Pathogenic germline variant prevalence and genetic testing outcomes in patients with urothelial carcinoma.

• DOI: 10.1200/jco.2025.43.5_suppl.741
• Publication Date: 2025-02-18T14:38:27Z
• Authors: Eugene Oh; Piroz Bahar; Ye Chua; Marie-Louise Accardo; Xiaochen Li; Erika Koeppe; Phillip Lee Palmbos; Irene Tsung; Zachery R Reichert; Ulka N. Vaishampayan; Tobias Else; Charles B Nguyen
• Keywords: Urothelial cancer

741 Background: Urothelial carcinoma (UC) is rarely attributed to hereditary causes, but recent studies suggest inherited factors may play a larger role. Current guidelines recommend considering genetic evaluation in patients with bladder cancer diagnosed at <50 years old or personal family history of Lynch Syndrome-associated cancers. However, the full pathogenic germline variant landscape and optimal criteria UC remain poorly understood. In this study, we report testing outcomes clinicopathologic characteristics who underwent evaluation. Methods: A retrospective analysis all University Michigan Cancer Genetics Clinic between 2002 2024 was performed. Patients did not have diagnosis code undergo were excluded. Genetic outcomes, prevalence characterization, associated features recorded. Fisher’s Exact test used compare individuals found likely (PV/LPV) vs. those negative uninformative testing. Results: Among 151 referred genetics, 129 Median age 59 (IQR: 48-68). Most (58%) had non-muscle invasive disease initial diagnosis; 26% muscle disease, 9% metastatic 7% unknown. Pure urothelial histology most frequent (71%). majority (83%) primary tumor location bladder. The common reasons for referral counseling multiple cancers (58%), perceived younger (19%), suspicion syndrome based on syndromic (9%). tested patients, 35 (27%) confirmed PV/LPV; 18 (14%) unknown significance (VUS) only. PV/LPV genes MSH2 (n=8, 6%), BRCA2 (n=5, 4%), CHEK2 (n=4, 3%), APC MUTYH 3%). There no statistically significant differences (<65 vs >65, p=0.83; <55 >55, p=0.16; <45 >45, p=0.61), location, stage diagnosis, other cancers, first-degree cancer. Oncoprint visualization will be presented. Conclusions: genetics testing, 27% PV/LPV, although cohort selected population. Age threshold traditional results. These findings broader use UC. Future should determine given impact cascade potential therapeutic implications.