BlueCross and BlueShield of Montana Medical Policy/Codes
Endoscopic Radiofrequency Ablation or Cryoablation for Barretts Esophagus
Chapter: Surgery: Procedures
Current Effective Date: October 25, 2013
Original Effective Date: June 07, 2010
Publish Date: October 25, 2013
Revised Dates: April 28, 2011; August 31, 2012; September 30, 2013
Description

Barrett’s Esophagus and the Risk of Esophageal Carcinoma

The esophagus is normally lined by squamous epithelium.  Barrett’s esophagus 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 (GERD).  Barrett’s esophagus occurs in the distal esophagus, may be of any length, focal or circumferential, and can be visualized by the endoscopist as being a different color than the background squamous mucosa.  Confirmation of Barrett’s esophagus requires biopsy of the columnar epithelium and microscopic identification of intestinal metaplasia.

Intestinal metaplasia is a precursor to esophageal adenocarcinoma, and patients with Barrett’s esophagus are at a 40-fold increased risk for developing this disease compared to the general population.  Esophageal adenocarcinoma is thought to result from a stepwise accumulation of genetic abnormalities in the specialized epithelium, which results in the phenotypic expression of histologic features of low-grade dysplasia to high-grade dysplasia to carcinoma.  Most patients with nondysplastic Barrett’s esophagus do not progress past nondysplasia.  Nondysplastic Barrett’s esophagus progresses to high-grade dysplasia at a rate of 0.9% per patient, per year.   Progression of low-grade to high-grade dysplasia has been reported as 6-28%.  Once high-grade dysplasia is present, the risk of developing adenocarcinoma is 2–10% per patient, per year, and approximately 40% of patients diagnosed with high-grade dysplasia by biopsy are found to have associated carcinoma in the resection specimen.

Management of Barrett’s Esophagus

The current management of Barrett’s esophagus includes treatment of GERD, and surveillance endoscopy to detect progression to high-grade dysplasia or adenocarcinoma.  The finding of low-grade dysplasia typically warrants only follow-up and surveillance biopsies, whereas 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).  Mucosal ablation techniques that are available consist of one of several thermal (multipolar electrocoagulation [MPEC], argon plasma coagulation [APC], heater probe, Nd:YAG laser, KTP-YAG laser, diode laser, argon laser, and cryoablation) or nonthermal (5-aminolevulinic acid [5-ALA] and photofrin photodynamic therapy [PDT]) techniques.   

The HALO System from BARRX Medical, Inc. (Sunnyvale, Calif.) uses radiofrequency energy and consists of two components: an energy generator and an ablation catheter.  The generator provides rapid (i.e., less than one second) delivery of a predetermined amount of radiofrequency energy to the catheter.  Both the HALO90 and HALO360 are inserted into the esophagus with an endoscope, using standard endoscopic techniques.  The HALO90 catheter is plate-based and used for focal ablation of areas of Barrett’s esophagus up to 3 cm.  The HALO360 uses a balloon catheter that is sized to fit the individual esophagus, and is inflated to allow for circumferential ablation.    The ablation with radiofrequency affects only the most superficial layer of the esophagus (the mucosa), leaving the underlying tissues unharmed.  Efficacy measures of the procedure include eradication of intestinal metaplasia without leaving behind microscopic (or “buried”) foci and post-ablation regrowth of the normal squamous epithelium.

The CryoSpray Ablation™ System (formerly the SprayGenix™ Cryo Ablation System, CSA Medical, Inc.) uses a low-pressure spray for spraying liquid nitrogen through an upper endoscope.  Cryotherapy allows for treatment of uneven surfaces, however, disadvantages include the uneven application inherent in spraying the cryogen.  Treating high-grade dysplasia or mucosal cancer solely with ablative techniques risks under treating the approximately 10% of patients who have undetected submucosal cancer, in whom esophagectomy would have been required.

Regulatory Status

The HALO360 received U.S.  Food and Drug Administration (FDA) 510(k) clearance for marketing in 2005 and the HALO90 in 2006.  The FDA-labeled indications are for use in coagulation of bleeding and nonbleeding sites in the gastrointestinal tract, and include the treatment of Barrett’s esophagus.  The CryoSpray Ablation™ System received FDA 510(k) marketing clearance in December 2007 for use as a “cryosurgical tool for destruction of unwanted tissue in the field of general surgery, specifically for endoscopic applications.”

