Fibroblast Growth Factor Receptor 3 Mutation as a Prognostic Indicator in Patients with Urothelial Carcinoma: A Systematic Review and Meta-analysis

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) mutations have been implicated in urothelial tumorigenesis. FGFR3 inhibitors are being explored in clinical trials. OBJECTIVE: We aimed to study the association between FGFR3 mutations and survival in urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: We performed a systematic literature search of PubMed, Cochrane, Ovid, and Web of Science from January 1985 to October 2018. The search terms were as follows: targeted therapies, FGFR and its subtypes, urothelial, bladder, and cancer. We included case-control or cohort studies of FGFR3 mutations in urothelial carcinoma. We included studies reporting hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes comparing FGFR3 mutations with FGFR3 wild type. Two reviewers performed article selection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed heterogeneity among study-specific HRs using I(2) statistic. We used a random effect model to obtain HR and 95% CI for event-free survival (EFS), composed of recurrence-free and progression-free survival. Statistical tests were two sided. RESULTS AND LIMITATIONS: Eleven studies (seven retrospective and four prospective) comprising 2162 patients were included. Analysis was performed for two groups. The first group included 1651 patients with non–muscle-invasive (NMI) urothelial carcinomas (886 [53.6%] had FGFR3 mutations). Compared with FGFR3 wild type, FGFR3 mutation did not influence EFS (HR = 0.99, CI = 0.77–1.28, p = 0.96). There was no significant heterogeneity (I(2) = 25%). The second group included 511 patients with NMI and muscle-invasive (MI) urothelial carcinomas (151 [30%] had FGFR3 mutations). FGFR3 mutation was not prognostic (HR = 1.54, CI = 0.41–5.81, p = 0.52). There was heterogeneity (I(2) = 91%). CONCLUSIONS: There is no association between FGFR3 mutation and EFS in NMI urothelial carcinoma, and in NMI and MI urothelial carcinoma groups. PATIENT SUMMARY: Fibroblast growth factor receptor 3 (FGFR3) mutation is not associated with a worse survival outcome in urothelial carcinoma. This is important as FGFR inhibitors are emerging as a new treatment option.