Comparison of postoperative adjuvant therapy and surgery alone in pathological N1-2 esophageal squamous cell carcinoma: A prospective multi-center randomized controlled trial.

4052 Background: Due to the lack of prospective randomized controlled clinical studies, current guidelines do not recommend postoperative adjuvant therapy, but rather observational follow-up regardless of any stage. The aim of this study was to evaluate the effect of postoperative adjuvant chemoradiotherapy and adjuvant chemotherapy on pathologic lymph node-positive (pN1-2) esophageal squamous cell carcinoma (ESCC). Methods: Patients with pathologically confirmed pN1-2 ESCC were randomly assigned to three groups: surgery alone (SA), postoperative chemotherapy (POCT), or postoperative chemoradiotherapy (POCRT). The POCT regimen included 2 to 4 cycles of docetaxel and cisplatin (75 mg/m²), while the POCRT regimen comprised 28 fractions of 5040Gy radiotherapy combined with docetaxel and cisplatin. Overall survival (OS) was the primary endpoint. Recruitment was terminated early due to the significant benefit observed in the adjuvant therapy group and difficulties in enrollment. Results: A total of 145 patients were enrolled (SA: n = 50, POCT: n = 48, POCRT: n = 47), with a median follow-up of 55 months. The overall survival rates at 3 and 5 years were 76.1% and 56.2% in the POCRT group, compared with 56.6% and 43.4% in the POCT group and 49.1% and 25.0% in the SA group, respectively. The POCRT group showed significantly improved OS and DFS compared to the SA group (OS, P = 0.003; DFS, P = 0.003). The incidence of grade 3 or higher adverse events was 39.6% in the POCT group and 44.7% in the POCRT group (P = 0.615). Conclusions: For patients with pN1-2 ESCC, postoperative therapy, especially postoperative chemoradiotherapy, significantly improved the prognosis of patients compared with surgery alone. Clinical trial information: NCT04009265 .