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

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. 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. 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. 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.