The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence

Background: The incidence of esophageal adenocarcinoma is rising dramatically. This increase may reflect increased disease burden, reclassification of related cancers, or overdiagnosis resulting from increased diagnostic intensity, particularly upper endoscopy for patients with gastroesophageal reflux disease or Barrett esophagus. Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to extract information on incidence, stage distribution, and disease-specific mortality for esophageal adenocarcinoma as well as information on related cancers. Results: From 1975 to 2001, the incidence of esophageal adenocarcinoma rose approximately sixfold in the United States (from 4 to 23 cases per million), a relative increase greater than that for melanoma, breast, or prostate cancer. Reclassification of squalmous cell carcinoma is an unlikely explanation for the rise in incidence, because the anatomic distribution of esophageal cancer in general has changed. The only location with increased incidence is the lower third of the esophagus-the site where adenocarcinoma typically arises. Reclassification of adjacent gastric cancer is also unlikely because its incidence has also increased. Because there has been little change in the proportion of patients found with in situ or localized disease at diagnosis since 1975 (from 25% to 31%) and because esophageal adenocarcinoma mortality has increased more than sevenfold (from 2 to 15 deaths per million), overdiagnosis can be excluded as an explanation for the rise in incidence. Conclusion: The rising incidence of esophageal adenocarcinoma represents a real increase in disease burden.