Tumor profiling of advanced urothelial carcinoma: Comparative analysis based on social determinants of health.

Abstract

Background: Studies on the genomic characteristics of urothelial carcinoma (UC) patients from diverse backgrounds are scarce. Herein, we sought to characterize genomic landscapes of advanced UC in a regional representative cohort to examine the possibility that patients from different backgrounds may have socioeconomic-influenced molecular changes.

Methods: We retrospectively evaluated clinical and genomic findings of UC patients presenting to the University of Arizona Cancer Center (Tucson, AZ) from 2016 to 2023. Molecular profiles were obtained using DNA next-generation sequencing (Caris Life Sciences) and stratified based on Area Deprivation Index (ADI) collected from each patient residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage.

Results: Among 97 patients, 43 resided in low ADI areas and 54 in high ADI areas. Higher Hispanic ethnicity (P = 0.011) and lower mean household income (P < 0.001) were seen in high ADI areas. There were no differences in microsatellite instability, loss of heterozygosity or PD-L1 expression. Patients from high ADI neighborhoods had lower TMB scores (62.7 % vs. 51.3%) when compared to low ADI neighborhoods (P = 0.291). The genes with higher rates of alterations when comparing low vs high ADI areas were PIK3CA (20.9% vs. 16.7%, P = 0.610), TP53 (62.8% vs. 40.7%, P = 0.041), KDM (18.6% vs. 22.2%, P = 0.802), ARID1A (20.9% vs. 25.9%, P = 0.636), and TERT (41.9% vs. 35.2%, P = 0.674). A high rate of immunotherapy use (66.7%) and clinic trial enrollment (73.3%) was noted in high ADI patients. There were no overall survival differences between the groups.

Conclusion: Few genomic differences were seen based on socioeconomic status. Lower rates of TP53 alterations and low TMB were seen in patients from disadvantaged neighborhoods. Neighborhood-level factors potentially leading to cancer disparities warrant investigation.