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.