Efficacy comparison of neoadjuvant chemotherapy, chemoradiotherapy, and chemoimmunotherapy in resectable esophageal squamous cell carcinoma: short- and long-term outcomes from a propensity score-matched analysis

Abstract

This study consecutively enrolled patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) treated at Fujian Medical University Union Hospital and Gaozhou People's Hospital between January 1, 2,019, and January 1, 2022. All patients received neoadjuvant therapy followed by minimally invasive McKeown esophagectomy and were categorized according to treatment modality: neoadjuvant chemotherapy (nCT), chemoradiotherapy (nCRT), or chemoimmunotherapy (nICT). Propensity score matching yielded 78 patients per group. The primary endpoints were 3-year overall survival (OS), recurrence-free survival (RFS), and recurrence patterns. One-year RFS was significantly lower in the nCT group than in the nCRT and nICT groups ( p  = 0.020), whereas 2-year OS was significantly higher in the nICT group ( p  = 0.018). However, no statistically significant differences were observed in 3-year OS or RFS. Recurrence occurred significantly earlier in the nCT group than in the nICT group ( p  < 0.05), with no statistically significant differences in the other pairwise comparisons. In this retrospective matched-cohort study, nICT did not significantly improve 3-year OS or RFS compared with nCRT, although recurrence appeared to occur later in the nICT group. These findings should be interpreted as hypothesis-generating, as potential long-term immunotherapy effects and radiotherapy-related modulation of long-term benefit could not be assessed. The lower survival observed in the nCT group suggests that chemotherapy alone may be insufficient for ESCC. Prospective trials are warranted to confirm long-term benefits and identify patients most likely to benefit from nICT.