Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study

Background: Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER). Methods: This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1-9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed. Findings: Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3-176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31-0.88; HR 0.44, 95% CI: 0.25-0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07-0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction. Interpretation: Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER. Funding: National Cancer Center Research and Development Fund 36, Japan.