An RMST-based analysis of systemic therapy in muscle-invasive bladder cancer

Recent Phase III trials using immunotherapy agents in perioperative setting for muscle-invasive bladder cancer (MIBC) have reshaped treatment paradigms. Traditional hazard ratios, while statistically robust, may mask modest absolute survival gains, complicating informed decision-making for clinicians and patients alike. This study aims to utilize restricted mean survival time (RMST) analysis to provide more intuitive interpretations of survival benefits and facilitate development of a framework for comparing efficacy, toxicity, and costs across three pivotal trials.

Overall survival (OS), disease free survival (DFS) and adverse effects (AE) data were extracted from recently published Phase III MIBC trials reporting results by HR: NIAGARA (perioperative durvalumab), CheckMate-274 (adjuvant nivolumab) and AMBASSADOR (adjuvant pembrolizumab). Using reconstructed individual patient data, RMST was calculated at a 42-month truncation. Costs were sourced from U.S. Medicare prices and calculated using each study's median treatment duration.

DFS-RMST differences at 42 months were: 3.39 months (95% CI: 1.4-5.39) for NIAGARA, 4.05 months (95% CI: 1.33-6.78) for CheckMate-274, and 3.97 months (95% CI: 1.3-6.65) for AMBASSADOR. OS-RMST differences were: 1.84 months (95% CI: 0.37-3.37) for NIAGARA, 2.56 months (95% CI: 0.54-4.58) for CheckMate-274, and 0.95 months (95% CI: -1.21 to 3.15) for AMBASSADOR. Cost per month of survival gained ranged from $43,460 to $49,832 for DFS and $52,387 to $207,374 for OS across trials.

Our RMST-based analysis highlights the minimal real-world survival benefits and provides more intuitive and clinically relevant interpretations than traditional hazard ratios. Our visualization framework offers an intuitive approach to assist clinicians and patients in making informed decisions.