Question: Does chemoradiotherapy after surgery increase the survival of gastric cancer patients having an intended curative resection? Design: Randomised controlled trial in nine US cancer centres. Patients: A total of 556 patients with an adenocarcinoma of the stomach (mostly distal) or gastro-oesophageal junction (20%), of which two thirds had T3 or T4 tumours and 85% had nodal metastases in resected specimens. Intervention: Chemoradiotherapy started approximately one month after surgery. Chemotherapy, given before and after radiotherapy, consisted of fluorouracil and leucovorin, and radiotherapy of 4500 cGy at 180 cGy per day for five days per week for five weeks, given to the tumour bed and resection margins and to the regional nodes. Outcome measures: The primary outcome was survival time and the secondary outcome was relapse free survival. Results: Of 556 patients, 275 were randomised to surgery alone and 281 to surgery plus chemotherapy, of whom 181 (64%) completed treatment as planned; 8% declined treatment, 17% stopped because of toxicity, and 10% discontinued treatment for other reasons, including disease progression. Most patients (54%) had a partial resection of affected nodes (DO), 36% had full resection of affected nodes (D 1), and only 10% had a D2 resection. Significant (grade 3) toxic effects were frequent and were haematological in 148 (54%) and gastrointestinal in 89 (33%). Other toxicity occurred in less than 10% but three patients died of toxic effects attributed to chemoradiotherapy. After a median follow up of five years, median survival in the surgery only group was 27 months compared with 36 months in the chemoradiotherapy group (hazard ratio 1.35, 95% confidence interval (Cl) 1.1-1.7; p=0.005). Median duration of relapse free survival was 19 months in the surgery only group compared with 30 months in the chemoradiotherapy group (hazard ratio for relapse 1.52, 95% Cl 1.2-1.9; p<0.001). Relapses were reported in 43% of the chemoradiotherapy group compared with 64% of the surgery only group. Conclusion: Chemoradiotherapy given after intended curative surgery for gastric cancer prolonged survival by approximately one third.
