Prognostic and Predictive Value of Fibroblast Growth Factor Receptor Alterations in High-grade Non-muscle-invasive Bladder Cancer Treated with and Without Bacillus Calmette-Guerin Immunotherapy

Background: Limited data are available on the prognostic and predictive value of fibroblast growth factor receptor alterations (FGFRa) relative to clinical outcomes in patients with non-muscle-invasive bladder cancer (NMIBC).Objective: To determine whether FGFRa may be clinically useful in stratifying for treatment response in a real-world cohort of patients with pT1 NMIBC treated and untreated with bacillus Calmette-Guerin (BCG) instillation therapy.Design, setting, and participants: A pooled dataset of matched clinical and genomic data (1992-2015) for pT1 NMIBC patients was assessed by the Bladder Cancer Research Initiative for Drug Targets in Germany consortium.Outcome measurements and statistical analysis: Key efficacy outcomes were recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS), which were estimated by Kaplan-Meier analysis, with hazard ratios calculated using a multivariate Cox proportional-hazard model.Results and limitations: In this retrospective study of 263 patients with high-grade NMIBC, at a median follow-up of 63 mo, 32% showed recurrence and 15% progressed to muscle-invasive bladder cancer. FGFRa were found in 43% of patients, including 39% mutations and 5.7% fusions. FGFRa were associated with lower rates of concomitant carcinoma in situ. Among patients with or without FGFRa, there was no significant dif-ference in PFS, RFS, and DSS in those who were BCG treated or BCG naive, or in the over-all population. Limitations include the retrospective design from a single-center setting. Conclusions: In patients with high-risk NMIBC, FGFRa were frequently observed. Patients with FGFRa who often exhibit recurrence/relapse after BCG treatment have a high unmet need. Patient summary: Our retrospective study suggests that fibroblast growth factor recep-tor alterations (FGFRa) occur frequently in non-muscle-invasive bladder cancer (NMIBC).Outcomes were similar with or without FGFRa in patients with NMIBC, both overall and for standard bacillus Calmette-Guerin (BCG) treatment. (c) 2022 The Authors.Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).