Endoscopic Radiofrequency Ablation or Cryoablation for Barrett Esophagus

POLICY NUMBER

A.2.01.80

DESCRIPTION

In Barrett esophagus (BE), the normal squamous epithelium is replaced by specialized columnar-type epithelium, known as intestinal metaplasia. Intestinal metaplasia is a precursor to adenocarcinoma and may be treated with mucosal ablation techniques such as radiofrequency ablation (RFA) or cryoablation.

Barrett Esophagus and Risk of Esophageal Carcinoma

The esophagus is normally lined by squamous epithelium. Barrett Esophagus (BE) is a condition in which the normal squamous epithelium is replaced by specialized columnar-type epithelium, known as intestinal metaplasia, in response to irritation and injury caused by gastroesophageal reflux disease. Occurring in the distal esophagus, BE may be of any length; it may be focal or circumferential and can be seen on endoscopy as being a different color than the background squamous mucosa. Confirmation of BE requires a biopsy of the columnar epithelium and microscopic identification of intestinal metaplasia.

Intestinal metaplasia is a precursor to esophageal adenocarcinoma, which is thought to result from a stepwise accumulation of genetic abnormalities in the specialized epithelium, resulting in the phenotypic expression of histologic features from low grade dysplasia (LGD), to high-grade dysplasia (HGD), to carcinoma. Two large epidemiologic studies published in 2011 reported the risk of progression to cancer in patients with BE. One reported the rate of progression to cancer in more than 8,000 patients with a mean duration of follow-up of 7 years (range, 1 to 20 years). The de novo progression to cancer from BE at 1 year was 0.13%. The risk of progression was reported as 1.4% per year in patients with LGD and 0.17% per year in patients without dysplasia. This incidence translates into a risk of 10 to 11 times that of the general population. The other study identified more than 11,000 patients with BE and, after a median follow-up of 5.2 years, it reported that the annual risk of esophageal adenocarcinoma was 0.12%. Detection of LGD on index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1,000 person-years, and the incidence rate among patients without dysplasia was 1.0 case per 1,000 person-years. Risk estimates for patients with HGD were slightly higher. The reported risk of progression to cancer in BE in older studies was much higher, with an annual incidence of risk of 0.4% to 0.5% per year, with risk estimated at 30 to 40 times that of the general population. Current surveillance recommendations have been based on these higher risk estimates.

There are challenges in diagnostically differentiating between nondysplastic BE and BE with LGD; they are important when considering treatment for LGD. Both sampling bias and interobserver variability have been shown to be problematic. Therefore, analysis of progression to carcinoma in BE with intestinal metaplasia versus LGD is difficult. Initial diagnosis of BE can also be a challenge with respect to histologic grading because inflammation and LGD can share similar histologic characteristics.

One approach to risk-stratify patients with an initial diagnosis of LGD has been to use multiple pathologists, including experts in gastrointestinal histopathology, to confirm the initial diagnosis of LGD. There is a high degree of interobserver variability among the pathology readings of LGD versus inflammatory changes, and the resultant variability in pathology diagnosis may contribute to the variable rates of progression of LGD reported in the literature. Kerkhof and colleagues (2007) reported that, in patients with an initial pathologic diagnosis of LGD, review by an expert pathologist would result in the initial diagnosis being downgraded to nondysplasia in up to 50% of cases. Curvers and colleagues (2010) tested this hypothesis in 147 patients with BE who were given an initial diagnosis of LGD. All pathology slides were read by 2 expert gastrointestinal pathologists with extensive experience in BE; disagreements among experts in the readings were resolved by consensus. Once this process was completed, 85% of initial diagnoses of LGD were downgraded to nondysplasia, leaving 22 (15%) of 147 patients with a confirmed diagnosis of LGD. All patients were followed for a mean of 5.1 years for progression to HGD or cancer. For patients with confirmed LGD, the rate of progression was 13.4%, compared with 0.5% for patients who had been downgraded to nondysplasia.

The strategy of having LGD confirmed by expert pathologists is supported by the results of a randomized controlled trial by Phoa and colleagues (2014), which required confirmation of LGD by a central expert panel following initial diagnosis by a local pathologist. Of 511 patients with an initial diagnosis of LGD, 264 (52%) were excluded because the central expert panel reassigned the classification of LGD, most often from LGD to indefinite or nondysplasia. These findings were further confirmed in a retrospective cohort study by Duits and colleagues (2015) who reported on 293 BE cases with LGD diagnosed over an 11-year period and submitted for expert panel review. In this sample, 73% of subjects were downstaged.

Management of Barrett Esophagus

The management of BE includes the treatment of gastroesophageal reflux disease and surveillance endoscopy to detect progression to high-grade dysplasia or adenocarcinoma. The finding of high-grade dysplasia or early-stage adenocarcinoma warrants mucosal ablation or resection (either endoscopic mucosal resection [EMR] or esophagectomy).

