Adjunctive Techniques for Screening, Surveillance, and Risk Classification of Barrett Esophagus and Esophageal Dysplasia

POLICY NUMBER

A.7.01.167

DESCRIPTION

Several adjunctive technologies and tests are available for screening, surveillance, and risk stratification of Barrett esophagus (BE). The wide-area transepithelial sampling with three-dimensional analysis (WATS3D) is performed during the endoscopic examination of the esophagus, using a computer-assisted brush biopsy procedure as an adjunct to standard four-quadrant forceps biopsy. TissueCypher is a tissue systems pathology test that analyzes biopsy samples to predict the risk of progression to high-grade dysplasia or esophageal adenocarcinoma in patients with BE. BarreGen is a molecular test designed to assess mutational load in BE patients. EsoCheck is a non-endoscopic cell collection device used in conjunction with EsoGuard, a DNA methylation test, to detect BE and esophageal dysplasia. These technologies and tests are intended to complement standard procedures in the screening, surveillance, and risk stratification of individuals with BE or at risk of developing BE.

Barrett Esophagus

Barrett esophagus (BE) is a condition in which the squamous epithelium that normally lines the esophagus is replaced by specialized columnar-type epithelium known as intestinal metaplasia in response to irritation and injury caused by gastroesophageal reflux disease (GERD). Barrett esophagus occurs in the distal esophagus. It may involve any length of the esophagus, be focal or circumferential, and is visualized on endoscopy with a different color than background squamous mucosa. Confirmation of BE requires a biopsy of the columnar epithelium and microscopic identification of intestinal metaplasia. The prevalence of BE in the United States is estimated at 5.6%. Risk factors associated with the development of BE include GERD, male gender, central obesity, and age over 50 years. The diagnosis of GERD is associated with a 10% to 15% risk of BE. However, a population-based analysis from Sweden observed that 40% of the study cohort with esophageal cancer reported no prior history of GERD symptoms.

Cancer Risk and Management

Intestinal metaplasia is a precursor to esophageal adenocarcinoma, and patients with BE are at a 40-fold increased risk for developing this disease compared to the general population.

However, there are few data to guide recommendations about management and surveillance, and many issues are controversial. Guidelines from the American College of Gastroenterology (ACG) and a consensus statement from an international group of experts (Benign Barrett's and CAncer Taskforce) on the management of BE are published. The ACG recommendations for surveillance are stratified by the presence and grade of dysplasia.

When no dysplasia is detected, ACG has reported the estimated risk of progression to cancer ranges from 0.2% to 0.5% per year and endoscopic surveillance every 3 to 5 years is recommended. For low-grade dysplasia, the estimated risk of progression is 0.7% per year, and endoscopic therapy is preferred; however, endoscopic surveillance every 12 months is considered an acceptable alternative. It is recommended that both options are discussed with the patient. Precise estimates of cancer risk are not available for individuals with low-grade dysplasia due to large disparities among studies on its natural history. Interobserver variability in the diagnosis of low-grade dysplasia with standard biopsy may be responsible, with expert pathologists commonly downgrading initial diagnoses made by community pathologists.

The Benign Barrett's and CAncer Taskforce consensus group did not endorse routine surveillance for people without dysplasia and was unable to agree on surveillance intervals for low-grade dysplasia.

For high-grade dysplasia, the estimated risk of progression is about 7% per year, and ACG has recommended endoscopic eradication therapy, with the type of procedure dependent on patient age and life expectancy, comorbidities, the extent of dysplasia, local expertise in surgery and endoscopy, and patient preference. Approximately 40% of patients with high-grade dysplasia on biopsy are found to have associated carcinoma in the resection specimen.

For patients who are indefinite for dysplasia, a repeat endoscopy should be performed at 3 to 6 months following optimization of acid suppressive medications. A surveillance interval of 12 months is recommended if an indefinite for dysplasia reading is confirmed on repeat endoscopy in these individuals. Many patients who are indefinite for dysplasia show regression to nondysplastic BE with subsequent endoscopic evaluation. It is unclear whether some cases of regression are observed due to sampling error.

On May 31, 2019, the FDA approved Lucid Diagnostics Inc.'s EsoCheck Cell Collection Device (K222366) for use in collecting and retrieving surface cells of the esophagus in adults and adolescents aged 22 years and older (product code: EOX). An update to the PMA (K230339) was posted on February 7, 2023 which provided a revised indication for the use in the collection and retrieval of surface cells of the esophagus in the general population of adults and adolescents, 12 years of age and older.

BarreGEN assesses the degree of cumulative genetic derangement of the following 10 genetic loci of tumor suppressor genes (in parentheses), specifically assessing the presence of loss of heterozygosity mutations and new alleles consistent with microsatellite instability: 1p (CMM1, L-myc), 3p (VHL, HoGG1), 5q (MCC, APC), 9p (CDKN2A), 10q (PTEN, MXI1), 17p (TP53), 17q (RNF43, NME1), 18q (SMAD4, DCC), 21q (TFF1, PSEN2) and 22q (NF2).

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). EsoGuard (Lucid Diagnostics), TissueCypher (Castle BioSciences), and WATS3D (CDx Diagnostics), formerly known as EndoCDx, are available under the auspices of the CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

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POLICY

Wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is considered investigational for all indications, including but not limited to the screening and surveillance of Barrett esophagus and esophageal dysplasia.

EsoCheck and Esoguard are considered investigational for the screening and surveillance of Barrett esophagus and esophageal dysplasia.

TissueCypher is considered investigational for assessing the risk of progression to high-grade dysplasia or esophageal adenocarcinoma in individuals with Barrett esophagus.

BarreGen is considered investigational for assessing the risk of progression to high-grade dysplasia or esophageal adenocarcinoma in individuals with Barrett esophagus.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

05/15/2022: New policy added. Approved by the Medical Policy Advisory Committee.

10/18/2022: Policy reviewed; no changes.

10/05/2023: Policy reviewed; no changes.

01/22/2025: Policy title changed from "Adjunctive Techniques for Screening and Surveillance of Barrett Esophagus and Esophageal Dysplasia" to "Adjunctive Techniques for Screening, Surveillance, and Risk Classification of Barrett Esophagus and Esophageal Dysplasia." Policy description updated regarding tests and devices. Added investigational policy statements for EsoCheck and Esoguard, TissueCypher, and BarreGen. Code Reference section updated to add CPT codes 81479, 0108U, and 0114U.

SOURCE(S)

Blue Cross Blue Shield Association policy # 7.01.167

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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