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

Radiofrequency ablation may be considered medically necessary for Barrett’s esophagus with low-grade or high-grade dysplasia when confirmed by two pathologists prior to ablation.

Note:  Radiofrequency ablation for Barrett’s esophagus with high-grade dysplasia may be used in combination with endoscopic mucosal resection of nodular/visible lesions.

Radiofrequency ablation is considered experimental, investigational and unproven for Barrett’s esophagus without dysplasia.

Cryoablation is considered experimental, investigational and unproven for Barrett’s esophagus, with or without dysplasia.

Rationale

Radiofrequency Ablation (RFA)

One randomized trial using RFA in Barrett’s esophagus with dysplasia has been published.  A randomized, multicenter, sham-controlled trial assigned 127 patients with dysplastic Barrett’s esophagus in a 2:1 ratio to receive RFA or a sham procedure.  The groups were randomized according to the grade of dysplasia (low-grade [n=64] or high-grade [n=63]) and length of the Barrett’s esophagus (<4 cm or 4-8 cm).  Primary outcomes were the proportion of patients with low-grade or high-grade dysplasia who had complete eradication of dysplasia at 12 months and the proportion of all patients who had complete eradication of intestinal metaplasia at 12 months. Secondary outcomes included the proportion of patients who had progression of dysplasia, including low to high-grade dysplasia or to cancer, and the progression of high-grade dysplasia to cancer.  Among patients in the RFA group, the entire segment of Barrett’s esophagus was ablated.  Patients in the RFA group could receive up to 4 ablation sessions, performed at baseline, and at 2, 4, and 9 months.  In patients with low-grade dysplasia, the dysplasia was completely eradicated in 90.5% of those in the RFA group, compared with 22.7% of those in the control group (p<0.001).  In patients with high-grade dysplasia, complete eradication occurred in 81% of the ablation group versus 19% in the control group (p<0.001).  Overall, complete eradication of intestinal metaplasia was 77.4% in the ablation group compared with 2.3% of the control group (p<0.001) Patients who did not receive RFA were more likely to have disease progression (16.3%) than those that received RFA (3.6%; p=0.03).  Among patients with high-grade dysplasia, 19% of those in the control group progressed to cancer, versus 2.4% progression to cancer in the RFA group (p=0.04).  Three serious adverse events occurred in the RFA group, including one episode of upper gastrointestinal hemorrhage, which was treated endoscopically, one overnight hospitalization for new-onset chest pain 8 days after RFA and one night of hospitalization for an episode of chest discomfort and nausea immediately after RFA.  No adverse events were observed in the control group.  No esophageal perforations or procedure-related deaths occurred.  Among patients in the RFA group, esophageal stricture developed in five patients (6%), all of which were successfully dilated endoscopically.  To date, the remainder of the studies using RFA for Barrett’s esophagus have been conducted to investigate the safety and efficacy of this technique, and have consisted mainly of small numbers of patients with relatively short follow-up.

Ganz et al. reported registry data from 142 patients with Barrett’s esophagus who underwent circumferential ablation for high-grade dysplasia.  The patients were from 16 academic and community centers, treated between 2004 and 2007, and ranged in age from 59–75 years (median age, 66 years).  Median length of Barrett’s esophagus segment was 6 cm (range, 3–8 cm).  No adverse events were reported.  Ninety-two of the patients had at least one follow-up biopsy (median follow-up: 12 months; range: 8–15 months).  Outcome measures were defined as histologic complete response (CR), defined as all biopsy specimens negative for high-grade dysplasia, any dysplasia, or intestinal metaplasia.  CR was achieved for high-grade dysplasia in 90.2%, any dysplasia in 80.4%, and intestinal metaplasia in 54.3%.

Sharma et al. reported their experience with 100 patients with Barrett’s esophagus without dysplasia, to investigate the safety and efficacy of balloon-based circumferential radiofrequency ablation.  Patient age ranged from 18–75 years (median: 55.7 years).  This prospective study involved 8 U.S. centers, between 2003 and 2005.  Sixty-nine of 70 patients who underwent mucosal ablation were available for follow-up.  Efficacy was evaluated with follow-up endoscopy and biopsy at 1, 3, 6, and 12 months.  If patients had Barrett’s esophagus present at month 1 or 3, repeat ablation was performed.  CR was defined as all biopsy specimens negative for Barrett’s esophagus at 12 months and was achieved in 70% of patients.  The authors reported an extension of this trial, evaluating 62 of the original patients, 61 of which were available for 30-month follow-up.  Fifty-nine of the 62 patients had to undergo additional focal ablation after the 12-month follow-up.  CR was achieved in 60 (98%) of the patients at the end of the 30 months.