EMR, either focal or circumferential, provides a histologic specimen for examination and staging (unlike ablative techniques). One study provided long-term results for EMR in 100 consecutive patients with early Barrett-associated adenocarcinoma (limited to the mucosa).The 5-year overall survival was 98% and, after a mean of 36.7 months, metachronous lesions were observed in 11% of patients. A 2009 review stated that circumferential EMR of the entire segment of BE leads to a stricture rate of 50%, and recurrences occur at a rate of up to 11%.

Ablative Techniques

Available mucosal ablation techniques that include several thermal (multipolar electrocoagulation [MPEC], argon plasma coagulation [APC], heater probe, neodymium-doped yttrium aluminum garnet [Nd:YAG] laser, potassium titanyl phosphate [KTP]-YAG laser, diode laser, argon laser, and cryoablation) or nonthermal (5-aminolevulinic acid, photodynamic therapy) techniques. In a randomized phase 3 trial, photodynamic therapy was shown to decrease significantly the risk of adenocarcinoma in Barrett Esophagus. (Photodynamic therapy for Barrett Esophagus is discussed in a separate policy, Oncologic Applications of Photodynamic Therapy, Including Barrett’s Esophagus ).

Radiofrequency ablation affects only the most superficial layer of the esophagus (ie, the mucosa), leaving the underlying tissues unharmed. Measures of efficacy for the procedure are the eradication of intestinal metaplasia and post-ablation regrowth of the normal squamous epithelium. (Note: The eradication of intestinal metaplasia does not leave behind microscopic foci). The HALO system uses radiofrequency energy and consists of 2 components: an energy generator and an ablation catheter. Reports of the efficacy of the HALO system in ablating Barrett Esophagus have been as high as 70% (comparable with alternative methods of ablation [e.g., APC and MPEC]), and even higher in some reports. The incidence of leaving behind microscopic foci of intestinal metaplasia has been reported to be between 20% and 44% with APC and 7% with MPEC; studies using the HALO system have reported 0%. Another potential advantage to the HALO system is that it is an automated process that eliminates operator-dependent error, which may be seen with APC or MPEC. Cryotherapy allows for the treatment of uneven surfaces and can be administered as either a spray therapy or a balloon catheter.

The risk of treating high-grade dysplasia or mucosal cancer solely with ablative techniques is undertreatment for approximately 10% of patients with undetected submucosal cancer, in whom esophagectomy would have been required.

In 2005, the HALO360 (now Barrx™ 360 RFA Balloon Catheter; Barrx Medical; acquired by Covidien in 2012 [now Medtronic]) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process and, in 2006, the HALO90 (now Barrx™ 90 RFA Focal Catheter) received clearance. The FDA-labeled indications are for use in coagulation of bleeding and nonbleeding sites in the gastrointestinal tract and include the treatment of Barrett Esophagus. Other focal ablation devices from Barrx include the Barrx™ 60 RFA Focal Catheter, the Barrx™ Ultra Long RFA Focal Catheter, and the Barrx™ Channel RFA Endoscopic Catheter.

In 2007, the CryoSpray Ablation™ System (formerly the SprayGenix Cryo Ablation system; CSA Medical) was cleared for marketing by the FDA through the 510(k) process for use as a “cryosurgical tool for destruction of unwanted tissue in the field of general surgery, specifically for endoscopic applications.” The CryoBalloon Ablation System has also been cleared by the FDA through the 510(k) process for use as a cryosurgical tool in surgery for endoscopic applications, including ablation of BE with dysplasia. The next-generation C2 CryoBalloon Ablation System was introduced in 2018.

In 2002, the Polar Wand® device (Chek-Med Systems), a cryosurgical device that uses compressed carbon dioxide, was cleared for marketing by the FDA through the 510(k) process. Indications for use are “ablation of unwanted tissue in the fields of dermatology, gynecology, general surgery, urology, and gastroenterology.”

POLICY

Radiofrequency ablation may be considered medically necessary for the treatment of Barrett esophagus with high-grade dysplasia (see Policy Guidelines).

Radiofrequency ablation may be considered medically necessary for the treatment of Barrett esophagus with low-grade dysplasia, when the initial diagnosis of low-grade dysplasia is confirmed by 2 pathologists (see Policy Guidelines).

Radiofrequency ablation is considered investigational for the treatment of Barrett esophaguswhen the above criteria are not met, including but not limited to Barrett esophagus in the absence of dysplasia.

Cryoablation is considered investigational for the treatment of Barrett esophagus, with or without dysplasia.

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.

Radiofrequency ablation for Barrett esophagus with high-grade dysplasia may be used in combination with endoscopic mucosal resection of nodular or visible lesions. The diagnosis of high-grade dysplasia should be confirmed by two pathologists before initiating radiofrequency ablation. The American Society for Gastrointestinal Endoscopy and the American Gastroenterological Association both recommend that a reading of high-grade dysplasia (HGD) should be confirmed by an experienced gastrointestinal pathologist. Two cohort studies found that reevaluation of HGD after an initial evaluation resulted in 40% to 53% of individuals receiving a lower-grade evaluation on repeat endoscopy, highlighting the need for confirmation by an expert center. Additionally for HGD, it is important to rule out adenocarcinoma; referral to an expert center that can conduct high-definition white-light endoscopy and other diagnostic techniques has been found to increase the rate of adenocarcinoma detection and proper referral for endoscopic mucosal resection.

