Understanding Cancer Incidence in Barrett’s Esophagus: Light at the End of the Tunnel

The main importance of Barrett's esophagus, a metaplastic change in the epithelial lining of the esophagus, is that its presence is a harbinger of increased risk of esophageal adenocarcinoma. Given the rapidly increasing incidence of esophageal adenocarcinoma, the management of Barrett's esophagus becomes a prominent clinical question. 2. Does the risk differ between patients with vs those without intestinal metaplasia on biopsy? The authors report that cancer risk is statis- tically significantly lower in persons without intestinal meta - plasia (vs with metaplasia) on the initial biopsy. Furthermore, their incidence figures suggest that persons who are consistently without intestinal metaplasia, after repeated sampling, are even more unlikely to develop cancer. 3. Does the risk change over time? Almost all cost-effectiveness models assume that the risk of cancer progression is constant over time; the current study is among the first adequately powered evalua - tions to show that cancer detection is relatively steady over time. 4. Does the risk vary by age and sex? Current clinical recommenda- tions imply that surveillance, if performed, would likely provide the greatest benefit to men and to persons older than 50 years. The current study supports these hypotheses by finding that the risk of esophageal cancer is substantially higher among men than women and among older persons compared with those who are younger than 50 years. This important study, however, still leaves several important gaps mainly because the investigators lacked detailed endoscopic data. The presence of a visually abnormal esophageal lining is a crucial requirement for diagnosing Barrett's esophagus in most clin- ical studies. For the current study, entry into the cohort required only columnar mucosa on an esophageal biopsy; it is unclear how many patients actually had visible changes of Barrett's esophagus on endoscopy. Such misclassification could meaningfully bias the results: if a moderate proportion did not have visible changes, and if the risk in that group was lower than among persons who had visible changes, then the average cancer risk may be artificially low. The finding that a relatively small proportion of patients had more than one endoscopic examination was interesting because it raises the possibility that some subclinical cancers might remain undetected. Undetected cancers might partly explain the difference in cancer incidence between this study and others from centers that use vigorous regular endoscopic surveillance programs. It is unknown what proportion of such cancers would cause clinical disease, especially among more elderly patients with competing causes of mortality. In summary, the current study, which was conducted in a large general population, provides general support for many paradigms underlying current thoughts about the management of Barrett's esophagus (6). First, patients without intestinal metaplasia, and especially patients with multiple examinations who lack meta- plasia, are at relatively low risk of malignant progression; such patients are less likely to benefit from surveillance or treatment.