Three-Year Follow-Up of the Randomized Trial Comparing Open Versus Laparoscopic Surgery for Primary Tumor Resection in Patients With Non-Curable Stage IV Colon Cancer (JCOG1107)

BACKGROUND: JCOG1107 (UMIN-CTR, number UMIN000009715) was a non-inferiority phase III trial comparing laparoscopic and open surgery for symptomatic, non-curable stage IV colon cancer. The primary analysis confirmed the non-inferiority of laparoscopic surgery in terms of progression-free survival. OBJECTIVE: To compare long-term outcomes of laparoscopic and open surgery for stage IV colon cancer. DESIGN: Multicenter, open-label, randomized, controlled phase III trial. SETTING: Forty-two Japanese institutions. PATIENTS: Participants were considered eligible if they had pathologically confirmed adenocarcinoma or adenosquamous carcinoma with a primary tumor between the cecum and rectosigmoid, presenting with stenosis and/or bleeding, and one to three non-curable factors. The required sample size was 194 to ensure 70% power, a one-sided alpha of 5%, and a non-inferiority hazard ratio margin of 1.38. INTERVENTIONS: Patients were randomized to receive either open or laparoscopic primary tumor resection, followed by modified FOLFOX6 plus bevacizumab or capecitabine plus oxaliplatin with bevacizumab. MAIN OUTCOME MEASURES: The primary endpoint was progression-free survival. RESULTS: A total of 195 patients were randomized, including 95 open and 100 laparoscopic surgeries. Postoperative chemotherapy was given to 82 and 86 patients, respectively. The median follow-up period for all randomized patients was 24.4 months. Grade ≥3 late complications occurred in one open (1.1%) and two laparoscopic (2.0%) patients. Three-year progression-free survival was 5.3% (95% confidence interval: 2.0-11.0) for open surgery and 3.0% (0.8-7.8) for laparoscopic surgery (hazard ratio: 1.028; 95% confidence interval: 0.772-1.370; p for non-inferiority = 0.02). The three-year overall survival was 31.5% (22.5-41.0) and 28.5% (20.0-37.6) (hazard ratio: 1.048; 95% confidence interval: 0.780-1.410), respectively. LIMITATIONS: Chemotherapy was administered without knowledge of microsatellite instability or RAS/BRAF mutation status. CONCLUSION: Laparoscopic surgery is non-inferior to open surgery for non-curable stage IV colon cancer and should be considered an acceptable surgical option. See Video Abstract.