Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Abstract

Background & aims: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis.

Methods: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM).

Results: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34-0.57; P<.001). In a multivariable analysis, BE with IM was associated with longer survival independent of patient age or sex, tumor stage or location, and BE length (adjusted HR, 0.66; 95% CI, 0.5-0.88; P=.005). In the United Kingdom cohort, patients BE and IM had a reduced risk of death compared with those without (HR, 0.59; 95% CI, 0.5-0.69; P<.001), with continued significance in multivariable analysis that included patient age and sex and tumor stage and tumor location (adjusted HR, 0.77; 95% CI, 0.64-0.93; P=.006).

Conclusion: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Keywords: Barrett Esophagus; Esophageal Adenocarcinoma; Esophagus; Survival.

Figure 1

Overall survival time in years comparing esophageal adenocarcinoma with and without BE/IM, (A): Mayo Clinic (P<0.001), (B): OCCAMS (P<0.001)

Figure 2

Forest plots for subgroup analysis HR in Mayo Clinic cohort for BE/IM vs non-BE/IM adjusting for age and sex including: (A) location based on Siewert classification, (B) TNM stage, (C) Surgery with/without neoadjuvant therapy.