Effect of Anastomotic Leak on Long-Term Survival After Esophagectomy: Multivariate Meta-analysis and Restricted Mean Survival Times Examination

Background: Anastomotic leak (AL) is a serious complication after esophagectomy. It is associated with prolonged hospital stay, increased costs, and increased risk for 90-day mortality. Controversy exists concerning the impact of AL on survival. This study was designed to investigate the effect of AL on long-term survival after esophagectomy for esophageal cancer. Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched through October 30, 2022. The included studies evaluated the effect of AL on long-term survival. Primary outcome was long-term overall survival. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. Results: Thirteen studies (7118 patients) were included. Overall, 727 (10.2%) patients experienced AL. The RMSTD analysis shows that at 12, 24, 36, 48, and 60 months, patients not experiencing AL live an average of 0.7 (95% CI 0.2–1.2; p < 0.001), 1.9 (95% CI 1.1–2.6; p < 0.001), 2.6 (95% CI 1.6–3.7; p < 0.001), 3.4 (95% CI 1.9–4.9; p < 0.001), and 4.2 (95% CI 2.1–6.4; p < 0.001) months longer compared with those with AL, respectively. The time-dependent HRs analysis for AL versus no AL shows a higher mortality hazard in patients with AL at 3 (HR 1.94, 95% CI 1.54–2.34), 6 (HR 1.56, 95% CI 1.39–1.75), 12 (HR 1.47, 95% CI 1.24–1.54), and 24 months (HR 1.19, 95% CI 1.02–1.31). Conclusions: This study seems to suggest a modest clinical impact of AL on long-term OS after esophagectomy. Patients who experience AL seem to have a higher mortality hazard during the first 2 years of follow-up.