There is considerable interobserver variability in the diagnosis of low-grade dysplasia (LGD), and the potential exists for overdiagnosis of LGD by nonexpert pathologists (overdiagnosis is due primarily to the difficulty in distinguishing inflammatory changes from low-grade dysplasia). There is literature evidence that expert GI pathologists will downgrade a substantial portion of biopsies that are initially read as low-grade dysplasia by nonexperts. As a result, it is ideal that two experts in GI pathology agree on the diagnosis to confirm low-grade dysplasia; this may result in greater than 75% of initial diagnoses of low-grade dysplasia being downgraded to nondysplasia. A review by a single expert GI pathologist will also result in a large number of low-grade dysplasia diagnoses being downgraded, although probably not as many as achieved using two expert pathologists.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good 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. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

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

3/3/2009: Policy added

04/27/2010: “Cryoablation” added to the policy title. Policy description updated regarding disease progression, dysplasia criteria, cryoablation, and devices. Policy statement revised to indicate that radiofrequency ablation may be considered medically necessary for high-grade dysplasia. Based on this revised policy statement, moved CPT code 43257 to the Covered table and added ICD-9 code 530.85 as a covered diagnosis. Radiofrequency ablation for low-grade dysplasia or Barrett’s esophagus in the absence of dysplasia is considered investigational. New policy statement added that cryoablation is considered investigational. FEP verbiage added to the Policy Exceptions section. Corrected the typo of CPT code 43288; correct code is 43228.

02/23/2011: Policy reviewed; no changes.

07/12/2012: The policy statement regarding low-grade dysplasia was changed from investigational to medically necessary as follows: Radiofrequency ablation may be considered medically necessary for treatment of Barrett’s esophagus with low-grade dysplasia, when the initial diagnosis of low-grade dysplasia is confirmed by a second pathologist who is an expert in GI [gastrointestinal] pathology. Policy guidelines updated regarding diagnosing low-grade dysplasia.

06/13/2013: Policy reviewed; no changes.

07/15/2014: Policy reviewed; description updated regarding Barrett's Esophagus and the Risk of Esophageal Carcinoma. Added "(see Policy Guidelines)" to the first policy statement. Policy statement on radiofrequency ablation for treatment of Barrett's esophagus with low-grade dysplasia revised to change "a second pathologist who is an expert in GI [gastrointestinal] pathology" to "2 physicians (see Policy Guidelines)." Third policy statement revised. It previously stated: Radiofrequency ablation is considered investigational as a treatment of Barrett's esophagus in the absence of dysplasia. Policy Guidelines updated regarding low-grade dysplasia.

08/18/2015: Medical policy revised for ICD-10.

11/11/2015: Policy description updated. First investigational policy statement updated to clarify that radiofrequency ablation is considered investigational for treatment of Barrett esophagus when the medically necessary criteria are not met, including but not limited to Barrett esophagus in the absence of dysplasia. Policy guidelines updated to add medically necessary and investigative definitions.

01/11/2016: Policy description updated regarding devices. Policy statements unchanged.

06/01/2016: Policy number A.2.01.80 added.

12/01/2016: Policy description updated. Policy statements unchanged.

01/04/2018: Policy description updated. Policy statements unchanged.

12/28/2018: Policy title updated to change "Barrett's Esophagus" to "Barrett Esophagus." Policy description updated regarding strategies for confirming patients with low-grade dysplasia. Policy statements unchanged.

05/15/2019: Code Reference section updated to add CPT codes 43229 and 43270 as investigational. Removed deleted CPT code 43228.

12/09/2019: Policy description revised to remove section regarding Barrett Esophagus and risk of esophageal carcinoma. Medically necessary statement regarding Barrett Esophagus with low-grade dysplasia revised to change "physicians" to "pathologists."

01/13/2021: Policy description updated regarding devices. Policy statements unchanged. Policy Guidelines updated regarding recommendations by the American Society for Gastrointestinal Endoscopy and the American Gastroenterological Association.

01/26/2022: Policy description and Policy Guidelines updated. Policy statements unchanged.

12/15/2022: Policy description updated regarding devices. Policy statements unchanged. Policy Guidelines updated.

12/13/2023: Policy description updated regarding Barrett Esophagus and the risk of esophageal carcinoma. Policy statements unchanged.

01/29/2025: Policy description updated regarding ablative techniques. Policy statements unchanged. Policy Guidelines updated.

SOURCE(S)

Blue Cross & Blue Shield Association Policy # 2.01.80

CODE REFERENCE

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

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

Investigational Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.