Feasibility and Diagnostic Accuracy of a Capsule-Sponge Device for Esophageal Squamous Neoplasia (EDEN Trial)

Endoscopic screening for esophageal squamous neoplasia (ESN) is effective, but invasive and resource-intensive. We evaluated a minimally invasive capsule-sponge sampling with p53 immunohistochemistry (p53-IHC) for the early detection of ESN.

In this prospective cross-sectional proof-of-concept study, participants from 3 predefined groups: (1) healthy controls; (2) high-risk individuals with prior head-and-neck cancer; and (3) patients with early-stage ESN scheduled for endoscopic treatment, underwent capsule-sponge sampling followed by high-definition endoscopy (reference diagnosis). Two expert pathologists, blinded to reference diagnoses, assessed cytologic atypia for features of intraepithelial neoplasia (IEN) along with p53 expression. Outcomes included diagnostic performance, safety, and patient acceptability (visual analog scale [VAS]).

Among 188 participants (mean age, 60.4 ± 12.8 years; 115 men [61.2%]), which included 105 controls, 65 high-risk individuals, and 18 patients with ESN (4 high-grade IENs and 14 early carcinomas), the capsule-sponge sampling was technically successful in 173 cases (92.0%). Atypical cytology alone achieved an accuracy of 94.2% (95% confidence interval [CI], 89.6%-96.8%), sensitivity of 83.3% (95% CI, 60.8%-94.2%), and specificity of 95.4% (95% CI, 90.9%-97.8%). Positive p53 status alone showed high specificity (97.4%; 95% CI, 93.5%-99.0%), but modest sensitivity (55.6%; 95% CI, 33.7%-75.4%). A dual-positive test (IEN-consistent atypia + positive p53-IHC) was associated with higher odds of neoplasia vs a dual-negative test (odds ratio, 161.1; 95% CI, 28.7-903.2). No adverse events occurred. Median acceptability was 5 (interquartile range, 4-7), indicating a neutral-to-favorable experience.

In this case-enriched cohort, the capsule-sponge was safe and feasible, and cytology with adjunct p53-IHC showed high accuracy for ESN/early esophageal squamous cell carcinoma. Validation in asymptomatic high-risk cohorts is warranted to define real-world performance and triage utility.

gov, Number: NCT04192695.