The Impact of Anastomotic Leak After Esophagectomy on Long-term Survival in the Modern Era of Management (ALES Study)

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OBJECTIVE: To determine the impact of severity of esophageal anastomotic leak (AL), standardized by ECCG grading, on long-term survival within a contemporary multicenter cohort. SUMMARY BACKGROUND DATA: Historical evidence suggesting AL is associated with increased recurrence and poor survival is limited by heterogeneous definitions and outdated management. This study utilizes the standardized ECCG definition to evaluate the prognostic significance of AL severity under modern perioperative protocols and endoscopic rescue strategies. METHODS: An international multicenter cohort across 17 high-volume European centers. Adult patients with esophageal or junctional cancer treated with neoadjuvant CROSS or FLOT, followed by esophagectomy were included (2018-2023). RESULTS: Out of 2905 patients, 425 (14.6%) developed an AL. AL was associated with a nearly two-fold increase in pulmonary complications (46.8% vs. 26.7%; P<0.001). AL requiring surgical reintervention (type III) was associated with an increased 30- and 90-days mortality rate (7.3% vs. 2.7% and 12.3% vs. 4%, P<0.001) and a significant reduction in median overall survival versus the no leak group (33.9 vs. 69.3; months P<0.001). After multivariable adjustment, type III AL was associated with a greater likelihood of death (HR 1.51; 95% CI: 1.04-2.18; P=0.029). A lower rate of adjuvant therapy administration (33.9% vs. 43.3%; P=0.004) was observe for AL patients. No significant survival deficits were observed for leaks treated conservatively or with no-surgical intervention. CONCLUSIONS: AL requiring surgical reintervention was associated with impaired survival. This relationship identifies a high-risk clinical profile and represents a critical target for future research into strategies for clinical stabilization and risk mitigation.

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