Medical Policy

Policy Num:      02.001.034
Policy Name:    Endoscopic Radiofrequency Ablation or Cryoablation for Barrett Esophagus
Policy ID:          [02.001.034]  [Ac / B / M+ / P+]  [2.01.80]

Last Review:       December 02, 2024
Next Review:       December 20, 2025
 

Related Policies:

02.001.074 - Confocal Laser Endomicroscopy
08.001.008 - Oncologic Applications of Photodynamic Therapy,Including Barrett Esophagus

                Endoscopic Radiofrequency Ablation or Cryoablation for Barrett Esophagus

Summary

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.

Summary of Evidence

For individuals who have Barrett esophagus (BE) with high-grade dysplasia (HGD) who receive endoscopic radiofrequency ablation (RFA) , the evidence includes a randomized controlled trial (RCT) comparing radical endoscopic resection with focal endoscopic resection followed by RFA, 1 RCT comparing RFA with surveillance alone, and a systematic review evaluating RCTs and a number of observational studies, some of which compared RFA with other endoscopic treatment modalities. Relevant outcomes are change in disease status, morbid events, and treatment-related morbidity and mortality. The available evidence has shown that using RFA to treat BE with HGD is at least as effective in eradicating HGD as other techniques, with a lower progression rate to cancer, and may be considered an alternative to esophagectomy. Evidence from at least 1 RCT has demonstrated higher rates of eradication than surveillance alone. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have BE with low-grade dysplasia (LGD) who receive endoscopic RFA, the evidence includes at least 3 RCTs comparing RFA with surveillance alone, a number of observational studies, and systematic reviews of these studies. Relevant outcomes are change in disease status, morbid events, and treatment-related morbidity and mortality. For patients with confirmed LGD, evidence suggests that RFA reduces progression to HGD and adenocarcinoma. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have BE without dysplasia who receive endoscopic RFA, the evidence includes single-arm studies reporting outcomes after RFA. Relevant outcomes are change in disease status, morbid events, and treatment-related morbidity and mortality. The available studies have suggested that nondysplastic metaplasia can be eradicated by RFA. However, the risk-benefit ratio and the net effect of RFA on health outcomes are unknown. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have BE with or without dysplasia who receive endoscopic cryoablation, the evidence includes noncomparative studies and systematic reviews of those studies reporting outcomes after cryoablation. Relevant outcomes include change in disease status, morbid events, and treatment-related morbidity and mortality. These studies have generally demonstrated high rates of eradication of dysplasia. Recent observational studies comparing RFA with cryoablation show similar outcomes. However, there are no RCTs comparing cryoablation with surgical care or RFA. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

Not applicable.

Objective

The objective of this evidence review is to determine whether the use of endoscopic radiofrequency ablation, with or without endomucosal resection if indicated, or endoscopic cryoablation improves the net health outcome for individuals who have Barrett esophagus.

Policy Statements

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

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 section).

Radiofrequency ablation is considered investigational for the treatment of Barrett esophagus when 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 Guidelines

Radiofrequency ablation for Barrett esophagus with high-grade dysplasia (HGD) may be used in combination with endoscopic mucosal resection (EMR) of nodular or visible lesions. The diagnosis of HGD should be confirmed by 2 pathologists before initiating radiofrequency ablation. The American Society for Gastrointestinal Endoscopy and the American Gastroenterological Association both recommend that a reading of HGD should be confirmed by an experienced gastrointestinal pathologist[Wani et. al., 2018, PMID 29397943; Sharma et. al. 2020, PMID 31730766]. 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[Sangle et. al., 2015, PMID 25676554; Verbeek et. al, 2014; PMID 24388501]. 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 EMR[Cameron et. al., 2014; PMIT 24929493].

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 LGD). There is evidence in the literature that expert gastrointestinal pathologists will downgrade a substantial portion of biopsies that are initially read as LGD by nonexperts (Curvers et al [2010], PMID 20461069; Kerkhof et al [2007], PMID 17543082). As a result, it is ideal that 2 experts in gastrointestinal pathology agree on the diagnosis to confirm LGD; this may result in greater than 75% of initial diagnoses of LGD being downgraded to nondysplasia (Curvers et al [2010]). A review by a single expert gastrointestinal pathologist will also result in a large number of LGD diagnoses being downgraded, although probably not as many as achieved using 2 expert pathologists (Kerkhof et al, 2007).

Coding

See the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

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 8000 patients with a mean duration of follow-up of 7 years (range, 1 to 20 years).^1, 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%.^2, Detection of LGD on index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years, and the incidence rate among patients without dysplasia was 1.0 case per 1000 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.^3,4, 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.^5,

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.^6, Kerkhof et al (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.^7, Curvers et al (2010) tested this hypothesis in 147 patients with BE who were given an initial diagnosis of LGD.^8, 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 et al (2014), which required confirmation of LGD by a central expert panel following initial diagnosis by a local pathologist.^9, 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 et al (2015) who reported on 293 BE cases with LGD diagnosed over an 11-year period and submitted for expert panel review.^10, 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 HGD or adenocarcinoma. The finding of HGD 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 2007 study provided long-term results for EMR in 100 consecutive patients with early Barrett-associated adenocarcinoma (limited to the mucosa).^11, The 5-year overall survival was 98% and, after a mean of 36.7 months, metachronous lesions were observed in 11% of patients. In a review by Pech and Ell (2009), the authors 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%.^12,

Ablative Techniques

Available mucosal ablation techniques 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, cryoablation) or nonthermal (5-aminolevulinic acid, photodynamic therapy) techniques. In a randomized phase 3 trial reported by Overholt et al (2005), photodynamic therapy was shown to decrease significantly the risk of adenocarcinoma in BE.^13, (Photodynamic therapy for BE is discussed in evidence review 8.01.06.)

