Indefinite for Dysplasia in Barrett's Esophagus Carries Substantial Risk for Prevalent and Incident Neoplasia: Updated Outcomes and Long-Term Follow-up.

Objective: The optimal management of Barrett's esophagus (BE) patients with indefinite for dysplasia (IND) is unclear, due to uncertain risks of progression to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and esophageal adenocarcinoma (EAC). This study aimed to define the risks of neoplasia among IND patients, including long-term follow-up of our previously described cohort, and to identify risk factors for progression to neoplasia.

Methods: IND patients from 2000 to 2023 were identified from the University of Pennsylvania Health System pathology database and the Barrett's esophagus patient registry. Prevalent neoplasia was defined as LGD, HGD, or EAC occurring within one year of index EGD. Incident neoplasia occurred >1 year after index EGD. Time to neoplasia was analyzed via Cox proportional hazards regression model. Risk factors for neoplasia were identified via logistic and Cox regression.

Results: 299 patients were identified of whom, 223 had follow-up EGD within one year. Of these 223, 9.87% had prevalent neoplasia of any grade: LGD in 3.14%, HGD in 5.38%, and EAC in 1.35%. 217 patients without prevalent neoplasia had EGD after one year, with median follow-up of 4.37 years (IQR, 2.62-8.15); 22% developed incident neoplasia. Incidence of any neoplasia was 4.35 per 100 person-years; 2.43 for LGD, 1.24 for HGD, and 0.47 for EAC. BE length and smoking were associated with incident neoplasia (HR 1.13, 95% CI 1.03-1.25 and HR 2.01, 95% CI 1.12-3.80).

Conclusions: IND carries substantial risk for progression to neoplasia including HGD/EAC, especially in the first year after diagnosis. Incident HGD/EAC risk approximates that published for LGD.