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

Sidra Khalid; Bassam Mohammed Basulaiman; Jeffrey Emack; Christopher M Booth; Ignacio Duran; Andrew G Robinson; David Berman; Martin Smoragiewicz; Eitan Amir; Francisco E Vera-Badillo

doi:10.1016/j.euros.2020.08.008

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

Eur Urol Open Sci. 2020 Oct 13:21:61-68. doi: 10.1016/j.euros.2020.08.008. eCollection 2020 Oct.

Authors

Affiliations

¹ Department of Oncology, Queen's University, Kingston, ON, Canada.
² Division of Medical Oncology, University of Ottawa, Ottawa, ON, Canada.
³ Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada.
⁴ Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
⁵ Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
⁶ Division of Medical Oncology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
⁷ Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Abstract

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.

Keywords: Fibroblast growth factor receptor 3 mutation; Muscle invasive; Non-muscle invasive; Progression-free survival; Recurrence-free survival; Urothelial carcinoma.