Prognostic Impact of Circumferential Resection Margin in Minimally Invasive Surgery for Locally Advanced Rectal Cancer: A Multicenter Prospective Study.

AIM: Circumferential resection margin (CRM) status is a well-established prognostic factor in rectal cancer surgery; however, its long-term oncological relevance has not been prospectively validated in Japan, where upfront surgery has long been widely used. This study assessed the prognostic impact of CRM in patients with locally advanced rectal cancer treated with minimally invasive surgery. METHODS: The PRODUCT trial was a multicenter, prospective, observational study conducted at 18 institutions in Japan. Patients aged ≥ 20 years with clinical stage II or III rectal adenocarcinoma located within 12 cm from the anal verge and scheduled for laparoscopic or robotic surgery were enrolled. CRM positivity was defined as a margin of ≤ 1 mm. Long-term outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: Among 303 eligible patients, CRM positivity was observed in 26 (8.6%). The 3-year recurrence-free survival (RFS) rate was significantly lower in the CRM-positive group than in the CRM-negative group (61.5% vs. 82.3%; log-rank p = 0.003). CRM positivity was independently associated with worse RFS (hazard ratio, 2.35; 95% confidence interval, 1.17-4.71; p = 0.016). In patients with pT3-T4 tumors, recurrence rates were significantly higher in CRM-positive cases than in CRM-negative cases (47.6% vs. 21.2%; p = 0.013). CRM status was not significantly associated with overall survival or cumulative incidence of local recurrence (p = 0.057 and p = 0.706, respectively). CONCLUSIONS: CRM positivity is an adverse prognostic factor in Japanese patients with locally advanced rectal cancer undergoing MIS, underscoring the clinical importance of standardized CRM assessment. TRIAL REGISTRATION: Clinical Trials Registry, Identification Number: UMIN00034365.