Time-dependent prognostic impact of circumferential resection margin in T3 thoracic esophageal squamous cell carcinoma

Abstract

Summary Esophageal cancer presents a clinical challenge due to its high incidence and unfavorable prognosis. The prognostic role of the circumferential resection margin (CRM) remains highly controversial, potentially due to its temporal dynamics coupled with variability in follow-up durations across studies. We aimed to explore the time-dependent prognostic significance of CRM in T3 esophageal squamous cell carcinomas (ESCCs). We systematically reviewed literature from 1990 to 2023 to determine how follow-up duration influences the prognostic role of CRM in esophageal cancer. Concurrently, we performed a retrospective examination of 354 patients who underwent treatment at the National Cancer Center between 2015 and 2018. Integrating a time interaction term in the Cox regression analyses enabled us to not only identify independent risk factors affecting overall survival (OS) but also to specifically scrutinize the potential temporal variations in CRM’s prognostic impact. Our literature review suggested that CRM’s influence on prognosis diminishes with longer follow-up durations for both classifications, namely the Royal College of Pathologists (RCP) (β = −0.003, P < 0.001) and the College of American Pathologists (CAP) (β = −0.007, P < 0.001). Time-dependent multivariate Cox regression analysis emphasized the evolving nature of CRM’s prognostic effect, and the inclusion of the time interaction term enhanced model accuracy. In conclusion, CRM is an independent prognostic factor for T3 thoracic ESCC patients. Its influence appears to decrease over extended follow-up periods, shedding light on the heterogeneity seen in previous studies. With the time interaction term, CRM becomes a more precise post-operative prognostic indicator for esophageal cancer.