Pouw et al. reported their experience with 44 patients with Barrett’s esophagus less than 12 cm in length with either high-grade dysplasia or early carcinoma.  Prior to ablation, visible lesions and early carcinoma were endoscopically removed.  After ablation, complete histological eradication of all dysplasia and intestinal metaplasia was achieved in 43 patients (98%).  No dysplasia had recurred after 21 months of follow-up (range: 10–27 months). 

Roorda et al. reported their experience using radiofrequency ablation in 13 patients with Barrett’s esophagus (three with high-grade dysplasia, four with low-grade dysplasia, and six with nondysplastic intestinal metaplasia).  Mean baseline Barrett’s esophagus length was 6 cm (range: 2–12 cm).  Complete eradication of Barrett’s esophagus was achieved in 6 of 13 patients (46%).  Complete elimination of dysplasia was achieved in five of seven (71%) patients.

Hernandez et al. reported on a pilot series in 10 patients with Barrett’s esophagus, followed up for at least 12 months.  Seven patients had Barrett’s esophagus without dysplasia, two with low-grade dysplasia, and one with high-grade dysplasia.  Complete eradication of Barrett’s esophagus was achieved in seven patients and partial eradication in three.

2010 Update

HALO System

Reports of the efficacy of the HALO system in ablating Barrett’s esophagus have been as high as 70% (comparable to alternative methods of ablation [e.g., APC and MPEC]), and even higher in some reports.  The incidence of leaving behind “buried” foci of intestinal metaplasia has been reported to be 20–44% with APC and 7% with MPEC; reports using the HALO system have been 0%.  Another potential advantage to the HALO system is that because it is automated, it eliminates operator-dependent error that may be seen with APC and MPEC.

Cryoablation

Published efficacy data for cryoablation in Barrett’s esophagus are limited.  Johnston and colleagues conducted a prospective, single-center pilot study in 11 men with Barrett’s esophagus and degrees of dysplasia ranging from none to multifocal high-grade dysplasia.  The mean length of Barrett’s was 4.6 cm (range: 1–8 cm).  After six months’ follow-up, complete histologic eradication of Barrett’s esophagus was achieved in seven of the nine patients (78%) completing the protocol.  An open-label, single-center, prospective, nonrandomized cohort study assessed the safety of cryoablation as a treatment option for Barrett’s esophagus with high-grade dysplasia or early cancer (intramucosal carcinoma).  Thirty patients who were either deemed high-risk surgical candidates or who refused esophagectomy underwent cryoablation.  Twenty-seven patients (90%) had downgrading of pathology stage after treatment.  After a median follow-up period of 12 months, elimination of cancer or downgrading of high-grade dysplasia was 68% for high-grade dysplasia and 80% for intramucosal cancer.

American College of Gastroenterology

According to guidelines from the American College of Gastroenterology, “…high-grade dysplasia is associated with a 30% risk of cancer development.  Treatment needs to be individualized with options of careful intensive surveillance, endoscopic ablation therapy, and surgical resection being presented to the patient based on their appropriateness for these options and the expertise available to provide them.  At the current time, it appears as if surveillance with intensive biopsies, endoscopic ablative techniques (most likely a combination of techniques), or esophagectomy may produce similar outcomes in retrospective cohort studies from expert centers.  The selection of which of these therapies must be individualized and will depend on the expertise available in the patient’s community, the patient’s preferences, and the gastroenterologist’s own experience (Grade B recommendation)”. 

The Society of Thoracic Surgeons Practice Guideline Series: Guidelines for the Management of Barrett’s Esophagus with High-Grade Dysplasi

The 2009 guidelines for the management of Barrett’s esophagus, note that RFA may be considered to treat patients with Barrett’s metaplasia, and that it may be effective for ablation of high-grade dysplasia, but that further trials are needed before this can be recommended in preference to currently available ablative therapies.  Specific to pathologist interpretation of high-grade dysplasia the guidelines note the following as a Class I Recommendation, “Histological evaluation of high-grade dysplasia should be undertaken by two pathologists experienced in interpreting esophageal metaplasia.

