Progression‐free survival at 3 years is a reliable surrogate for 5‐year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma

BACKGROUND: Despite 3‐year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression‐free survival at 3 years (3‐year PFS) and overall survival (OS) among patients with ESCC. METHODS: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age‐ and sex‐matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. RESULTS: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3‐year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5‐year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9–17.5). Conversely, the SMR for patients who achieved 3‐year PFS was 0.9 (95% CI, 0.6–1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88–0.90). The strongest correlation was observed between 3‐year PFS and 5‐year OS in RCTs and retrospective studies. CONCLUSIONS: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3‐year PFS had excellent outcomes. Our study supports 3‐year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.