Evaluation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Localized Pancreatic Cancer: Trans-Atlantic Pancreatic Surgery Consortium Study

Abstract Background Overall survival (OS) is considered the reference-standard endpoint for assessing treatment efficacy in oncology but requires prolonged follow-up evaluation. This study assessed progression-free survival (PFS) as a surrogate endpoint for OS in patients with localized pancreatic ductal adenocarcinoma (PDAC). Methods This retrospective international multicenter study included patients with a diagnosis of localized PDAC who were treated with at least one cycle of (m)FOLFIRINOX (2012–2022). Surrogacy between PFS and OS was assessed at the individual level using the Kendall rank correlation coefficient (Kendall’s τ ), with a τ of 0.8 considered the threshold for good surrogacy. Results This study analyzed 1783 patients with a median age of 64.0 years, and 43.4% underwent surgical resection. The median OS was 22.2 months, and the median PFS was 12.8 months. Kendall’s τ was 0.647 (95% confidence interval [CI], 0.626–0.668) overall and was higher for patients with lower baseline tumor burdens (primarily resectable [0.730], borderline resectable [0.640], locally advanced [0.601]), and more favorable pathologic responses (from 0.822 for ypT0 to 0.535 for ypT3–4, and from 0.755 for ypN0 to 0.541 for ypN2). The median post-progression survival was 6.7 months (interquartile range, 3.3–13.4 months). Conclusions Individual-level surrogacy between PFS and OS did not meet the prespecified threshold for good surrogacy due to considerable interpatient variability in post-progression survival, supporting the continued use of OS as the gold-standard efficacy endpoint in clinical trials. However, surrogacy was stronger among patients with lower pretreatment tumor burdens and more favorable pathologic responses, potentially facilitating perioperative treatment development through shorter follow-up periods in pancreatic cancer trials.