AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer. METHODS: Patients with T3-4 and NO-1 esophageal carcinoma from a number of institutions were non-randomly, prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m~2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m~2 and 5-fluorouracil 1000 mg/m~2 for five consecutive days), or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients’ improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-totreat patients’ outcome of survival. RESULTS: A total of 60 patients (n=30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematologicai and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI, 27.5-36.4 vs 15.2-26.1) and 3-year survival (70.0% vs 33.7%; P=0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients. CONCLUSION: For locally advanced esophageal cancer, the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress. AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer. METHODS: Patients with T3-4 and NO-1 esophageal carcinoma from a number of institutions were non-randomly, prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg / m ~ 2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg / m ~ 2 and 5-fluorouracil 1000 mg / m ~ 2 for five consecutive days), or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy Primary end-point of this study was to assess the per-protocol patients ’improvement of overall survival benefit. "Secondary end-point was designed to evaluate both the per-protocol and intent-totreat patients’ o Results: A total of 60 patients (n = 30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematologicai and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI, 27.5-36.4 vs 15.2-26.1) and 3-year survival (70.0% vs 33.7%; P = 0.003) ) was associated with favorable survival in these locally advanced patients. CONCLUSION: For locally advanced esophageal cancer, the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.