Nonendoscopic Screening for Barrett's Esophagus: Current Methods, Evidence, and Future Directions

The incidence of esophageal adenocarcinoma (EAC) has steadily risen over the past several decades. Screening for EAC and its metaplastic precursor, Barrett's esophagus (BE), remains a challenge to prevent EAC development and decrease EAC-attributed mortality. Unfortunately, most BE is diagnosed at the time of diagnosis of EAC in the majority of patients with EAC, showcasing that current screening paradigms are neither widely accepted nor adequate. Historically, screening for BE with upper endoscopy was endorsed by major gastrointestinal society guidelines in the presence of gastroesophageal reflux disease symptoms and related risk factors. However, this method has limitations, including accessibility, cost, and tolerability. Nonendoscopic technologies, such as swallowable cell collection devices, methylated DNA marker assays, esophageal capsule endoscopy, and emerging molecular and physiologic biomarkers, represent newer technologies that may offset many of the limitations of traditional endoscopic screening and facilitate translation to broader settings to capture higher-risk patients. In this review article, we aim to provide a comprehensive, up-to-date summary of nonendoscopic screening tools for BE, contextualizing their advantages, limitations, and prospects for clinical implementation.