Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

Nastazja Dagny Pilonis,Peter D Sasieni,W Keith Tan,Danielle L Morris,Rosemary Phillips,Rebecca C Fitzgerald,Craig Vickery,Maria O'Donovan,Massimiliano Di Pietro,Sarah Killcoyne,Rehan Haidry,Shalini Malhotra,Irene Debiram-Beecham,Jacobo Ortiz-Fernandez-Sordo,Tara Evans,Monika Tripathi,Ahmad Miremadi,Abigail Kerridge,Jon Harrison

doi:10.1016/s1470-2045(21)00667-7

Abstract

SummaryBackgroundEndoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.MethodsWe first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance.FindingsThe prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia.InterpretationCytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways.FundingMedical Research Council, Cancer Research UK, Innovate UK.

Highlights

Oesophageal adenocarcinoma is a public health concern due to increasing incidence rates; as it generally presents at an advanced stage, there is a poor 5-year overall survival of less than 20%, with little improvement over the past 30 years.[1,2] Barrett’s oesophagus is a precancerous lesion that increases the risk of oesophageal adenocarcinoma through intermediary stages of increasing morphological abnormality on histology, described as non-dysplastic Barrett’s oesophagus, low-grade dysplasia, high-grade dysplasia, and invasive adenocarcinoma.[3]
We included all available consecutive patients older than 18 years with a confirmed diagnosis of Barrett’s oesophagus
As previous analyses reported significant differences in age and Barrett’s segment length in patients with and without dysplasia, we evaluated those www.thelancet.com/oncology Vol 23 February 2022

Summary

Introduction

Oesophageal adenocarcinoma is a public health concern due to increasing incidence rates; as it generally presents at an advanced stage, there is a poor 5-year overall survival of less than 20%, with little improvement over the past 30 years.[1,2] Barrett’s oesophagus is a precancerous lesion that increases the risk of oesophageal adenocarcinoma through intermediary stages of increasing morphological abnormality on histology, described as non-dysplastic Barrett’s oesophagus, low-grade dysplasia, high-grade dysplasia, and invasive adenocarcinoma.[3]. Evidence before this study We searched PubMed from March 1, 2019, to July 31, 2019, for publications in English on non-endoscopic surveillance in Barrett’s oesophagus, using the terms “Barrett’s (o)esophagus” AND “surveillance” AND “non-endoscopic”. This search retrieved nine articles, seven of which were reviews. As earlier detection vastly improves outcomes in oesophageal adenocarcinoma, patients with the precursor lesion Barrett’s oesophagus are recommended to undergo regular endoscopic surveillance to detect and treat early neoplasia. Endoscopic surveillance is recommended for patients with Barrett’s oesophagus because, the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett’s oesophagus

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