Genomic profiling in bladder cancer across a spectrum of measured socioeconomic inequality: A retrospective review utilizing next generation sequencing.
Authors: Kenneth Barker, Denis Ruzdija, Aaron Bertolo, Irasema Concepcion Paster, Jose Guillen-Rodriguez, Ricardo J. Estrada-Mendizabal, Juan Chipollini, Alejandro Recio-Boiles
Journal: Journal of Clinical Oncology (2024)

545 Background: Socioeconomic inequality (SI) is a known risk factor for worse prognosis in bladder cancer. The mechanism behind this is likely due to a complex interplay between many factors including access to care, diet and exercise disparities, and frequency of tobacco/alcohol use. There remains a scarcity of studies looking at the impact of socioeconomic inequality on tumor biology in bladder cancer, yet genomic profiling to look for biomarkers with therapeutic targetability is becoming increasingly common through testing modalities such as next-generation sequencing (NGS). This study aimed to further understanding of the effect of SI on the genomic alterations with therapeutic implications seen in bladder cancer. Methods: This was a retrospective analysis of 108 patients (75 male and 33 female) ranging from 18-92 years old with bladder cancer presenting to the University of Arizona Cancer Center from 2016-2023. Of these 108 patients, 97 had NGS data available. Each actionable pathogenic mutation, tissue mutational burden (TMB), and combined positive score (CPS) for PDL1 expression was recorded for each patient. TMB score of &gt;10 and/or CPS of &gt;10 were considered as actionable mutations for immunotherapy. The Area Deprivation Index was used to measure SI levels of each patient’s neighborhood based on a national scale from 1-100 with 100 being most disadvantaged and 1 being the least. These patients were then split into three tertiles: 1-33, 34-67, and 68-100 to compare the frequency of genomic alternations using chi-squared for contingency tables and kruskal-wallis rank test for multiple samples. Results: Of the 97 patients with NGS, 18 were in tertile 1, 47 in tertile 2, and 34 in tertile 3. TMB-High&gt;10 was significantly different between tertiles with the following frequencies of TMB &gt;10: tertile 3 8/34 (23.5%), tertile 2 21/47 (44.6%), and tertile 1 10/18 (55.5%), (p=&lt;0.05). The mean mutational burden in tertile 1, 2, and 3 was 11.3, 10.17, and 8.22 respectively (p=0.147). There was no correlation of SI with the selected frequent mutations KDM, ARID1A, TERT, TP53, PIK3CA, TP53, and TERT (p&gt;0.05). Conclusions: Higher TMB in bladder cancer has been associated with a more favorable prognosis and predictive response to immunotherapy. Our results show patients from neighborhoods of higher SI have a significantly lower frequency of TMB score &gt;10, and this could offer partial explanation for the worse prognosis seen with higher SI levels. Our relatively small sample size limits the power of our study. Further investigation through larger scale studies of the genomic alterations seen between SI levels have important implications in understanding both why and how to better address the worse outcomes seen in bladder cancers in patients with greater SI levels.