ASO Visual Abstract: 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.