Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Using the Nationwide Veterans Affairs Achalasia Cohort

INTRODUCTION: Achalasia is a postulated risk factor of 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. METHODS: We conducted a matched cohort study among US veterans aged 18 years or older from 1999 to 2019. Individuals with achalasia were age matched 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 (December 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 a median 5.5 years of follow-up, 17 EC occurred (3 esophageal adenocarcinoma, 12 squamous cell carcinoma, and 2 unknown type) among individuals with achalasia, compared with 15 EC (11 esophageal adenocarcinoma, 1 squamous cell carcinoma, and 3 unknown type) among those without achalasia. EC incidence for those with achalasia was 1.4 per 1,000 person-years, and the 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 of follow-up compared with individuals without achalasia, and EC risk was 5-fold higher (hazard ratio 4.6, 95% confidence interval: 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.