FGFR3 Gene Alterations and Protein Expression in Paired TURBT and Radical Cystectomy Archival Specimens of Muscle-Invasive Bladder Cancer

This study investigated whether neoadjuvant chemotherapy (NAC) influences the detectability of fibroblast growth factor receptor 3 gene alterations (FGFR3alt) in muscle-invasive bladder cancer (MIBC). Among 173 patients who underwent radical cystectomy (RC), 70 had paired transurethral resection of bladder tumor (TURBT) and RC archival specimens available for FGFR3 RNA testing and immunohistochemical (IHC) analysis. FGFR3alt were detected in only six tumors (8.6%), and 13 RC specimens (19%) showed RNA test failure, predominantly in archival samples older than 10 years. The assay-success concordance of FGFR3 RNA test results between paired TURBT and RC specimens was high (73%), although one NAC-treated patient with FGFR3alt TURBT tissue converted to FGFR3-negative status in the RC specimen. IHC analysis demonstrated significantly higher FGFR3 protein expression in FGFR3alt tumors and a moderate correlation between paired TURBT and RC specimens, irrespective of NAC exposure. Because FGFR3 alterations were detected in only a small number of cases, the study was underpowered to evaluate whether NAC influences FGFR3alt detectability. These findings underscore the need for validation in larger, multi-institutional datasets and integrated molecular profiling to clarify the impact of chemotherapy on FGFR3-driven bladder cancer biology.