A phase III clinical trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus

Abstract

Background: Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of locally advanced ESCC. Nevertheless, the results of different studies were inconsistent. We are to carry out a phased III clinical trial to investigate the effect of this multidisciplinary therapy for the overall survival of patients with locally advanced ESCC. Methods: According to Sixth Edition AJCC Cancer Staging, patients with IIB‐III staged squamous cell carcinoma of the thoracic esophagus are randomly allocated to either preoperative chemoradiotherapy followed by surgery (arm A), or surgery alone (arm B). The intended number of randomized patients will be 430, 215 per arm. In the arm A, Chemotherapy and radiotherapy are performed concurrently. Patients received two cycles of vinorelbine and cisplatin. Vinorelbine at 25 mg/m2 per day is administered in bolus infusion on d1, d8, d22 and d29. Cisplatin at 75 mg/m2 is administered by intravenously infusion on d1 and d22 (or 25 mg/m2 days 1 to 4 and 22 to 25). A total radiotherapy dose of 40 Gy is delivered in 20 daily fractions of 2.0 Gy each (given 5 d/wk for 4 weeks). McKeown esophagectomy or Ivor Lewis esophagectomy will be performed 4‐8 weeks after chemoradiotherapy. Two‐field lymphadenectomy with total mediastinal lymph node dissection is performed during sugery. Primary outcomes are 3 and 5 years overall survival. Results: From July 2007 to December 2014, 451 eligible patients were randomly assigned in eight cooperative cancer centers (224 cases in arm A, and 227 cases in arm B). The median follow‐up for surviving patients was 30.6 months. In arm A, 185 cases continued to undergo surgery after chemoradiotherapy. The rate of R0 resection was 98.4% (182/185) in arm Aversus 91.2% (207/227) in arm B (P = 0.002). A pathological complete response was achieved in 80 of 185 patients (43.2%) who underwent resection in the arm A. The overall survivals at 3 years in arm A was significantly higher than arm B (69.6% vs 62.4%; HR 0.71 [95% CI 0.52‐0.98]; log‐rank P = 0.035). Conclusions: Neoadjuvant chemoradiotherapy plus surgery improved survival among patients with locally advanced esophageal squamous cell carcinoma.