Prognostic impact of body mass index stratified by smoking status in patients with esophageal adenocarcinoma

Purpose: Given that smoking affects body mass index (BMI) and survival, stratification by smoking status may be required to determine the true prognostic impact of BMI. Although obesity increases risk for developing esophageal adenocarcinoma (EAC), the prognostic influence of obesity and its potential modification by smoking status is unknown in this disease. Patients and Methods: All patients (N = 778) underwent potentially curative esophagectomy. BMI was calculated using measured height and weight at surgery and categorized as obese (≥ 30 kg/m ²), overweight (25 to 29.9 kg/m ²), or normal (18.5 to 24.9 kg/m ²). Cigarette smoking was categorized as never or ever. The association of BMI with disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) was determined by Cox regression. Results: Excess BMI was significantly associated with DSS in a manner that differed substantially by smoking status (P for interaction = .023). Among never smokers, obesity was significantly associated with adverse DSS (hazard ratio [HR] = 2.11; 95% CI, 1.31 to 3.43; P = .002), DFS (HR = 2.03; 95% CI, 1.30 to 3.18; P = .002), and OS (HR = 1.97; 95% CI, 1.24 to 3.14; P = .004), as compared with normal weight, after adjusting for covariates. By contrast, among ever smokers, obesity was not prognostic, and overweight status was significantly associated with favorable survival in univariate, but not multivariate, analysis. Conclusion: Obesity among never smokers was independently associated with two-fold worsening of DSS, DFS, and OS after surgery for EAC, after adjusting for known prognostic factors. These data, in one of the largest reported resected EAC cohorts, are the first to show an adverse prognostic impact of obesity in EAC.