THE IMPACT OF ANASTOMOTIC LEAK AFTER ESOPHAGECTOMY ON LONG-TERM SURVIVAL IN THE MODERN ERA OF MANAGEMENT (ALES STUDY): A MULTICENTER COHORT STUDY
Sheraz Markar1, Lorenzo Giorgi1, Nadia Guidozzi1, Riadh Salem1, Kerry Chou11. John Radcliffe Hospital, Oxford, England, United Kingdom.
Background
Anastomotic leak (AL) remains a serious complication after esophagectomy. Older studies suggested AL increases locoregional recurrence and reduces survival. With modern perioperative pathways and endoscopic rescue strategies transforming AL management, this international study assessed the impact of AL and its severity on survival.
Study Design
A multicenter cohort from 14 European high-volume hospitals (2018â€"2023). Consecutive adults with esophageal or Siewert I/II junctional cancer treated with neoadjuvant CROSS or FLOT followed by curative-intent esophagectomy were included. AL was defined/graded per ECCG. Primary outcomes were overall (OS) and disease-free survival (DFS).
Statistical Analysis
Categorical variables were compared with chi-square / Fisher’s exact tests and continuous variables with t-test or Wilcoxon rank-sum. OS and DFS were calculated from surgery; survival curves were compared using log-rank tests with Holm-adjusted pairwise comparisons. Multivariable Cox models reported HRs with 95% CIs. Complete-case analysis was performed, with a sensitivity analysis incorporating discharge WBC and CRP.
Results
Of 2331 patients, exclusions (â"°Â¤90-day mortality, R+ margins, pM1) left 1999 for survival analysis. AL occurred in 329 (16.5%): Type I (3.4%), Type II (8%), Type III (5.2%). Pulmonary complications were more common with AL (p<0.001). OS at 1/3/5 years was: No leak 88.8/64.4/50.8%; Type I 87.5/73.4/55.9%; Type II 88.5/58.2/56.6%; Type III 80.2/49.6/36.4%. Kaplanâ€"Meier curves differed overall (p=0.021), but only Type III vs No leak remained significant after adjustment (p=0.018). DFS at 1/3/5 years was: No leak 79.1/59.2/52.6%; Type I 73.6/60.4/60.4%; Type II 84.4/57.7/55.0%; Type III 74.4/36.9/34.1%. After adjustment, only Type III differed significantly vs No leak (p=0.006) and vs Type II (p=0.007).
Univariable predictors of poorer OS included stage IIIâ€"IV, male sex, smoking, age, ASA IIIâ€"IV, diabetes, pulmonary complications, CROSS protocol, and higher discharge WBC. Type III AL was associated with worse OS (HR 1.61; p=0.003) and DFS (HR 1.63; p=0.001). In multivariable models excluding pulmonary complications as a mediator, Type III remained independently associated with poorer OS (HR 1.52; p=0.047). Inflammation-adjusted analysis showed Type III predicted worse DFS (HR 1.80; p=0.033); WBC remained associated with OS (HR 1.07; p=0.008), while CRP was not.
Discussion
In this large modern cohort, only Type III leaks were linked to reduced survival, supporting the idea that contemporary management mitigates the oncologic impact of AL. Elevated discharge WBC emerged as an independent prognostic factor, suggesting a biological connection between systemic inflammation and poorer outcomes after major complications.
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