The CryoSpray Ablation system uses a low-pressure spray for applying liquid nitrogen through an upper endoscope. Cryotherapy allows for the treatment of uneven surfaces; however, a disadvantage of the treatment is the uneven application inherent in spraying the cryogen.

The HALO system uses radiofrequency energy and consists of 2 components: an energy generator and an ablation catheter. The generator provides rapid (ie, <1 second) delivery of a predetermined amount of radiofrequency energy to the catheter. The HALO90 or the HALO360 is 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 BE up to 3 cm. HALO360 uses a balloon catheter that is sized to fit the individual’s esophagus and is inflated to allow for circumferential ablation.

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 the postablation regrowth of the normal squamous epithelium. (Note: The eradication of intestinal metaplasia does not leave behind microscopic foci). Reports of the efficacy of the HALO system in ablating BE have been as high as 70% (comparable with alternative methods of ablation [eg, APC, 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%.^14, Another potential advantage of the HALO system is that it is an automated process that eliminates operator-dependent error, which may be seen with APC or MPEC.

The risk of treating HGD 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.^12,

Regulatory Status

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.^15, The FDA labeled indications are for use in coagulation of bleeding and nonbleeding sites in the gastrointestinal tract and include the treatment of BE. Other focal ablation devices from Barrx include the Barrx™ 60 RFA Focal Catheter, the Barrx™ Ultra Long RFA Focal Catheter, the Barrx™ Channel RFA Endoscopic Catheter.

FDA product code: GEI.

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.”^16, 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.^17,The next-generation C2 CryoBalloon Ablation System was introduced in 2018.^18,

FDA product code: GEH.

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.”^19,

Rationale

This evidence review was created in December 2008 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through September 19, 2024.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

Radiofrequency Ablation for Barrett Esophagus With High-Grade Dysplasia

Clinical Context and Therapy Purpose

In patients diagnosed with BE with HGD, the risk of progression to cancer is relatively high, and esophageal adenocarcinoma is associated with high morbidity and a 5-year survival rate of up to 13%. ^20,21, Therefore, intervention with esophagectomy or RFA may be strongly indicated.

The purpose of endoscopic RFA in patients who have BE with HGD is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICOs were used to select literature to inform this review.

Populations

The relevant population of interest are patients with BE with HGD.

Interventions

The therapy being considered is endoscopic RFA. Endoscopic RFA is administered in an outpatient care setting by gastroenterologists.

Comparators

The following therapies and practices are currently being used to treat BE: esophagectomy, endoscopic mucosal resection, and surveillance.Esophagectomy is an inpatient procedure performed in a tertiary care facility; endoscopic mucosal resection is an outpatient procedure performed in a tertiary care facility or specialized clinic.

Outcome

The general outcomes of interest are symptoms (eg, pain), functional outcomes (including swallowing), and cancer-specific survival.

Beneficial outcomes include reductions in esophageal dysplasia and mortality.

Harmful outcomes include damage to the esophagus resulting in difficulty swallowing.

Morbidity from treatment would be assessed within 30 days after the procedure. Overall survival (OS) and disease-specific survival would be measured at three to five years.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Systematic Reviews

Chadwick et al (2014) reported on a systematic review that compared RFA with complete EMR for the treatment of BE.^22, Twenty studies (22 articles) were reviewed, including 2 RCTs, 10 cohort studies on EMR, and 8 cohort studies on RFA. The only study that compared RFA with EMR was an RCT by van Vilsteren et al (2011)^23,; the other RCT was by Shaheen et al (2009, 2011; see below).^24,25, The studies were heterogeneous in design. A total of 1087 (532 EMR, 555 RFA) patients with HGD or intramucosal carcinoma were included in the studies reviewed. The median number of resections or RFA sessions required for the eradication of BE was 2. Complete EMR and RFA eradicated BE dysplasia in 95% and 92% of patients, respectively. Eradication was maintained in 95% of EMR patients at a median follow-up of 23 months and in 94% of RFA patients at a median follow-up of 21 months. Fewer RFA patients experienced short-term adverse events (2.5%) than those who received complete EMR (12%). Esophageal strictures requiring additional treatment occurred in 4% of RFA patients and 38% of complete endoscopic resection patients.

Randomized Controlled Trials

RFA may be used alongside focal endoscopic resection. In the intention-to-treat analysis of a prospective interventional study by Phoa et al (2016) that included 132 subjects with BE and HGD or early cancer treated with endoscopic resection followed by RFA, complete eradication of neoplasia and complete eradication of intestinal metaplasia occurred in 92% and 87% of subjects, respectively.^26, At a median follow-up of 27 months, neoplasia and intestinal metaplasia had recurred in 4% and 8% of subjects, respectively.

