Abstract
Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma(ESCC)in China.However,the joint impact of prevention and treatment on the long-term overall survival(OS)of ESCC patients remains largely unknown.We consecutively recruited 13,255 ESCC patients from two Chinese centers:the Northern center,located in a high-risk area with abundant screening programs;and the Southern center,situated in a non-high-risk area with improved clinical practices.Inter-center comparison,longitudinal intra-center comparison,and a simulation analysis were conducted to investi-gate the influence of tumor downstaging and high-quality clinical treatment on OS.During a follow-up period of 12.52 years,the Northern center exhibited higher median survival than the Southern center(6.22 vs.3.15 years;HRadjusted=0.73,95％CI:0.69-0.77).Mediation analysis demonstrated that its OS advantage was largely(77.7％)attributed to earlier TNM stage(stage 0-Ⅱ:51.3％vs.24.6％).In temporal analyses,patient survival in the Southern center gradually improved(median survival during 2015-2018 vs.2009-2014:3.58 vs.2.93 years;HRadjusted=0.86,95％Cl:0.79-0.94),coinciding with the progress of treatment-related indices(completeness of TNM staging in discharge diagnosis[from 53.7％to 99.6％],adoption of minimally invasive esophagectomy[from 0.0％to 51.1％]and right thoracic esophagectomy[from 12.4％to 86.4％],etc.).Simulation analysis further demonstrated that integrating both downstaging and high-quality treatment would lead to the best survival.Tumor downstaging and high-quality clinical treatment have a joint impact on ESCC patient survival.Establishing a comprehensive strategy that inte-grates cancer prevention with optimal clinical treatment is crucial for alleviating the ESCC burden.
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