Risk of esophageal cancer in achalasia: A matched cohort study utilizing the Nationwide Veterans Affairs Achalasia Cohort (VA-AC)

Abstract: INTRODUCTION: Achalasia is a postulated risk factor for esophageal cancer (EC); however, EC-associated risk in achalasia is understudied. We aimed to evaluate EC risk among individuals within the nationwide Veterans Affairs Achalasia Cohort (VA-AC). METHODS: We conducted a matched cohort study among US Veterans ≥18 years from 1999-2019. Individuals with achalasia were age- and sex-matched 1:4 to individuals without achalasia. Follow-up continued from study entry until diagnosis with incident/fatal EC (primary outcome), death from non-EC related causes, or end of the study follow up (12/31/2019). Association between achalasia and EC risk was examined using Cox regression models. RESULTS: We included 9,315 individuals in the analytic cohort (median age 55 years; 92% male): 1,863 with achalasia matched to 7,452 without achalasia. During median 5.5 years follow-up, 17 esophageal cancers occurred (3 esophageal adenocarcinoma (EAC), 12 squamous cell carcinoma (SCC), 2 unknown-type) among individuals with achalasia, compared to 15 esophageal cancers (11 EAC, 1 SCC, 3 unknown-type) among those without achalasia. EC incidence for those with achalasia was 1.4 per 1,000 person-years, and median time from achalasia diagnosis to EC development was 3.0 years (Q1-Q3: 1.3-9.1). Individuals with achalasia had higher cumulative EC incidence at 5, 10, and 15-years follow-up compared to individuals without achalasia, and EC risk was 5-fold higher (hazard ratio 4.6, 95% CI 2.3-9.2). DISCUSSION: Based on substantial EC risk, individuals with achalasia may benefit from a high index of suspicion and endoscopic surveillance for EC.

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