Van Vilsteren et al (2011) reported on the results of a multicenter randomized trial that compared the safety of stepwise radical endoscopic resection (SRER) with focal EMR followed by RFA for complete eradication of BE 5 cm or less with HGD or early cancer.^23, Patients in the SRER group underwent a piecemeal EMR of 50% of BE followed by serial EMR. Patients in the EMR plus RFA group underwent focal EMR for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (4-quadrant/2 cm BE) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histologic response for neoplasia; and complete histologic response for intestinal metaplasia (CR-IM). Complete histologic response for neoplasia was achieved in 25 (100%) of 25 SRER patients and in 21 (96%) of 22 patients receiving EMR plus RFA. CR-IM was achieved in 23 (92%) SRER patients and 21 (96%) patients receiving EMR plus RFA. The stenosis rate was significantly higher with SRER (88%) than with EMR plus RFA (14%; p<.001), resulting in more therapeutic sessions in SRER (6 vs. 3; p<.001) due to dilations. After a median follow-up of 24 months, 1 SRER patient had a recurrence of early cancer, requiring endoscopic resection. This trial confirmed that both techniques achieved comparably high rates of CR-IM and complete histologic response for neoplasia but found that SRER was associated with more complications and therapeutic sessions.

The randomized multicenter, sham-controlled trial by Shaheen et al (2009) compared RFA with surveillance alone in patients with BE and dysplasia.^24, RFA was successful in eradicating HGD, with complete eradication at 12 months achieved in 81% of the ablation group versus 19% in the control group (p<.001). This trial also confirmed a high-risk of progression to cancer in patients with HGD and established that this progression was significantly reduced in patients treated with RFA. Among 63 patients with HGD in the trial, 19% in the control group progressed to cancer versus 2.4% in the RFA group (p=.04). This represented a nearly 90% relative risk reduction for progression to cancer (relative risk, 0.1; 95% confidence interval [CI], 0.01 to 1.0; p=.04), and a number needed to treat of 6.0 to prevent 1 case of cancer over a 1-year period.

Longer-term follow-up at 2 to 3 years reported that complete eradication of dysplasia was maintained in most participants with initial HGD.^25, For 54 patients with HGD available for follow-up, all dysplasia was eradicated in 50 (93%) of 54, and all intestinal metaplasia was eradicated in 48 (89%) of 54. After 3 years, dysplasia was eradicated in 55 (98%) of 56 subjects, and all intestinal metaplasia was eradicated in 51 (91%) of 56 subjects. More than 75% of patients with HGD remained free of intestinal metaplasia with a follow-up of longer than 3 years, with no additional therapy.

Section Summary: RFA for BE With HGD

For patients who have BE with HGD, there is a relatively high-risk of progression to cancer, and interventions to prevent progression are warranted. RFA results in high rates of complete eradication of dysplasia that is durable for at least two years. One RCT demonstrated that, following RFA, the progression from HGD to cancer is reduced by approximately 90%, with rates of esophageal strictures of 6%.

For individuals who have Barrett esophagus (BE) with high-grade dysplasia (HGD)  who receive endoscopic RFA, the evidence includes an RCT comparing radical endoscopic resection with focal endoscopic resection followed by RFA, an RCT comparing RFA with surveillance alone, and a number of observational studies, some of which compared RFA with other endoscopic treatment modalities. The relevant outcomes are OS, change in disease status, morbid events, and treatment-related morbidity and mortality. The available evidence has shown that using RFA to treat BE with HGD is at least as effective in eradicating HGD as other ablative techniques, with a lower progression rate to cancer, and may be considered an alternative to esophagectomy. Evidence from at least one RCT has demonstrated higher rates of eradication than surveillance alone. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 2

RFA for BE With Low-Grade Dysplasia

Clinical Context and Therapy Purpose

The purpose of endoscopic RFA in patients who have BE with LGD is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICOs were used to select literature to inform this review.

Populations

The relevant population of interest are patients with BE with LGD.

Interventions

The therapy being considered is endoscopic RFA. Endoscopic RFA is administered in an outpatient care setting by gastroenterologists.

Comparators

The following practice is currently being used to treat BE with LGD: surveillance by gastroenterologists.

Outcome

The general outcomes of interest are symptoms (eg, pain), functional outcomes (including swallowing), and cancer-specific survival.

Beneficial outcomes include reductions in esophageal dysplasia and mortality.

Harmful outcomes include damage to the esophagus resulting in difficulty swallowing.

