Surrogacy of Intermediate Clinical Endpoints for Overall Survival in Patients With Localized Muscle-Invasive Bladder Cancer - PubMed
5 hours ago
- #Clinical Trials
- #Surrogate Endpoints
- #Bladder Cancer
- The study evaluated intermediate clinical endpoints (ICEs) as potential surrogates for overall survival (OS) in localized muscle-invasive bladder cancer (MIBC) patients.
- Analysis included 4,828 patients across 29 European centers, using inverse probability of treatment weighting to compare neoadjuvant chemotherapy plus radical cystectomy versus cystectomy alone.
- Pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) were assessed using adapted Prentice criteria, proportion of treatment effect explained, and a meta-analytic framework.
- Results showed pCR and pOR had uncertain surrogacy (low R² values), while DFS demonstrated strong surrogacy with a pseudo-trial-level R² of 0.83 and a surrogate threshold effect of 0.82.
- The study concluded that DFS is a valid surrogate endpoint for OS in randomized controlled trials for localized MIBC when a risk reduction of ≥18% is expected.