Evaluation of Event-Free Survival as a Surrogate Endpoint for Overall Survival in Muscle-Invasive Bladder Cancer Following Neoadjuvant Treatment: A Systematic Review and Meta-Analysis.

INTRODUCTION: Event-free survival (EFS), a common endpoint in neoadjuvant/perioperative oncology trials, allows for accelerated treatment evaluation while awaiting results of overall survival (OS). However, the surrogacy of EFS for OS in muscle-invasive bladder cancer (MIBC) has yet to be established. This meta-analysis evaluated EFS as a surrogate endpoint for OS in neoadjuvant-treated MIBC.

METHODS: A systematic literature review identified neoadjuvant or perioperative clinical trials for MIBC reporting both EFS and OS. Treatment effect association was evaluated by assessing the association of the hazard ratio (HR) of EFS with that of OS. Survival outcome associations were evaluated by assessing the associations of survival rates and median survival times between EFS and OS, respectively. These associations were meta-analyzed using weighted linear regression. The strength of association was quantified using coefficient of determination (R2).

RESULTS: Seven eligible trials were identified for the analysis of treatment effect association and 17 trials were included in the analyses of survival outcome associations. Strong association was observed between EFS and OS at treatment effect level (R2 = 0.80 [95% confidence interval (CI): 0.38-0.99]). Consistently, significant survival outcome associations were observed between 3-year EFS and 5-year OS (R2 = 0.80 [95% CI: 0.28-0.93]) and between median EFS time and median OS time (R2 = 0.97 [95% CI: 0.45-1.00]).

CONCLUSIONS: EFS is strongly associated with OS in respect to treatment effects and survival outcome measures in clinical trials for MIBC following neoadjuvant treatment. EFS can be considered as a surrogate endpoint for OS when evaluating neoadjuvant treatments for MIBC.