Morbidity would be assessed within 30 days after the procedure. Conversion to HGD would be measured at two to five years.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Systematic Reviews

Wang et al (2022) performed a meta-analysis of 3 RCTs (N=282) comparing RFA with surveillance in patients with LGD.^27, Nearly 90% of the patients enrolled were male; other demographic information was not reported. The primary outcome was risk of progression to HGD or esophageal adenocarcinoma. Compared with endoscopic surveillance, RFA was associated with lower odds of progression to either HGD or esophageal adenocarcinoma (risk ratio [RR], 0.25; 95% CI, 0.07 to 0.93; p=.04).The findings had moderate heterogeneity (I²=55%), and the risk of bias was considered low. When analyzed separately, the risk of progression to HGD was significantly reduced with RFA (RR, 0.25; 95% CI, 0.07 to 0.71; p=.01; I²=15%); however, the results for progression to esophageal adenocarcinoma were not significant (RR, 0.56; 95% CI, 0.05 to 6.76; p=.65).

Klair et al (2021) performed a systematic review and meta-analysis of comparative studies of RFA versus endoscopic surveillance in patients with BE with LGD.^28, The primary outcome was risk of progression to HGD or esophageal adenocarcinoma. The meta-analysis included 4 studies (N=543), including 2 retrospective studies and 2 RCTs. Compared with endoscopic surveillance, RFA was associated with lower odds of progression to either HGD or esophageal adenocarcinoma (odds ratio [OR], 0.17; 95% CI, 0.04 to 0.65). Individually, the progression to HGD maintained significance compared with endoscopic surveillance (OR, 0.23; 95% CI, 0.08 to 0.61), while progression to adenocarcinoma was numerically lower (OR, 0.44; 95% CI, 0.17 to 1.16). However, the findings indicated moderate heterogeneity (I²=0.63) and evidence of publication bias.

In their meta-analysis, Pandey et al (2018) evaluated both RCTs and observational studies to determine the efficacy of RFA in treating BE with LGD compared with surveillance.^29, The 8 studies in the meta-analysis included 619 patients followed up for a median of 26 months. The overall pooled rate of complete eradication of intestinal metaplasia after RFA was 88.17% (95% CI, 88.13% to 88.20%; p<.001); the rate of complete eradication of dysplasia was 96.69% (95% CI, 96.67% to 96.71%; p<.001). Compared with surveillance, the rates of progression to HGD or cancer were significantly lower with RFA (OR, 0.07; 95% CI, 0.02 to 0.22). The pooled recurrence rate of intestinal metaplasia was 5.6% (95% CI, 5.57% to 5.63%; p<.001) and 9.66% (95% CI, 9.61% to 9.71%; p<.001) for dysplasia. Although the analysis was limited by its inclusion of observational cohort studies and the sample sizes of patients receiving RFA were all less than 100 patients, all studies supported the use of RFA for LGD BE. The authors concluded that RFA is safe and effective for eradicating intestinal metaplasia and dysplasia and reducing progression from LGD to HGD or cancer in the short term. Longer-term outcomes, however, warrant further research.

Section Summary: Radiofrequency Ablation for Barrett Esophagus With Low-Grade Dysplasia

The risk of progression from LGD to cancer is not well-defined, with highly variable rates reported in the published literature. Evidence from randomized and nonrandomized studies has established that RFA can achieve complete eradication of dysplasia in patients with LGD that is durable for at least 2 years. Combined rates of progression to HGD or esophageal adenocarcinoma are lower in patients with LGD treated with RFA compared with surveillance..

For individuals who have  BE with low-grade dysplasia (LGD) who receive endoscopic RFA, the evidence includes at least two RCTs comparing RFA with surveillance alone, a number of observational studies, and systematic reviews of these studies. The relevant outcomes are OS, change in disease status, morbid events, and treatment-related morbidity and mortality. For patients with confirmed LGD, evidence from an RCT has suggested that RFA reduces progression to HGD and adenocarcinoma. Challenges exist in differentiating between nondysplastic BE and BE with LGD; making the correct diagnosis has important implications for LGD treatment decisions. One of the available RCTs required that LGD be confirmed by an expert panel, which supports the use of having a gastrointestinal pathologist confirm LGD before treatment of BE with LGD can begin. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 3

RFA for BE Without Dysplasia

Clinical Context and Therapy Purpose

The purpose of endoscopic RFA in patients who have BE without dysplasia is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICOs were used to select literature to inform this review.

Populations

The relevant population of interest are patients with BE without dysplasia.

Interventions

The therapy being considered is endoscopic RFA. Endoscopic RFA is administered in an outpatient care setting by gastroenterologists.

Comparators

The following practice is currently being used to treat BE without dysplasia: surveillance by gastroenterologists.

Outcome

The general outcomes of interest are symptoms (eg, pain), functional outcomes (including swallowing), and cancer-specific survival.

Beneficial outcomes include reductions in mortality.

Harmful outcomes include damage to the esophagus resulting in difficulty swallowing.

