Disease-free survival as a surrogate outcome for localized kidney cancer-A systematic review and meta-analysis

Disease-free survival (DFS) is commonly used as a primary end point in trials for localized renal cell carcinoma (RCC), although its validity as a surrogate for overall survival (OS) remains uncertain. The objective of this study was to evaluate whether DFS is a reliable surrogate end point for OS in this setting.

The authors conducted a systematic review and trial-level meta-analysis of randomized controlled trials assessing systemic or perioperative therapies in patients with localized RCC. Databases were searched from inception to June 10, 2025. Trial-level surrogacy between DFS and OS was assessed using weighted least-squares meta-regression of log-transformed hazard ratios (HRs), and the surrogate threshold effect was estimated.

In total, 25 randomized controlled trials were analyzed; 13 trials, analyzed as 15 study-level units comprising 9594 patients, reported HRs for both OS and DFS. DFS demonstrated a strong correlation with OS (weighted Pearson correlation coefficient, 0.75; 95% confidence level, 0.55-0.91; corresponding coefficient of determination, 0.57). The surrogate threshold effect analysis identified a DFS HR <0.914 as predictive of OS benefit. Funnel plots showed no clear asymmetry, and Egger tests did not indicate significant publication bias.

DFS demonstrated a strong association with OS and may serve as a valid trial-level surrogate end point patients with in localized RCC. A DFS HR <0.914 was more likely to predict an OS benefit. These findings support the use of DFS as a primary end point in localized RCC trials, whereas continued long-term follow-up and future patient-level validation remain important.