National Comprehensive Cancer Network Guidelines

The 2010 National Comprehensive Cancer Network clinical practice guidelines for esophageal cancer state that esophageal cancer stage Tis (carcinoma in situ) or T1a (intramucosal invasion) may be treated primarily with endoscopic mucosal resection, esophagectomy, or ablation; RAF is not specifically addressed and the guidelines state that among the methods of mucosal ablation, photodynamic therapy is superior for achieving ablation of metaplastic and dysplastic epithelium as well as for obviating the need for further interventions. 

2009 National Cancer Institute

The 2009 Clinical Trials Database (PDQ®) of the U.S.  National Institutes of Health ClinicalTrials.gov registry identified a phase II/III trial currently recruiting participants with Barrett’s esophagus and gastroesophageal reflux disease.  The aim of the study is to evaluate the long-term efficacy of evidence-based diagnostic and therapeutic algorithms and techniques (such as radiofrequency).  Estimated enrollment is 100 patients, with an estimated study completion date of August 2017 (NCT00513331).

Conclusion

A search of peer reviewed literature was conducted through February 2010.  Radiofrequency ablation of high-grade dysplasia in Barrett’s esophagus has been shown to be at least as effective in eradicating high-grade dysplasia as other ablative techniques with a lower progression rate to cancer, and may be considered as an alternative to esophagectomy.  More data are required concerning the use of RFA for the eradication of low-grade dysplasia and nondysplastic Barrett’s esophagus.  Longer follow-up is needed to show that eradication will persist, and that the benefits will outweigh potential complications in these patients who show a lower rate of progression to adenocarcinoma than those with high-grade dysplasia.  Data for the efficacy of cryoablation of Barrett’s esophagus with or without dysplasia are limited.  The studies consist of small numbers of patients with short-term follow-up.   

2011 Update

RFA for Low-Grade Dysplasia

Review of literature through October 2011 identified a 2011 Position Statement from the American Gastroenterological Association (AGA) addressing the management of Barrett’s esophagus.  Specific to low-grade dysplasia, the AGA recommends that RFA should be considered a therapeutic option for treatment of patients with confirmed low-grade dysplasia in Barrett’s esophagus.  In addition the AGA notes “RFA therapy for patients with low-grade dysplasia lead to reversion to normal-appearing squamous epithelium in >90% of cases with quality of evidence documented as high.

Shaheen et al. performed a follow-up of the subjects from the AIM Dysplasia trial to an average of 3.05 years.  The authors note that this study demonstrated that a high percentage of subjects with both low-grade and high-grade dysplasia retain complete eradication of dysplasia and intestinal metaplasia after treatment.  Progression of disease was rare in subjects who underwent RFA treatment, and the rate of progression to EAC in this dysplastic cohort was 0.55%.  There was no procedure- or cancer-related mortality.  The main adverse side effect was stricture occurrence, which occurred in 7.6% of subjects and correctable with dilation.

RFA and Cryoablation for Nondysplasia (without dysplasia)

