Researchers identify three risk factors that predict malignant progression of Barrett esophagus

Independent predictors of malignant progression of Barrett esophagus (BE) are BE segment length, the presence of low-grade dysplasia, and nodularity, according to a large prospective study by researchers from Mayo Clinic in Rochester, MN, and Scottsdale, AZ, and published in Journal of Clinical Gastroenterology.

“The increased risk of progression associated with increasing BE length and visible nodules highlights importance of careful endoscopic examination in BE subjects to assess progression risk in individual subjects,” the investigators advised. “These factors could help identify high-risk BE subjects who would benefit from endoscopic therapy rather than surveillance.”

Despite surveillance programs for BE, the incidence of esophageal adenocarcinoma in the United States has risen by as much as six-fold annually over the past decade, noted the authors. The sequence of progression of BE starts with columnar epithelium that progresses to low-grade dysplasia, followed by progression to high-grade dysplasia, and finally carcinoma. The risk of progression to esophageal carcinoma is known to rise with increasing grade of dysplasia.

The researchers sought to identify demographic, clinical, endoscopic, and histologic features that predict malignant progression from non-dysplastic BE or low-grade dysplasia to high-grade dysplasia or esophageal adenocarcinoma in a prospective cohort of 318 patients with non-dysplastic BE and 301 with low-grade dysplasia. The patients were identified from the Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry and were followed for an average of 5.3 years. Their mean age was 62.6 years and 85% were male.

Of the 619 patients included overall, seven with non-dysplastic BE and 21 with low-grade dysplasia progressed to high-grade dysplasia or esophageal adenocarcinoma over that time. The incidence rate of high-grade dysplasia/esophageal adenocarcinoma was 0.97% per person-year of follow-up in the entire cohort, 0.59% person-years in patients with non-dysplastic BE, and 1.23% person-years in those with low-grade dysplasia.

On multivariate analysis, BE length (hazard ratio [HR] 1.16); presence of nodularity (HR 4.98), and presence of low-grade dysplasia (HR 2.57) were significant predictors of progression to high-grade dysplasia/esophageal adenocarcinoma.

“The current study is unique in that it was performed using data from a multicenter registry with a large sample size, thereby increasing the reliability of the results,” the authors wrote, adding that the results are consistent with that of a meta-analysis published in 2017 in Clinical Gastroenterology and Hepatology. In that meta-analysis, older age, male sex, smoking, longer BE segment, and low-grade dysplasia were associated with the risk of BE progression. The Mayo Clinic study, however, found that demographic and lifestyle factors did not influence the risk of progression to high-grade dysplasia/adenocarcinoma.

The authors observed that recommendations from gastrointestinal (GI) societies advise that BE with dysplasia of any grade should be reviewed by at least one pathologist with expertise in GI pathology. “In the current study, all BE diagnoses were made by expert GI pathologists. This increases the confidence of association between BE-low-grade dysplasia and higher risk of progression identified in the current study,” they noted.

“In conclusion, in this large well-defined cohort of non-dysplastic BE and BE-low-grade dysplasia subjects, for all of whom esophageal biopsies were reviewed by expert GI pathologists, risk of progression to high-grade dysplasia/esophageal adenocarcinoma increases ∼three-fold in patients with BE-low-grade dysplasia as opposed to non-dysplastic BE,” the authors wrote.

The researchers acknowledged that type II error may have been a possible limitation of the study, given that there were few progressors in each group.