Prognostic impact of FGFR3 molecular profiling in high-grade T1 bladder cancer

Abstract Background Fibroblast growth factor receptor 3 (FGFR3) has long been implicated in the molecular pathogenesis of non-muscle invasive bladder cancer (NMIBC), yet its prognostic value is controversial. Molecular heterogeneity could explain the highly variable clinical outcomes in high grade T1 (HGT1). Objective To determine whether FGFR3 mutations, gene expression and protein expression are associated with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with primary HGT1 bladder cancer. Methods We retrospectively included 87 patients with primary HGT1 bladder tumors. FGFR3 mutational status, gene expression and protein expression were assessed by Sanger sequencing, reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry, respectively. RFS and PFS curves were estimated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. Cox proportional hazards regression models were constructed adjusted for European Association of Urology NMIBC risk group. Results FGFR3 mutations and protein overexpression were observed in 33 (38%) and 31 (36%) cases, respectively. Mutation status was strongly associated with protein expression, with an OR of 6 (95% CI 2.35–16.3, p < 0.001). In univariate analysis, FGFR3 protein overexpression was associated with worse RFS ( p = 0.03), while FGFR3 mutations ( p = 0.02) and gene overexpression ( p = 0.02) were associated with improved PFS. In multivariate analysis, only FGFR3 protein overexpression was independently associated with worse RFS (HR 1.98, 95% CI 1.08–3.63; p = 0.02). Conclusions In this retrospective single-center cohort, FGFR3 molecular measures showed distinct associations with recurrence and progression outcomes. These exploratory findings support further evaluation of integrated FGFR3 profiling in larger, independently validated cohorts before routine clinical implementation.