Preoperative Chemoradiotherapy versus Chemotherapy for Locally Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma: A Phase III Randomized Controlled Trial from China

Background: The prognostic superiority of preoperative chemoradiotherapy (pre-CRT) over preoperative chemotherapy (pre-CT) in patients with locally advanced gastric cancer remains controversial. Herein, we evaluated the efficacy and safety of pre-CRT relative to those of pre-CT in this cohort. Methods: This open-label, phase III, randomized controlled trial was conducted at 4 medical centers in China. Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma were randomly assigned (1:1) to receive either 3 cycles of oxaliplatin and S-1 (SOX), followed by surgery and 3 postoperative cycles of SOX (pre-CT), or 1 cycle of SOX, followed by concurrent chemoradiotherapy, a second cycle of SOX, surgery, and 3 postoperative cycles of SOX (pre-CRT). The primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included 3-year overall survival (OS), R0 resection rate, pathological complete response (pCR) rate, treatment-related toxicity, and postoperative complications. Results: Due to premature trial termination, only 204 patients were enrolled, and an efficacy analysis was conducted on 194 eligible patients. The baseline characteristics were well balanced between the 2 groups. The DFS and OS were indistinguishable between the 2 groups. The 3-year DFS rates were 53.6% in the pre-CRT group and 53.9% in the pre-CT group [hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.70 to 1.50; log-rank P = 0.913]. The 3-year OS rates were 62.8% in the pre-CRT group and 60.5% in the pre-CT group (HR, 0.97; 95% CI, 0.63 to 1.47; log-rank P = 0.874). The R0 resection rates were 81.0% and 74.5% in the pre-CRT and pre-CT groups, respectively. Additionally, the pCR rate was higher in the pre-CRT group (12.0%) than in the pre-CT group (2.1%). Treatment-related toxic effects were comparable between the 2 groups. Conclusion: This trial did not demonstrate a survival advantage for pre-CRT over pre-CT in patients with locally advanced gastric or gastroesophageal adenocarcinoma.