Morbidity would be assessed within 30 days after the procedure. Conversion to dysplasia would be measured at two to five years.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Nonrandomized Trials

No RCTs were identified that evaluated RFA treatment of BE without dysplasia. The evidence on this issue consists of single-arm trials that have reported outcomes of RFA. There is no high-quality evidence on the comparative efficacy of RFA versus surveillance alone. Progression to cancer in cases of nondysplastic BE is lower than that for LGD or HGD, with rates in the literature ranging from 0.05% to 0.5%.^1,2,

Fleischer et al (2008, 2010) reported on the 5-year follow-up of a single-arm study of patients with nondysplastic BE treated with RFA.^30,31, The original study included 70 patients who underwent circumferential RFA and CR-IM, defined as complete eradication of nondysplastic BE.^30, CR-IM was seen in 70% of patients at 1-year follow-up; patients with persistent BE underwent focal RFA. At the 2.5-year follow-up, CR-IM was found in 60 (98%) of 61 patients.^30, At 5-year follow-up, 4-quadrant biopsies were obtained from every 1 cm of the original extent of BE, and the authors reported the proportion of patients demonstrating CR-IM.^31, If nondysplastic BE was identified at the 5-year follow-up, focal RFA was performed 1 month later, and biopsies were repeated 2 months afterward to assess histologic response. Primary outcomes were the proportion of patients demonstrating CR-IM at a 5-year biopsy or after a single session of focal RFA. For the 5-year follow-up, there were 60 eligible patients, 50 (83%) of whom participated. Forty-six (92%) of 50 patients showed CR-IM at the 5-year biopsy visit. The 4 patients found to have BE at 5 years underwent a single session of RFA 1 month after biopsy; all 4 patients had CR-IM at subsequent rebiopsy 2 months after RFA. No strictures were noted. The authors concluded that this first report of 5-year CR-IM outcomes supported the safety, efficacy, and reduction in neoplastic progression in treating nondysplastic BE with RFA.

Section Summary: RFA for BE Without Dysplasia

Nondysplastic BE has a relatively low rate of progression to cancer. Although available research has indicated that nondysplastic metaplasia can be eradicated by RFA, the risk-benefit ratio and the net effect on health outcomes is uncertain.

For individuals who have BE without dysplasia who receive endoscopic RFA, the evidence includes single-arm studies reporting outcomes after RFA. The relevant outcomes are OS, change in disease status, morbid events, and treatment-related morbidity and mortality. The available studies have suggested that nondysplastic metaplasia can be eradicated by RFA. However, the risk-benefit ratio and the net effect of RFA on health outcomes are unknown. The evidence is insufficient to determine the effects of technology on net health outcomes.

Population Reference No. 4

Cryoablation of Barrett Esophagus

Clinical Context and Therapy Purpose

The purpose of endoscopic cryoablation in patients who have BE is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICOs were used to select literature to inform this review.

Patients

The relevant population of interest are patients with BE with or without dysplasia.

Interventions

The therapy being considered is endoscopic cryoablation. Endoscopic cryoablation is administered in an outpatient care setting by gastroenterologists.

Comparators

The following therapies and practices are currently being used to treat BE: esophagectomy, endoscopic mucosal resection, and surveillance. Esophagectomy is an inpatient procedure performed in a tertiary care facility; endoscopic mucosal resection is an outpatient procedure performed in a tertiary care facility or specialized clinic.

Outcomes

The general outcomes of interest are symptoms (eg, pain), functional outcomes (including swallowing), and cancer-specific survival.

Beneficial outcomes include reductions in mortality.

Harmful outcomes include damage to the esophagus resulting in difficulty swallowing.

Morbidity would be assessed within 30 days after the procedure. OS and disease-specific survival would be measured at three to five years.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Several meta-analyses have evaluated the efficacy of cryotherapy in patients with BE (Tables 1, 2, and 3). Papaefthymiou et al (2024) conducted a meta-analysis comparing cryoablation with RFA in patients with BE.^32, A total of 23 studies were identified and 4 were comparative. No significant differences in complete eradication of dysplasia or complete eradication of intestinal metaplasia were found between groups.

Tariq et al (2021) performed a meta-analysis of 14 retrospective and prospective observational studies (N=405) of patients with BE who were treated with cryotherapy.^33, The primary outcome of proportions of patients achieving complete eradication of dysplasia and complete eradication of intestinal metaplasia were 84.8% (95% CI, 72.2% to 94.4%) and 64.2% (95% CI, 52.9% to 74.8%), respectively. Both outcomes had a high degree of heterogeneity (I² of 88.3% and 77.9%, respectively). Subgroup analyses of only high-quality studies revealed rates of 91.3% (95% CI, 83.0% to 97.4%; I²=69.5%) and 71.6% (95% CI, 59.0% to 82.9% ;I²=80.9%), respectively.

In their meta-analysis, Westerveld et al (2020) evaluated 7 prospective and retrospective cohort studies that reported outcomes of balloon cryoablation across 272 patients with BE; 3 of the included studies were previously reported in abstract form only.^34, The pooled proportion for complete eradication of intestinal metaplasia was 85.8% (95% CI, 77.8% to 92.2%). Among 262 patients with BE with dysplasia, 238 reported complete eradication of dysplasia after cryoablation (pooled proportion, 93.8%; 95% CI, 85.5% to 98.7%). Both outcomes had a high degree of heterogeneity (I² of 55% and 74.2%, respectively). However, when 2 low quality studies were excluded from the analysis, results were consistent with the primary analysis. Adverse events were reported in 12.5% of patients, representing 34 adverse events. Half of the adverse events (n=16) were post-ablation stricture formation (5.8%).

