Neoadjuvant versus adjuvant chemoradiotherapy for resectable cT3-4a esophageal squamous cell carcinoma: A matched cohort analysis

Abstract

Background: The optimal management of locally advanced resectable esophageal squamous cell carcinoma (ESCC), particularly for cT3-4a disease, remains debated. This study aimed to compare the survival outcomes and toxicity profiles of neoadjuvant chemoradiotherapy (NCRT) and adjuvant chemoradiotherapy (ACRT) in this patient population.

Methods: We retrospectively analyzed 223 patients with resectable cT3-4a ESCC who underwent radical surgery combined with NCRT or ACRT. Propensity score matching (PSM) was used to generate 59 balanced pairs for comparative analysis.

Results: After matching, the NCRT group demonstrated significantly improved overall survival (OS) compared with the ACRT group, with a median OS of 62 versus 46 months and 5-year OS rates of 66.6% versus 47.5%, respectively (p = 0.023). Despite the longer median progression-free survival (PFS) observed in the NCRT group (53 vs. 42 months), the difference in the 5-year PFS rate was not statistically significant (56.7% vs. 44.4%; p = 0.113). Furthermore, the two groups exhibited similar profiles of treatment-related adverse events (all p > 0.05). Multivariable analysis identified treatment strategy, body mass index (BMI), and clinical nodal (cN) status as independent predictors of OS (all p < 0.01). A novel prognostic score (PS) integrating BMI and cN status effectively stratified patients into distinct risk categories, with higher scores predicting poorer prognosis but not in the neoadjuvant subgroup.

Conclusions: For patients with resectable cT3-4a ESCC, NCRT provides superior OS compared to ACRT, with similar PFS and toxicity. These findings support the prioritization of NCRT for this disease stage; however, larger randomized trials are warranted to optimize patient selection.

Keywords

Adjuvant chemoradiotherapy / Esophageal squamous cell carcinoma / Neoadjuvant chemoradiotherapy / Prognosis / Propensity score matching

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2026 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.