Anastomotic Leak Following Colon Cancer Resection: An Independent Predictor of Non‐Oncologic Mortality and Morbidity

Background Anastomotic leak (AL) is a serious complication following colon cancer resection, but its long‐term impact on survival and recurrence remains uncertain. Objective To evaluate the association between AL and postoperative outcomes, including overall survival (OS), replase‐free survival (RFS), and cancer‐specific survival (CSS), and to identify factors associated with increased risk of leak. Methods This retrospective cohort study included 2217 patients with histologically confirmed Stage I–III colon adenocarcinoma who underwent curative‐intent resection with primary anastomosis across three tertiary centres (2009–2025). Patients with benign pathology, carcinoma in situ (Stage 0), metastatic disease, or missing follow‐up data were excluded. ALs were defined as clinically and/or radiologically confirmed disruptions occurring within 30 days postoperatively. No leaks were observed beyond this period. Outcomes were compared using Kaplan–Meier estimates and Cox regression models. Results ALs, either clinical or radiological, occurred in 2.0% of patients ( n = 44). Leaks were associated with significantly increased 30‐day mortality (6.8% vs. 0.4%, p < 0.001), reoperation (86.4% vs. 3.4%, p < 0.001), and hospital stay (median 21 vs. 7 days, p < 0.001). In multivariable analysis, AL independently predicted 30‐day mortality (AOR 13.6, 95% CI 9.9–18.6) and return to theatre (AOR 396.2, 95% CI 218.8–717.4). AL was associated with worse OS and DFS, but not CSS ( p = 0.66). Conclusions AL is an independent predictor of postoperative morbidity and long‐term nononcologic mortality in colon cancer patients. While OS and DFS were significantly reduced, CSS remained unaffected, a unique finding that challenges assumptions about leak‐related oncologic progression. These results suggest that excess mortality stems from systemic complications and care disruption rather than cancer recurrence. Preventive strategies and early leak detection in high‐risk patients are essential to improving outcomes.