Hamade et al (2019) evaluated the use of cryotherapy for BE in patients who were previously treatment-naive.^35, Six uncontrolled trials were included in the systematic review, which included 232 patients overall. Complete eradication of intestinal metaplasia was achieved in 69.35% of cases (95% CI, 52.1% to 86.5%; I²=89.3%). Complete eradication of dysplasia was achieved in 90.6% of cases (95% CI, 83.7% to 97.4%; I²=75.7%). Progression to cancer occurred in 4% of cases (9/225). The pooled recurrence rate of intestinal metaplasia was 19.1 per 100 patient-years. The post-procedure stricture formation rate was 4.9%, and 3.9% of patients reported postprocedural pain.

Table 1. Comparison of Studies Included in Systematic Reviews and Meta-Analyses

Table 2. Systematic Review and Meta-Analysis Characteristics

  BE: Barrett's esophagus; NR: not reported. 

Table 3. Systematic Review and Meta-Analysis Results

  CI: confidence interval; OR, odds ratio. 

Prospective and Retrospective Studies

Several small prospective and retrospective uncontrolled studies of cryoablation have been published (Tables 4 and 5). These studies are heterogenous in the proportion of patients with prior BE treatment, cryoablation techniques used, and follow-up duration.

Table 4. Summary of Key Nonrandomized Studies

  BE: Barrett's esophagus; HGD: high-grade dysplasia; LGD: low-grade dysplasia; RFA: radiofrequency ablation.

Table 5. Summary of Key Nonrandomized Study Results

  HGD: high-grade dysplasia; NR: not reported; RFA: radiofrequency ablation.

Section Summary: Cryoablation of Barrett Esophagus

No controlled trials have evaluated cryoablation for the treatment of BE. The evidence from uncontrolled studies has reported high rates of success in eradicating dysplasia, with low rates of complications. These data are not sufficient to determine the comparative efficacy of cryoablation and RFA.

For individuals who have BE with or without dysplasia who receive endoscopic cryoablation, the evidence includes noncomparative studies reporting outcomes after cryoablation. The relevant outcomes include OS, change in disease status, morbid events, and treatment-related morbidity and mortality. These studies have generally demonstrated high rates of eradication of dysplasia. However, the available evidence does not compare cryoablation with surgical care or RFA. The evidence is insufficient to determine the effects of technology on net health outcomes.

Supplemental Information

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2012 Input

In response to requests, input was received from reviewers at 6 academic medical centers and from 1 subspecialty medical society while this policy was under review in 2012. Input related to the treatment of low-grade dysplasia (LGD) was mixed, with two reviewers stating that radiofrequency ablation (RFA) for LGD should be investigational, three indicating that it should be medically necessary, and two indicating that it was a split decision. There was a general consensus among reviewers that there are subsets of patients with LGD who have a higher risk and should, therefore, be treated. Reviewers mentioned that factors useful in defining higher risk populations for whom treatment is warranted are the confirmation of LGD diagnosis by multiple pathologists and/or the application of clinical high-risk factors such as lesion length.

2009 Input

In response to requests, input was received from 3 academic medical centers and 1 subspecialty medical society (with 12 reviewers) while this policy was under review in 2009. All reviewers agreed that RFA (cryoablation was not included in the request) should be considered medically necessary for the treatment of Barrett esophagus (BE) with high-grade dysplasia. Reviewers were split for the use of RFA for LGD, with nine considered it medically necessary and four considering it investigational.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American College of Gastroenterology

In 2022, the American College of Gastroenterology (ACG) updated guidelines on the diagnosis and management of BE, which made statements about ablation techniques^41, The ACG recommends ablation of remaining BE tissue when endoscopic eradication therapy is chosen for patients with LGD, HGD, or intramucosal carcinoma. Both RFA and cryoablation are discussed in the ACG guideline without a specific recommendation; however, the guideline notes the lack of randomized controlled trials (RCTs) for cryoablation methods and the more established evidence for RFA. The ACG does recommend cryotherapy as an alternative in patients unresponsive to RFA.

American Gastroenterological Association

In 2024 , the American Gastroenterological Association (AGA) published a clinical guideline on the role of endoscopic therapy in patients with BE and related neoplasia.^42,

The AGA guideline made 5 recommendation for endoscopic eradication of BE:

• "In individuals with BE with HGD, the AGA recommends EET over surveillance. (Strong recommendation, moderate certainty of evidence)"

• "In individuals with BE with LGD, the AGA suggests for EET over surveillance. Patients who place a higher value on the well-defined harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality would reasonably select surveillance endoscopy. (Conditional recommendation, low certainty of evidence)"

• "In individuals with NDBE [nondysplastic BD], the AGA suggests against the routine use of EET. (Conditional recommendation, very low certainty of evidence)"

• "In patients undergoing EET, the AGA suggests resection of visible lesions followed by ablation of the remaining BE segment over resection of the entire BE segment. (Conditional recommendation, very low certainty of evidence)"

  • "RFA is the preferred ablative modality."

