FGFR 1–3 Alteration Frequency in Muscle-Invasive Urothelial Bladder Cancer and Its Effect on Prognosis

Background and Objectives: Fibroblast growth factor receptor (FGFR) alterations are therapeutic targets in urothelial carcinoma, but their prognostic significance in muscle-invasive bladder cancer (MIBC) is uncertain. We evaluated the frequency of FGFR1–3 alterations and their association with overall survival (OS) in Turkish patients with MIBC. Materials and Methods: Formalin-fixed, paraffin-embedded tumour samples from 194 patients with non-metastatic muscle-invasive (n = 154) or metastatic (n = 40) urothelial carcinoma of the bladder were analysed by targeted next-generation sequencing of FGFR1–3. Variants were classified according to ACMG/AMP tiers. OS was assessed with Kaplan–Meier and Cox regression analyses in the overall cohort and in both subgroups. Results: At least one FGFR alteration was detected in 131 patients (67.5%): FGFR3 in 42.8%, FGFR1 in 24.7% and FGFR2 in 20.6%. Most FGFR1 (91.7%) and FGFR2 (87.5%) alterations were Tier III variants, whereas Tier I FGFR3 hotspot mutations were found in 17.5% of the cohort. Median OS was shorter in FGFR-altered than in FGFR-unaltered patients (14 vs. 18 months; p = 0.024), with a similar difference in the non-metastatic subgroup (19 vs. 24 months; p = 0.047) but not in the metastatic subgroup (8 vs. 7 months; p = 0.653). After adjustment for metastatic status, ECOG performance status and age, overall FGFR alteration status was not an independent prognostic factor (HR 1.31, 95% CI 0.87–1.97; p = 0.200), whereas FGFR1 alteration was independently associated with worse OS (HR 1.62, 95% CI 1.07–2.44; p = 0.023). FGFR3 alterations were not prognostic. Conclusions: FGFR alterations, predominantly in FGFR3, are frequent in MIBC and are associated with shorter OS, but not independently of metastatic status and performance status. FGFR1 alteration was associated with poor prognosis, but this finding requires validation in larger cohorts.