Fibroblast Growth Factor Receptor 3 Mutation as a Prognostic Indicator in Patients with Urothelial Carcinoma: A Systematic Review and Meta-analysis
Sidra Khalid, Bassam Basulaiman, Jeffrey Emack, Christopher M. Booth, Ignacio Durán, Andrew Robinson, David M. Berman, Martin Smoragiewicz, Eitan Amir, Francisco Vera-Badillo
Abstract
Fibroblast growth factor receptor 3 (FGFR3) mutations have been implicated in urothelial tumorigenesis. FGFR3 inhibitors are being explored in clinical trials. We aimed to study the association between FGFR3 mutations and survival in urothelial carcinoma. 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. We assessed heterogeneity among study-specific HRs using I2 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. 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 (I2 = 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 (I2 = 91%). There is no association between FGFR3 mutation and EFS in NMI urothelial carcinoma, and in NMI and MI urothelial carcinoma groups. 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.