Disease‐free survival as a surrogate outcome for localized kidney cancer—A systematic review and meta‐analysis
Constanza Martinez, David Chen, Russell Leong, Nicholas Lum, Karren Xiao, Laith Almasri, Christian K. Kollmannsberger, Srinivas RamanAbstract
Background
Disease‐free survival (DFS) is commonly used as a primary end point in trials for localized renal cell carcinoma ( R CC), 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.
Methods
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.
Results
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.
Conclusions
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.