Objectives: The current surveillance strategy in Barrett's esophagus (BE) uses only histological findings of the last endoscopy to assess neoplastic progression risk. As predictor values vary across endoscopies, single measurements may not be an accurate reflection. Our aim was to explore the value of using longitudinal evolutions (i.e. successive measurements) of histological findings (low-grade dysplasia (LGD)) and immunohistochemical biomarkers (p53 and SOX2) by investigating the association with Barrett's progression.
Methods: In this proof-of-principle study of a longitudinal dynamic risk estimation model with a multicenter cohort design, 631 BE patients from 15 Dutch hospitals who were under surveillance were included. Longitudinal dynamic values of LGD, p53, and SOX2 were included in a multivariate joint model to estimate the risk of high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC).
Results: Longitudinal evolutions of aberrant expression of p53 (HR 1.26, p<0.01) and SOX2 (HR 1.43, p<0.01) were associated with an increased HGD/EAC risk. We also found weak evidence of an association with the longitudinal evolution of the presence of LGD (HR 1.02, p = 0.12). The performance of the model was good (AUC 0.80-0.88). Using this model, for each future BE patient the probability of aberrant expression of biomarkers based on multiple longitudinal observations can be estimated. This probability is translated in progression risk, expressed as HR.
Conclusions: This study provides solid ground to further explore a paradigm shift from currently recommended fixed intervals towards personalized surveillance, in which tailored risk estimations and corresponding surveillance intervals can be updated at every FU endoscopy for individual BE patients.