Phase 3 trial of neoadjuvant chemoradiotherapy with surgery versus surgery with adjuvant therapy for esophageal squamous cell carcinoma

The optimal treatment strategy for resectable locally advanced esophageal squamous cell carcinoma (LA ESCC) is not clear. A phase 3 trial at Sichuan Cancer Center (Chengdu, China) compared neoadjuvant chemoradiotherapy (nCRT) followed by surgery versus frontline surgery followed by adjuvant therapy (AT) for LA ESCC. In this trial of 254 patients, the 5-year disease-free survival rate was 53.1% in the nCRT group and 56.5% in the AT group, and the 5-year overall survival rate was 59.2% in the nCRT group and 59.6% in the AT group, showing no significant differences between the groups. Subgroup analyses showed that patients achieving pCR in the nCRT group had significantly improved survival outcomes, with a 5-year OS rate of 76.5% compared with 52.1% for non-pCR patients (HR 0.31; p=0.01). The authors conclude that surgery followed by adjuvant therapy remains a reasonable option for resectable disease, emphasizing the need to identify patients most likely to benefit from nCRT.