Adjuvant Chemoradiotherapy or Chemotherapy After D2 Gastrectomy in Gastric Cancer: A Randomized Clinical Trial.

Abstract

Despite advances in D2 gastrectomy (ie, gastrectomy with D2 lymphadenectomy) and adjuvant chemotherapy, the value of adding postoperative radiotherapy (RT) to adjuvant chemotherapy after D2 gastrectomy remains a topic of ongoing debate. To assess whether the addition of RT to the S-1 plus oxaliplatin (SOX) chemotherapy regimen increases disease-free survival (DFS) in patients with T4 or node-positive gastric cancer after D2 gastrectomy. This open-label, phase 3 randomized clinical trial was conducted between December 1, 2012, and August 30, 2022, at 5 large tertiary hospitals in China. Eligible patients were aged 18 to 70 years with gastric adenocarcinoma who underwent R0 resection with D2 lymphadenectomy, had pathologic stage T4 or node-positive disease, and had no evidence of metastasis (M0). Intention-to-treat statistical analyses were conducted from January 14 to March 31, 2025. Participants were assigned 1:1 to receive concurrent chemoradiotherapy (SOX RT) or chemotherapy alone (SOX). The SOX RT group received 1 cycle of induction SOX, followed by RT (50.4 Gy in 28 fractions) with concurrent S-1 (50 mg twice daily), and then 3 cycles of SOX. The SOX group received 6 cycles of SOX (S-1 30-40 mg/m2 twice daily on days 1-14; oxaliplatin 130 mg/m2 on day 1, every 3 weeks). The primary end point was 3-year DFS. Secondary end points included overall survival (OS) and adverse events. A total of 620 patients were randomly assigned to the SOX group (n = 311) or SOX RT group (n = 309). Patients had a median (IQR) age of 55 (47-62) years and included 401 males (64.7%). Overall, 274 patients (44.2%) had T4 disease, and 590 (95.2%) had node-positive disease. In the primary analysis for the prespecified 3-year DFS end point, there was no evidence of a between-group difference in DFS (SOX RT vs SOX: HR, 0.98; 95% CI, 0.73-1.33). Similarly, there was no evidence of a between-group difference in OS (HR, 0.86; 95% CI, 0.60-1.23). The Kaplan-Meier-estimated 3-year DFS rates were 70.5% in the SOX RT group and 69.3% in the SOX group (log-rank P = .93), and the corresponding 3-year OS rates were 80.8% and 78.4%, respectively (log-rank P = .41). At 5 years, the DFS rates were 60.0% and 57.3% (log-rank P = .76) and the corresponding OS rates were 73.7% and 71.4% (log-rank P = .55) in the SOX RT and SOX groups, respectively. Treatment-related adverse events were similar between groups. In this randomized clinical trial of patients with T4 or node-positive gastric cancer who underwent D2 gastrectomy, SOX RT did not significantly improve DFS or OS. Accordingly, among patients with D2-resected gastric cancer, the findings do not support routine addition of adjuvant chemoradiotherapy to chemotherapy. Chinese Clinical Trial Registry Identifier: ChiCTR-TRC-12002919.