Cancer incidence and mortality — Estimates of the annual cancer incidence in patients with Barrett's esophagus have ranged from 0.1 to almost 3.0 percent, with more recent studies suggesting rates closer to 0.1 to 0.4 percent per year [11-27]. Although the risk of developing esophageal cancer is increased at least 30-fold above that of the general population, the absolute risk of developing cancer for an individual patient with nondysplastic Barrett's esophagus is low [23]. The risk of developing cancer is higher among men, older patients, and patients with long segments of Barrett's mucosa [19,25,26,28-30].
Patients with Barrett's esophagus most often die from causes unrelated to esophageal cancer. This is likely because many patients with Barrett's esophagus are older, overweight, and succumb to common diseases, such as coronary artery disease, before developing esophageal adenocarcinoma. In a meta-analysis with 50 studies that included 14,109 patients, the mortality rate due to esophageal adenocarcinoma was 3.0 per 1000 person-years, whereas the mortality rate due to other causes was 37.1 per 1000 person-years [24].
Dysplasia as a marker of risk — Esophageal adenocarcinoma in patients with Barrett's esophagus is thought to evolve through a sequence of genetic alterations that are associated with dysplastic changes of progressive severity. However, few studies document the natural history of dysplasia, so the rate at which metaplasia progresses to dysplasia and cancer is unclear. The estimates of the risk of progression of dysplastic Barrett's esophagus to esophageal adenocarcinoma range from 0.2 to 14 percent per year and vary based on the baseline degree of dysplasia [17,28,31-42]. The reasons underlying the disparities in the reported rates of progression are unsettled, but may in part be due to referral bias and inclusion of patients with prevalent cancers in some of the reports [34,43]. The evolution of genetic changes leading from Barrett’s esophagus to adenocarcinoma is discussed in more detail, separately. (See "Barrett's esophagus: Pathogenesis and malignant transformation", section on 'Adenocarcinoma'.)
A meta-analysis that included 24 studies with 2694 patients who had low-grade dysplasia found that esophageal adenocarcinoma developed in 119 patients (4 percent) [31]. The pooled incidence rate for the development of esophageal adenocarcinoma was 0.54 percent per year (95% CI 0.32-0.76 percent). For the combined outcome of esophageal adenocarcinoma or high-grade dysplasia, the incidence rate was 1.73 percent per year.
Based on available reports, we estimate the following rates of progression to esophageal adenocarcinoma [17,28,31-41]:
●General population of patients with Barrett's esophagus: 0.25 percent per year.
●Low-grade dysplasia: The risk of cancer is poorly defined because there are large disparities among studies on the natural history of low-grade dysplasia. The reasons underlying these disparities are not entirely clear, but a major factor appears to be differences in how study pathologists diagnose low-grade dysplasia. "Expert" pathologists will usually downgrade a diagnosis of low-grade dysplasia made by community pathologists [36]. A meta-analysis estimates that patients with low-grade dysplasia progress to cancer at the rate of 0.54 percent per year [31], but the range of reported cancer risk is so high that precise estimates of cancer risk are not possible [32,41].
●Indefinite for dysplasia: As with low-grade dysplasia, the risk of cancer is poorly defined. Studies suggest it is between 0.2 to 1.2 percent per year [40,41].
●High-grade dysplasia: 4 to 8 percent per year.
