JCOG1107 was a multicenter, open‑label, randomized phase III noninferiority trial that compared laparoscopic surgery with open surgery for resection of the primary tumor in patients with symptomatic, noncurable stage IV colon cancer. The primary aim was to determine whether laparoscopic resection was noninferior to open resection with respect to progression‑free survival (PFS). The primary analysis previously demonstrated noninferiority for PFS; this report provides three‑year follow‑up outcomes.
The study was conducted across 42 Japanese institutions as an open‑label, randomized controlled phase III trial. The trial was registered (University Hospital Medical Information Network Clinical Trials Registry, No. UMIN000009715). The planned sample size was 194 patients, calculated to provide 70% power with a one‑sided alpha of 5% and a pre‑specified noninferiority hazard ratio (HR) margin of 1.38 for the primary end point.
Eligible participants had pathologically confirmed adenocarcinoma or adenosquamous carcinoma located between the cecum and rectosigmoid. Patients presented with stenosis and/or bleeding from the primary tumor and had 1 to 3 noncurable metastatic factors. A total of 195 patients were randomized: 95 to the open surgery arm and 100 to the laparoscopic surgery arm.
Patients were randomly assigned to undergo either open primary tumor resection or laparoscopic primary tumor resection. Surgery was followed by postoperative systemic therapy per protocol. The study was open‑label; treating clinicians and patients were aware of the assigned surgical approach.
Postoperative chemotherapy was delivered to most patients: 82 patients in the open group and 86 patients in the laparoscopic group received systemic therapy. Regimens used included modified oxaliplatin, 5‑fluorouracil (5‑FU), and folinic acid plus bevacizumab, or capecitabine plus oxaliplatin with bevacizumab. The report notes that chemotherapy administration occurred without knowledge of microsatellite instability or RAS/BRAF mutation status.
The primary end point of the trial was progression‑free survival. Secondary outcomes reported in the three‑year follow‑up included overall survival (OS) and postoperative complications, including late adverse events graded by severity.
The median follow‑up period for all randomized patients was 24.4 months. Late postoperative complications of grade 3 or higher were uncommon: one patient (1.1%) in the open surgery group and two patients (2.0%) in the laparoscopic group experienced grade ≥3 late complications.
Three‑year progression‑free survival rates were reported as follows: 5.3% (95% CI, 2.0–11.0) for the open surgery group and 3.0% (95% CI, 0.8–7.8) for the laparoscopic group. The hazard ratio for PFS comparing laparoscopic with open surgery was 1.028 (95% CI, 0.772–1.370).
Three‑year overall survival rates were 31.5% (95% CI, 22.5–41.0) after open surgery and 28.5% (95% CI, 20.0–37.6) after laparoscopic surgery. The HR for OS was 1.048 (95% CI, 0.780–1.410).
The trial prespecified a noninferiority HR margin of 1.38 for PFS. With the observed HR for PFS of 1.028 (95% CI, 0.772–1.370), the noninferiority test yielded a p value for noninferiority of 0.02, supporting the conclusion that laparoscopic surgery is noninferior to open surgery for the primary end point of PFS in this population.
The authors noted that chemotherapy was administered without molecular profiling information, specifically microsatellite instability status and RAS/BRAF mutation status. The open‑label design and the fact that follow‑up median duration was 24.4 months are additional contextual features readers should consider when interpreting long‑term outcomes.
At three years of follow‑up, laparoscopic resection of the primary tumor in symptomatic, noncurable stage IV colon cancer demonstrated noninferiority to open resection with respect to progression‑free survival. Overall survival at three years was similar between groups. Late severe postoperative complications were rare in both arms. Based on these results, laparoscopic surgery should be considered an acceptable surgical option for this patient population. The report highlights that systemic therapy in the trial was given without knowledge of certain molecular markers, a limitation to be considered in clinical decision making.