In Patients with Non-Dysplastic Barrettʼs Esophagus (NDBE), Selective Endoscopic Ablative Therapy (EAT) Based on Risk-Stratification by Molecular Analysis of Mutational Load (ML) is the Most Cost-Effective Management Strategy

Abstract

Purpose: Long-term surveillance of NDBE has high cost and limited effectiveness in preventing esophageal adenocarcinoma, and EAT for NDBE remains expensive and controversial. Recent studies support a role for molecular markers in defining a subset of patients at greater risk for progression to cancer. Aim: To evaluate cost-effectiveness of EAT of NDBE using risk-stratification with molecular markers. Methods: Using a Markov hybrid decision tree, 4 competing strategies were evaluated in a hypothetical 50-year old cohort of patients with NDBE over their lifetime with societal perspective. In strategy I, all patients with NDBE were followed without specific intervention; in strategy II standard surveillance according to the ACG practice guidelines was performed, with EAT used for patients with high grade dysplasia. In strategy III, EAT was performed in all patients with NDBE. In strategy IV, the PathFinder assay (RedPath Integrated Pathology, Pittsburgh, PA), which assesses mutational load (ML, a semi-quantative measure of genomic instability using loss of heterozygosity mutations in DNA extracted from areas targetted by microdissection from biopsy slides) was used for risk-stratification (Gastroenterol 2012;142 (5):S 749). Patients with no ML (25%) underwent minimal surveillance, patients with low ML (70%) underwent standard surveillance and patients with high ML (5%) were treated selectively by EAT. The model was biased against EAT with conservative estimates of complete response to EAT and continued surveillance afterwards. Transitional probabilities, discounted cost and utility values to estimate quality adjusted life-years (QALY) were obtained from published information and Medicare reimbursement data. Incremental Cost-Effectiveness Ratio (ICER) of different strategies was the main outcome measure. Results: In baseline analysis, strategy IV was clearly dominant (both cheaper and more effective: Table), and sensitivity analyses showed the conclusion to be robust to plausible ranges of parameters. In a second-order Monte Carlo analysis, under strategy IV and III, 45 and 114 esophageal cancers developed over 18,504 and 17,825 person-years of follow-up, respectively [RR 0.39 (95% CI, 0.28 to 0.55); NNT of 14 (95% CI, 11-22)]. Critical determinants of cost-effectiveness of the risk-based strategy were rate of complete response and cost of ablation and, surveillance interval in patients with no ML.Table: [1448] TableConclusion: Use of ML to stratify risk in NDBE patients was the most cost-effective strategy to prevent esophageal adenocarcinoma. Targeting EAT towards patients with high ML presents an opportunity for a paradigm shift in the management of NDBE. Disclosure: Dr. Das: consultant; Mr. Ellsworth, Dr. Smith, Dr. Finklestein: Employee. This research was supported by an industry grant from Research support by RedPath Integrated Pathology, Inc, Pittsburgh, PA.