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.