Introduction
Screening for Barrett’s esophagus (BE) could lead to earlier detection (EAC) and improve survival of esophageal adenocarcinoma (EAC). The Cytosponge, a non-endoscopic cell collection device that is coupled with the biomarker Trefoil Factor 3 (TFF3), has been shown in the Barrett’s Esophagus Screening Trial 3 (BEST3) trial, to lead to a 10-fold increase in BE diagnosis in a reflux population. The aims of this study were to: 1) Estimate the proportion of missed BE or stage-1 EAC under the current primary care reflux referral pathway, 2) Define a target screening population and, 3) To estimate the trade-off between the target population to screen and the proportion of BE or stage-1 EAC diagnosed.
Aims & Methods
This was a retrospective analysis and modelling from the multicentre, pragmatic, randomised controlled BEST3 trial that took place across 109 general practices in England. The findings from the main study were previously reported.1 For aim 1, we used the BEST3 intervention (n=6834) and control arm (n=6388) data to estimate the number of missed BE or stage-1 EAC under the current reflux referral pathway. For aim 2, we determined which clinical risk factors predict a diagnosis of BE or stage-1 EAC in individuals who swallowed the Cytosponge (n=1654) and then modelled the probability of a diagnosis of BE and stage-1 EAC. For aim 3, we used different probabilities of a diagnosis of BE and stage-1 EAC to estimate the starting age to screen, to estimate the trade-off of the number-needed-to-screen and the proportion of BE or stage-1 EAC that would be diagnosed.
Results
Among usual care (control), 0.2% (13/6388) of individuals had BE or stage-1 EAC whereas, the expected prevalence of BE or stage-1 EAC within the intervention (Cytosponge) arm was 10.6% (680/6388), leading to the estimation that the proportion of missed pre-symptomatic BE and stage-1 EAC cases under current care is ~98%. Using logistic regression, we showed that male gender (Odds Ratio, OR 2.46, 95% Confidence Interval, CI 1.67-3.64, p<0.001), age (OR 1.05, 95% CI 1.03-1.07, p<0.001) and family history (OR 1.81, 95% CI 1.04-3.15, p=0.036) were significant predictors of BE or stage-1 EAC diagnosis. Next we modelled and simulate the trade-off for the numbers-needed-to screen on a population level according to different probability thresholds for a diagnosis of BE or stage-1 EAC (≥3%, ≥5%, and ≥10% among individuals with reflux). For these models we set an upper age limit of 74 years for practical considerations (Table 1). These data suggest that a 5% threshold is likely the optimal strategy. This reduces the screening population by 45.2% (males age 55-74 and females 65-74) while still diagnosing 71.0% of cases with a number-needed-to-screen to detect one case of 10.7.
Conclusion
A targeted screening strategy has the potential to substantially improve detection rates for BE and stage-1 EAC compared with current care. The trial data can be used to inform the optimal age for screening in males versus females in order to maximise the yield of screening according to the resources available.
References
Fitzgerald RC, di Pietro M, O'Donovan M, et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. The Lancet 2020;396(10247):333-44.
Disclosure
R.C.F. and M.O. are named inventors on patents pertaining to the Cytosponge and associated technology. R.C.F. and M.O are shareholders of Cyted Ltd., a company working on early detection technology. The other authors declare no conflict of interest.