Progression-free survival as a surrogate of overall survival in metastatic or recurrent endometrial cancer: an EORTC gynecologic cancer group study

Objective: The value of progression-free survival as a surrogate marker for overall survival remains a matter of debate. Herein, we evaluated the validity of progression-free survival as a surrogate endpoint for overall survival in trials of recurrent or metastatic endometrial cancer. Methods: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Standardized treatment effects (z-scores) for progression-free-survival and overall survival were derived from reported HRs. Pearson's correlation coefficient (r) and surrogate threshold effect (STE) were calculated to assess surrogacy according to German Institute for Quality and Efficiency in Health Care guidelines. Sub-group analyses were performed by treatment modality, line of therapy, and prior radiotherapy exposure. Results: Sixteen randomized trials encompassing 25 treatment comparisons and 10,381 patients with recurrent or metastatic endometrial cancer were included. A strong correlation was observed between zPFS and zOS across all studies (r = 0.82, 95% CI 0.63 to 0.92, p < .001). The STE was 3.07, indicating that moderate-to-large progression-free-survival benefits are required to predict overall-survival improvement. Correlation was strongest among chemoimmunotherapy trials (r = 0.87, 95% CI 0.34 to 0.98, p = .011, STE = 3.34), while chemotherapy-alone trials showed a weak and non-significant association (r = 0.42, 95% CI −0.49 to 0.89, p = .35, STE = 3.64). Surrogacy appeared stronger in post-first-line trials and in studies with limited prior radiotherapy exposure. Conclusions: Progression-free survival shows a strong but context-dependent correlation with overall survival among endometrial cancer trials. While it may serve as a valid surrogate marker, particularly in chemoimmunotherapy, its reliability varies by treatment context. These findings support the selective use of progression-free survival as a surrogate in endometrial cancer and underscore the importance of tailored endpoint strategies in oncology trial design.