A Randomized Open-Label, Noninferiority, Phase 3, Multicenter, Controlled Trial to Compare Laparoscopic Surgery With Open Surgery for Symptomatic, Noncurable Stage IV Colorectal Cancer (JCOG1107)

Objective: To confirm noninferiority of laparoscopic (LAP) to open surgery (OP) for progression-free survival (PFS) of patients with non-curable stage IV colorectal cancer (CRC). Background: Benefits of LAP versus OP are suggested, but long-term survival following LAP for symptomatic, noncurable CRC remains unclear. Methods: In this open-label, multicenter, randomized controlled trial, only accredited surgeons from 42 Japanese institutions participated. Eligibility criteria included pathologically proven adenocarcinoma or adenosquamous carcinoma; primary tumor anywhere in the colon causing bowel stenosis and/or bleeding; and at least 1 to 3 noncurable factors. Patients received mFOLFOX6+bevacizumab or CapeOX+bevacizumab postoperatively and were randomly assigned 1:1 to the OP or LAP group. The primary endpoint was PFS, with noninferiority margin for the hazard ratio (HR) set at 1.38. Results: Between January 2013 and January 2021, 195 patients were randomized (OP, n = 95, LAP, n = 100). Ninety-two patients received OP and 98 LAP, with 82 OP and 86 LAP patients receiving postoperative chemotherapy. Median PFS was 9.7 months (95% CI = 8.7–11.3) for OP and 10.4 months (9.1–12.4) for LAP. Noninferiority of LAP was confirmed [HR = 1.02; 91.4% CI = 0.79–1.32 (<1.38), P for noninferiority = 0.021]. Median overall survival was 23.9 months (95% CI = 18.6–29.4) for OP and 25.4 months (19.4–29.0) for LAP (HR = 0.99; 95% CI, 0.72–1.36). In-hospital mortality was 1.1% (OP) and 0% (LAP). Postoperative complications (Grade 2–4) included ileus (OP = 12.0%; LAP = 5.1%), wound infection (OP = 2.2%; LAP = 2.0%), and anastomotic leakage (OP = 0%; LAP = 2.0%). Conclusions: LAP appears to be an acceptable standard treatment for symptomatic, noncurable stage IV CRC. Trial registration: UMIN-CTR, number UMIN000009715.