Long-term oncologic outcomes associated with clinically significant anastomotic leakage after curative colorectal cancer surgery: Stage- and location-stratified analyses

Background Clinically significant anastomotic leakage (AL) after colorectal cancer surgery is associated with substantial postoperative morbidity, but its long-term oncologic impact remains uncertain. We evaluated the association of AL with long-term survival, including stage- and location-specific patterns, after curative colorectal cancer surgery. Methods We retrospectively reviewed consecutive patients who underwent curative surgery for non-metastatic colorectal adenocarcinoma between 2004 and 2018. Clinically significant AL was defined as grade B or C leakage. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan–Meier and multivariable Cox regression analyses. Subgroup and formal interaction analyses were performed according to tumor stage and location. Results Among 2,122 patients, 63 (3.0%) developed clinically significant AL. After multivariable adjustment, including treatment era, AL was not independently associated with OS (HR, 1.581; 95% CI, 0.923–2.707; p = 0.095) or DFS (HR, 1.325; 95% CI, 0.812–2.161; p = 0.260). In stage III disease, patients with AL had lower 5-year OS (56.3% vs. 76.3%; p = 0.005) and DFS (43.9% vs. 68.4%; p = 0.007). However, formal interaction testing showed no significant effect modification by tumor stage (OS, p for interaction = 0.132; DFS, p for interaction = 0.141) or tumor location (OS, p for interaction = 0.775; DFS, p for interaction = 0.748). Conclusions Clinically significant AL was not independently associated with long-term oncologic outcomes in the overall cohort. Although poorer survival was observed in the stage III subgroup, the absence of significant interaction indicates that these stage- and location-specific findings should be interpreted as exploratory rather than evidence of differential AL effects.