The 2011 AGA Position Statement notes there is no data from controlled trials showing that endoscopic eradication therapy, including RFA and cryotherapy, is more effective at reducing cancer risk or more cost-effective than long-term endoscopic surveillance in patients with Barrett’s esophagus in the absence of dysplasia.  Quality of evidence for this documentation indication is documented as low.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes
42.33, 211.0, 530.85
ICD-10 Codes
K22.711, K22.719, 0D518ZZ, 0D528ZZ, 0D538ZZ, 0D548ZZ, 0D558ZZ 
Procedural Codes: 43228, 43257, 43258, 43499
References
  1. Overholt, B.F., Lightdale, C.J., et al.   Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial.  Gastrointestinal Endoscopy (2005) 62(4):488-98. 
  2. Johnston MH, Eastone JA, Horwhat JD et al.  Cryoablation of Barrett’s esophagus: a pilot study.  Gastrointest Endosc 2005; 62(6):842-8.
  3. Sharma, V.K., Wang, K.K., et al.   Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus: 1-year follow-up of 100 patients.  Gastrointestinal Endoscopy (2007) 65(2):185-95.
  4. Roorda, A.K., Marcus, S.N., et al.  Early experience with radiofrequency energy ablation therapy for Barrett’s esophagus with and without dysplasia.  Diseases of the Esophagus (2007) 20(6):516-22. 
  5. Pech O, Ell C.  Endoscopic therapy of Barrett’s esophagus.  Curr Opin Gastroenterol 2009; 25(5): 405-11/
  6. Ell C, May A, Pech O et al.  Curative endoscopic resection of early esophageal adenocarcinoma (Barrett’s cancer).  Gastrointest Endosc 2007; 65(1):3-10.
  7. Ganz, R.A., Overholt, B.F., et al.   Circumferential ablation of Barrett’s esophagus that contains high-grade dysplasia: a U.S.  multicenter registry.  Gastrointestinal Endoscopy (2008) 68(1):35-40. 
  8. U.S.  Food and Drug Administration.  510(k) Premarket Notification Database.  BARRX MODELS HALO360 AND HALO360+ COAGULATION CAT.  No.  K080557.  April 2, 2008.  Available at <www.accessdata.fda.gov>.  (accessed - November 2008). 
  9. Fleischer, D.E., Overholt, B.F., et al.   Endoscopic ablation of Barrett’s esophagus: a multicenter study with 2.5-year follow-up.  Gastrointestinal Endoscopy (2008) 68(5):867-76. 
  10. Pouw, R.E., Gondrie, J.J., et al.   Eradication of Barrett esophagus with early neoplasia by radiofrequency ablation, with or without endoscopic resection.  Journal of Gastrointestinal Surgery (2008) 12(10):1636-7. 
  11. Hernandez, J.C., Reicher, S., et al.  Pilot series of radiofrequency ablation of Barrett's esophagus with or without neoplasia.  Endoscopy (2008) 40(5):388-92. 
  12. Wang, K.K., Sampliner, R.E.   Practice Parameters Committee of the American College of Gastroenterology.  Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus.  American Journal of Gastroenterology (2008) 103(3):788-97.  Available at www.acg.gi.org (accessed - November 2008). 
  13. Esophageal Cancer.  National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, v.1.2009; Available at www.nccn.org (accessed – November 2008).
  14. Shaheen, N., Sharma, P, et al.   Radiofrequency Ablation in Barrett’s Esophagus with Dysplasia
  15. New England Journal of Medicine.   May 28 2009: 360:22, 2277-2288.
  16. U.S. Food and Drug Administration.  510(k) Premarket Notification Database.  CryoSpray Ablation System.  No.  K072651.  December 7, 2007.  Available online at: http://www.accessdata.fda.gov    Last accessed December 2009.
  17. Dumot JA, Vargo JJ, Falk GW et al.  An open-label, prospective trial of cryospray ablation for Barrett’s esophagus high-grade dysplasia and early esophageal cancer in high-risk patients.  Gastrointest Endosc 2009; 70(4):635-44.
  18. Fernando HC, Murthy SC, Hofstetter W et al.  The Society of Thoracic Surgeons practice guideline series: guidelines for the management of Barrett’s esophagus with high-grade dysplasia.  Ann Thorac Surg 2009; 87(6):1993-2002.
  19. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology.  Esophageal Cancer (v.1.2010); available online at http://www.nccn.org .
  20. Endoscopic Radiofrequency Ablation for Barrett’s Esophagus.   Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2009 December) Medicine 2.01.80.
  21. American Gastorenterological Association Medical Position Statement on the Management of Barrett’s Esophagus.  Gastroenterology 2011; 140:1084-1091
  22. Shaheen, N., Overholt, B., et al.  Durability of Radiofrequency Ablation in Barrett’s Esophagus with Dysplasia.  Gastroenterology 2011; 141:460 -468.
History
April 2011  Policy statement revised to indicate that RF ablation may be considered medically necessary for high-grade dysplasia. New policy statement added that cryoablation is considered investigational. Cryoablation added to the policy title.  References and rationale updated.
August 2012  Policy updated with literature search. Policy statement updated to include RFA 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 pathology, as medically necessary. References 1, 2, 9, 10, 16, 18, 19, 30, 31 added; reference 32 updated 
October 2013 Policy formatting and language revised.  Policy statement unchanged. 
BCBSMT Home
®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.
CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
Endoscopic Radiofrequency Ablation or Cryoablation for Barretts Esophagus