• "In individuals with BE with visible neoplastic lesions that are undergoing endoscopic resection, the AGA suggests the use of either EMR [endoscopic mucosal resection] or ESD [endoscopic submucosal resection] based on lesion characteristics. (Conditional recommendation, very low certainty of evidence)"

American Society for Gastrointestinal Endoscopy

In 2018, the American Society for Gastrointestinal Endoscopy (ASGE) issued guidelines on the role of endoscopy in BE-associated dysplasia and intramucosal cancer.^43, These guidelines made the following recommendations on endoscopic eradication therapy, consisting of endoscopic mucosal resection of visible lesions and ablative techniques that include RFA and cryotherapy (see Table 6 ).

Table 6. ASGE Guidelines on Use of Endoscopy for Barrett Esophagus and Intramucosal Cancer

  BE: Barrett esophagus; CE-IM: complete eradication of intestinal metaplasia; EET: endoscopic eradication therapy; GI: gastrointestinal; HGD: high-grade dysplasia; IMC: intramucosal cancer; LGD: low-grade dysplasia; QOE: quality of evidence; SOR: strength of recommendation. aQuality assessed using GRADE system.

National Comprehensive Cancer Network

National Comprehensive Cancer Network Guidelines (v.4.2024 ) on esophageal and esophagogastric junction cancers make recommendations about BE and early-stage esophageal adenocarcinomas.^44, For primary treatment; “The goal of endoscopic therapy [by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and/or ablation] is the complete removal or eradication of early-stage disease [pTis, pT1a, and selected superficial pT1b without LVI] and pre-neoplastic tissue (Barrett esophagus)."

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

Some currently ongoing and unpublished trials that might influence this review are listed in Table 7.

Table 7. Summary of Key Trials

  NCT: national clinical trial. aDenotes industry sponsored or co-sponsored trial. 

