ArticleEsophagus : official journal of the Japan Esophageal Society2026
Heterogeneity of adjuvant therapy effectiveness across post-neoadjuvant pathologic strata in esophageal squamous cell carcinoma: a retrospective cohort study.
Article in Esophagus : official journal of the Japan Esophageal Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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- Erratum issued
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Abstract
backgroundAdjuvant therapy after neoadjuvant treatment and R0 esophagectomy for esophageal squamous cell carcinoma (ESCC) remains controversial, and benefit may vary by post-neoadjuvant pathology. We evaluated heterogeneity of adjuvant benefit across prespecified pathologic strata and quantified absolute survival gains.
methodsIn this two-center retrospective cohort (January 2018-May 2023), patients with ESCC who underwent neoadjuvant therapy followed by R0 resection were classified as pCR (ypT0N0), ypT+N0, or ypT0-4N+. The exposure was early postoperative adjuvant therapy initiated within 8 weeks after surgery. To reduce immortal-time bias, we used an 8-week landmark design with follow-up from the landmark. Confounding was addressed using stabilized inverse probability of treatment weighting (sIPTW) based on preoperative covariates, center, and surgical approach. Outcomes were overall survival (OS) and disease-free survival (DFS) using weighted Cox models with robust standard errors; absolute differences in survival probability (ΔS) were derived from weighted Kaplan-Meier curves.
resultsAmong 781 patients (pCR 142, ypT+N0 317, ypT0-4N+ 322), survival for pCR and ypT+N0 largely overlapped, whereas ypT0-4N+ had consistently worse outcomes. In the overall cohort, adjuvant therapy was not associated with improved OS (HR 0.99, 95% CI 0.75-1.31; P = 0.946) or DFS (HR 1.15, 95% CI 0.89-1.48; P = 0.283). Benefit was concentrated in ypT0-4N+ (OS HR 0.48, 95% CI 0.33-0.72; P < 0.001; DFS HR 0.64, 95% CI 0.46-0.90; P = 0.011), with ΔS +13.2 percentage points for DFS at 1 year and +21.0 percentage points for OS at 3 years. No clear benefit was observed in pCR or ypT+N0.
conclusionsAfter neoadjuvant therapy and R0 resection for ESCC, post-neoadjuvant nodal status strongly stratified prognosis, with similar survival for pCR and ypT+N0. Adjuvant benefit is heterogeneous and concentrated in ypN-positive disease, supporting a pathology-informed, risk-adapted postoperative strategy targeting ypT0-4N+.
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