.

Ashish Kamat: Yeah. And I think that is a very important point for our listeners and of course, patients as well, because there's different access to healthcare in different communities and it's based on so many different factors, but once the patient actually presents to a particular center, then providing the patient him or her appropriate guidelines-based therapy is one way to kind of get over the inequalities of access to health care that the patients might have faced in the first place getting to us at our centers of excellence. So yeah, I applaud you for bringing that point to the forefront. This has been a very interesting conversation and I want to give you the opportunity in closing to kind of leave our audience with one or two key points that you want to leave them with from your paper.

Samuel Washington: Yeah. Thank you for that opportunity. I think the key here is that we are seeing one, the underutilization of guidelines-based treatment, and two, that it may reduce disparity seen for locally advanced muscle-invasive bladder cancer. But that doesn't explain all of the factors. So I think when we see these patients in the clinic, understanding some of those factors that were not included in this analysis in the study are even more important. Because those may be the additional factors or kind of aspects of care that will make the difference for some of these patients.

Ashish Kamat: Right. Once again, thank you so much for taking the time from your busy schedule to share your thoughts and your presentation with us. Really appreciate it. Stay safe and stay well.

Samuel Washington: Thanks for having me.