References

1. Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst. Jul 06 2011; 103(13): 1049-57. PMID 21680910
2. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med. Oct 13 2011; 365(15): 1375-83. PMID 21995385
3. Downs-Kelly E, Mendelin JE, Bennett AE, et al. Poor interobserver agreement in the distinction of high-grade dysplasia and adenocarcinoma in pretreatment Barrett's esophagus biopsies. Am J Gastroenterol. Sep 2008; 103(9): 2333-40; quiz 2341. PMID 18671819
4. Yerian L. Histology of metaplasia and dysplasia in Barrett's esophagus. Surg Oncol Clin N Am. Jul 2009; 18(3): 411-22. PMID 19500733
5. Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. Mar 2008; 103(3): 788-97. PMID 18341497
6. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Radiofrequency ablation of nondysplastic or low-grade dysplastic Barretts esophagus. TEC Assessments. 2010;Volume 25:Tab 5.
7. Kerkhof M, van Dekken H, Steyerberg EW, et al. Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology. Jun 2007; 50(7): 920-7. PMID 17543082
8. Curvers WL, ten Kate FJ, Krishnadath KK, et al. Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated. Am J Gastroenterol. Jul 2010; 105(7): 1523-30. PMID 20461069
9. Phoa KN, van Vilsteren FG, Weusten BL, et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. Mar 26 2014; 311(12): 1209-17. PMID 24668102
10. Duits LC, Phoa KN, Curvers WL, et al. Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut. May 2015; 64(5): 700-6. PMID 25034523
11. Ell C, May A, Pech O, et al. Curative endoscopic resection of early esophageal adenocarcinomas (Barrett's cancer). Gastrointest Endosc. Jan 2007; 65(1): 3-10. PMID 17185072
12. Pech O, Ell C. Endoscopic therapy of Barrett's esophagus. Curr Opin Gastroenterol. Sep 2009; 25(5): 405-11. PMID 19474724
13. Overholt BF, Lightdale CJ, Wang KK, et al. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial. Gastrointest Endosc. Oct 2005; 62(4): 488-98. PMID 16185958
14. Ganz RA, Overholt BF, Sharma VK, et al. Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. Multicenter Registry. Gastrointest Endosc. Jul 2008; 68(1): 35-40. PMID 18355819
15. Food and Drug Administration. 510(k) Summary: BARRX Channel RFA Endoscopic Catheter. No. K130623. 2013; https://www.accessdata.fda.gov/cdrh_docs/pdf13/K130623.pdf. Accessed September 21, 2024.
16. Food and Drug Administration. 510(k) Safety Summary: CryoSpray Ablation System. No. K072651. 2007; https://www.accessdata.fda.gov/cdrh_docs/pdf7/K072651.pdf. Accessed September 20, 2024.
17. Food and Drug Administration. 510(k) Summary: C2 Cryoballoon Ablation System. No. K163684. 2018; https://www.accessdata.fda.gov/cdrh_docs/pdf16/K163684.pdf. Accessed September 23, 2024.
18. PR Newswire. Pentax Medical Introduces Next-Generation C2 Cryoballoon Ablation System for Treatment of Barrett's Esophagus. 2018. https://www.prnewswire.com/news-releases/pentax-medical-introduces-next-generation-c2-cryoballoon-ablation-system-for-treatment-of-barretts-esophagus-300658152.html. Accessed September 23, 2024.
19. U.S. Food and Drug Administration. 510(k) Premarket Notification to Check-Med Systems, Inc. 2002; https://www.accessdata.fda.gov/cdrh_docs/pdf2/k021387.pdf. Accessed September 23, 2024.
20. Eloubeidi MA, Wallace MB, Hoffman BJ, et al. Predictors of survival for esophageal cancer patients with and without celiac axis lymphadenopathy: impact of staging endosonography. Ann Thorac Surg. Jul 2001; 72(1): 212-9; discussion 219-20. PMID 11465182
21. National Cancer Institute. Esophageal Cancer. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/esophageal. Accessed September 23, 2024.
22. Chadwick G, Groene O, Markar SR, et al. Systematic review comparing radiofrequency ablation and complete endoscopic resection in treating dysplastic Barrett's esophagus: a critical assessment of histologic outcomes and adverse events. Gastrointest Endosc. May 2014; 79(5): 718-731.e3. PMID 24462170
23. van Vilsteren FG, Pouw RE, Seewald S, et al. Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. Gut. Jun 2011; 60(6): 765-73. PMID 21209124
24. Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. May 28 2009; 360(22): 2277-88. PMID 19474425
25. Shaheen NJ, Overholt BF, Sampliner RE, et al. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. Aug 2011; 141(2): 460-8. PMID 21679712
26. Phoa KN, Pouw RE, Bisschops R, et al. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut. Apr 2016; 65(4): 555-62. PMID 25731874
27. Wang Y, Ma B, Yang S, et al. Efficacy and Safety of Radiofrequency Ablation vs. Endoscopic Surveillance for Barrett's Esophagus With Low-Grade Dysplasia: Meta-Analysis of Randomized Controlled Trials. Front Oncol. 2022; 12: 801940. PMID 35296005
28. Klair JS, Zafar Y, Nagra N, et al. Outcomes of Radiofrequency Ablation versus Endoscopic Surveillance for Barrett's Esophagus with Low-Grade Dysplasia: A Systematic Review and Meta-Analysis. Dig Dis. 2021; 39(6): 561-568. PMID 33503615
29. Pandey G, Mulla M, Lewis WG, et al. Systematic review and meta-analysis of the effectiveness of radiofrequency ablation in low grade dysplastic Barrett's esophagus. Endoscopy. Oct 2018; 50(10): 953-960. PMID 29689573
30. Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up. Gastrointest Endosc. Nov 2008; 68(5): 867-76. PMID 18561930
31. Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy. Oct 2010; 42(10): 781-9. PMID 20857372
32. Papaefthymiou A, Norton B, Telese A, et al. Efficacy and Safety of Cryoablation in Barrett's Esophagus and Comparison with Radiofrequency Ablation: A Meta-Analysis. Cancers (Basel). Aug 23 2024; 16(17). PMID 39272792
33. Tariq R, Enslin S, Hayat M, et al. Efficacy of Cryotherapy as a Primary Endoscopic Ablation Modality for Dysplastic Barrett's Esophagus and Early Esophageal Neoplasia: A Systematic Review and Meta-Analysis. Cancer Control. 2020; 27(1): 1073274820976668. PMID 33297725
34. Westerveld DR, Nguyen K, Banerjee D, et al. Safety and effectiveness of balloon cryoablation for treatment of Barrett's associated neoplasia: systematic review and meta-analysis. Endosc Int Open. Feb 2020; 8(2): E172-E178. PMID 32010750
35. Hamade N, Desai M, Thoguluva Chandrasekar V, et al. Efficacy of cryotherapy as first line therapy in patients with Barrett's neoplasia: a systematic review and pooled analysis. Dis Esophagus. Dec 30 2019; 32(11). PMID 31076753
36. Agarwal S, Alshelleh M, Scott J, et al. Comparative outcomes of radiofrequency ablation and cryoballoon ablation in dysplastic Barrett's esophagus: a propensity score-matched cohort study. Gastrointest Endosc. Mar 2022; 95(3): 422-431.e2. PMID 34624303
37. Fasullo M, Shah T, Patel M, et al. Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus. Dig Dis Sci. Jun 2022; 67(6): 2320-2326. PMID 33954846
38. Sengupta N, Ketwaroo GA, Bak DM, et al. Salvage cryotherapy after failed radiofrequency ablation for Barrett's esophagus-related dysplasia is safe and effective. Gastrointest Endosc. Sep 2015; 82(3): 443-8. PMID 25887715
39. Shaheen NJ, Greenwald BD, Peery AF, et al. Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia. Gastrointest Endosc. Apr 2010; 71(4): 680-5. PMID 20363409
40. 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. Oct 2009; 70(4): 635-44. PMID 19559428
41. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. Apr 01 2022; 117(4): 559-587. PMID 35354777
42. Rubenstein JH, Sawas T, Wani S, et al. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia. Gastroenterology. Jun 2024; 166(6): 1020-1055. PMID 38763697
43. Wani S, Qumseya B, Sultan S, et al. Endoscopic eradication therapy for patients with Barrett's esophagus-associated dysplasia and intramucosal cancer. Gastrointest Endosc. Apr 2018; 87(4): 907-931.e9. PMID 29397943
44. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. Version 4.2024. https://www.nccn.org/professionals/physician_gls/PDF/esophageal.pdf. Accessed September 23, 2024.

CODES

Applicable Modifiers

As per correct coding guidelines

Policy History