Expanding screening criteria for Barrett’s esophagus beyond patients with gastroesophageal reflux disease could increase the proportion of Americans eligible for screening from 13% to 51%, according to Nicholas Shaheen, MD, MPH, who said the change would create major practical challenges for gastroenterology practices while increasing pressure to adopt nonendoscopic screening approaches.
During a lecture at Digestive Disease Week® (DDW) 2026, Dr. Shaheen, of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, reviewed emerging strategies for risk stratification in Barrett’s esophagus and esophageal adenocarcinoma, and focused on two questions: which patients should undergo screening and how physicians should approach surveillance once Barrett’s esophagus is diagnosed.
Current societal guidelines have largely converged on key risk factors for Barrett’s esophagus, he said, but the latest AGA clinical practice guideline differs from earlier recommendations by suggesting screening in patients with any three risk factors, even in the absence of reflux symptoms: being male, non-Hispanic white, age > 50 years, have a history of smoking, chronic gastroesophageal reflux disease, obesity, or family history of BE or esophageal adenocarcinoma.
The rationale, Dr. Shaheen said, is that approximately 40% of patients who develop esophageal adenocarcinoma do not report gastroesophageal reflux disease symptoms, meaning symptom-based screening misses a substantial proportion of cancers.
However, modeling studies applying those recommendations to the US population suggest the broader criteria would dramatically expand screening demand. According to a 2023 analysis cited by Dr. Shaheen, applying American College of Gastroenterology guidelines would make about 13% of Americans eligible for screening, whereas applying the newer AGA recommendations would raise that figure to 51%.
“We can’t get all the screening that we need to get done for colorectal cancer,” Dr. Shaheen said, noting that esophageal cancer is much less common, but expanded screening recommendations would still require far more endoscopies.
He said less invasive screening tools could help expand screening capacity and reviewed several devices that have shown promising results.
One of the best studied is the Cytosponge, a capsule containing a compressed sponge attached to a tether. After the capsule dissolves, the sponge is withdrawn through the esophagus to collect cells for analysis with trefoil factor 3 immunohistochemistry.
Dr. Shaheen highlighted a randomized pragmatic trial involving more than 13,500 patients assigned either to usual care or to an offer of Cytosponge testing in primary care settings. Patients offered Cytosponge had a tenfold increase in Barrett’s esophagus diagnoses compared with usual care, and investigators also detected cases of dysplasia and esophageal cancer.
Another minimally invasive approach, the EsoCheck balloon capsule device, uses a retractable balloon to collect esophageal cells while shielding the specimen from contamination during withdrawal. The collected cells are analyzed for methylation markers, including vimentin and CCNA1.
In a study involving 173 patients with and without Barrett’s esophagus, the assay achieved area-under-the-curve values of approximately 0.95 across analyses for Barrett’s esophagus and esophageal cancer. Combined methylation testing for vimentin or CCNA1 produced sensitivity and specificity rates of 95% and 91%, respectively.
Dr. Shaheen also discussed wide-area transepithelial sampling with three-dimensional analysis (WATS), an abrasive brush biopsy system that retrieves larger tissue fragments than conventional cytology techniques. Synthetic image stacking allows pathologists to evaluate thick tissue samples in three-dimensional sections, improving visualization of dysplasia-associated architectural abnormalities.
In a study of 36,355 patients with gastroesophageal reflux disease undergoing screening endoscopy, 6,829 had at least 1 cm of columnar-lined esophagus. Of those patients, 42% had intestinal metaplasia detected, and approximately half of the positive findings were identified only through WATS sampling.
Dr. Shaheen suggested the technology may reduce the need for repeat endoscopy in patients with suspected Barrett’s esophagus but nondiagnostic standard biopsies.
The role of surveillance endoscopy also remains under debate following publication of the Barrett’s Oesophagus Surveillance Study, or BOSS trial. The UK study randomized nearly 3,500 patients with Barrett’s esophagus either to surveillance endoscopy every 2 years or to endoscopy performed only when clinically indicated. Mean follow-up approached 13 years.
Investigators found no difference in overall survival or cancer-specific mortality between groups.
Still, Dr. Shaheen cautioned against interpreting the findings as definitive evidence against surveillance. Nearly 60% of patients assigned to on-demand care ultimately underwent endoscopy. Within that group, the amount of endoscopy performed exceeded what would have been recommended under standard screening guidelines. In addition, about one-quarter of enrolled patients lacked intestinal metaplasia and would not meet US diagnostic criteria for Barrett’s esophagus, potentially lowering observed cancer risk.
He said the findings should encourage physicians to scrutinize the quality of surveillance examinations rather than abandon surveillance altogether.
“If you don’t look, you don’t see,” Dr. Shaheen said, criticizing rapid examinations that fail to adequately inspect the esophagus.
Emerging biomarker tools may also refine surveillance strategies. Dr. Shaheen highlighted p53 immunohistochemistry, which identifies abnormal overexpression or absent staining patterns associated with progression risk. Studies suggest that abnormal p53 staining may increase the risk of developing cancer by about ten times.
He also reviewed TissueCypher, a multiplex immunofluorescence assay incorporating nine protein biomarkers and six morphologic features to generate a progression risk score. Reported sensitivities ranged from 29% to more than 50%, with hazard ratios greater than five for intermediate- and high-risk categories vs low-risk groups.
Methylation-based biomarkers may represent the most active area of current research, he said. In one study involving 240 patients, increasing methylation risk scores correlated with progressively higher risks for neoplastic progression.
Dr. Shaheen predicted that future care pathways may rely heavily on nonendoscopic testing performed in primary care settings, followed by biomarker-driven triage to surveillance or endoscopic eradication therapy.
“If you’re a young person in the audience and you want to study a topic where your work could make a difference, this is a good place to go,” he said.
Dr. Shaheen disclosed receiving research grants from Lucid, GIE, Pentax, CDx Medical, Steris, Phathom, and Aqua. He also serves as a principal investigator for Medtronic and Exact Sciences and as a consultant for Cook.
DDW is AGA’s annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.