Prior authorization request form Form

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 PAYMENT POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM

EFFECTIVE DATE: 02|19|2013 POLICY LAST UPDATED: 07|05|2023

iOVERVIEW Chromoendoscopy refers to the use of dyes or stains during endoscopy to enhance tissue differentiation or characterization. When used with colonoscopy, the intent is to increase the sensitivity of the procedure by facilitating the identification of mucosal abnormalities. There are two types of chromoendoscopy: one involves actual spraying of dyes or stains through the working channel of an endoscope; the other, known as virtual chromoendoscopy, uses a computer algorithm to simulate different colors of light that result from dye or stain spraying.

MEDICAL CRITERIA Not applicable

PRIOR AUTHORIZATION
Not applicable

POLICY STATEMENT Medicare Advantage Plans and Commercial Products Chromoendoscopy and virtual chromoendoscopy as an adjunct to diagnostic or surveillance colonoscopy is considered incidental to the colonoscopy and therefore is not separately reimbursed.

COVERAGE Benefits may vary between groups/contracts. Please refer to the appropriate Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for applicable surgery benefit/coverage.

BACKGROUND Several adjunct endoscopic techniques, including chromoendoscopy, could enhance the sensitivity of colonoscopy. Chromoendoscopy, also known as chromoscopy and chromocolonoscopy, refers to the application of topical stains or dyes during endoscopy to enhance tissue differentiation or characterization and facilitate identification of mucosal abnormalities. Chromoendoscopy may be particularly useful for detecting flat or depressed lesions. A standard colonoscopy uses white-light to view the colon. In chromoendoscopy, stains are applied, resulting in color highlighting of areas of surface morphology of epithelial tissue. The dyes or stains are applied via a spray catheter that is inserted down the working channel of the endoscope. Chromoendoscopy can be used in the whole colon (pancolonic chromoendoscopy) on an untargeted basis or can be directed to a specific lesion or lesions (targeted chromoendoscopy). Chromoendoscopy differs from endoscopic tattooing in that the former uses transient stains, whereas tattooing involves the use of a long-lasting pigment for future localization of lesions.

Stains and dyes used in chromoendoscopy can be placed in the following categories: • Absorptive stains are preferentially absorbed by certain types of epithelial cells. • Contrast stains seep through mucosal crevices and highlight surface topography. • Reactive stains undergo chemical reactions when in contact with specific cellular constituents, which results in a color change. Payment Policy | Chromoendoscopy as an Adjunct to Colonoscopy

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 PAYMENT POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

Indigo carmine, a contrast stain, is the most commonly used stain with colonoscopy to enhance the detection of colorectal neoplasms. Several absorptive stains are also used with colonoscopy. Methylene blue, which stains the normal absorptive epithelium of the small intestine and colon, has been used to detect colonic neoplasia and to aid in the detection of intraepithelial neoplasia in patients with chronic ulcerative colitis. In addition, crystal violet (also known as gentian violet) stains cell nuclei and has been applied in the colon to enhance visualization of pit patterns (ie, superficial mucosal detail). Reactive stains are primarily used to identify gastric abnormalities and are not used with colonoscopy. Potential applications of chromoendoscopy as an adjunct to standard colonoscopy include: • Diagnosis of colorectal neoplasia in symptomatic patients at increased risk of Colorectal cancer CRC due to a family history of CRC, a personal history of adenomas, etc. • Identification of mucosal abnormalities for targeted biopsy as an alternative to multiple random biopsies in patients with inflammatory bowel disease. • Screening the general population for CRC. The equipment used in regular chromoendoscopy is widely available. Several review articles and technology assessments have indicated that, although the techniques are simple, the procedure (eg, the concentration of dye and amount of dye sprayed) is variable, and thus classification of mucosal staining patterns for identifying specific conditions is not standardized. Virtual chromoendoscopy (also called electronic chromoendoscopy) involves imaging enhancements with endoscopy systems that could be an alternative to dye spraying. One system is the Fujinon Intelligent Color Enhancement feature (Fujinon Inc.). This technology uses postprocessing computer algorithms to modify the light reflected from the mucosa from conventional white-light to various other wavelengths. Regulatory Status In 2014, the Fujifilm EPX-4440HD Digital Video Processor with Fujinon Intelligent Color Enhancement (FICE®) and Light Source was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA documents stated that FICE® could be used to supplement white-light endoscopy but is not intended to replace histopathologic sampling as a means of diagnosis. In 2013, the i-SCAN™ (Pentax), used for virtual chromoendoscopy, was cleared for marketing by the FDA through the 510(k) process. This digital image enhancement technology is part of the Pentax EPK-i5010 Video Processor. The i-SCAN™ has several modes that digitally enhance images in real-time during endoscopy. The FDA documents stated that i-SCAN™ is intended as an adjunct following white-light endoscopy but not intended to replace histopathologic analysis. No dye or stain product has been specifically approved by the FDA for use in chromoendoscopy. Chromoendoscopy For individuals who have an average risk of CRC who receive chromoendoscopy, the evidence includes an RCT evaluating this population. The relevant outcomes are overall survival (OS), disease-specific survival (DSS), test validity, and change in disease status. The single RCT did not find that high-definition chromoendoscopy identified more clinically meaningful lesions than high-definition white-light colonoscopy. The evidence is insufficient to determine the effects of technology on net health outcomes. For individuals who have an increased risk of CRC who receive chromoendoscopy, the evidence includes multiple RCTs, back-to-back colonoscopy studies, and systematic reviews. The relevant outcomes are OS, DSS, test validity, and change in disease status. A Cochrane systematic review of trials comparing chromoendoscopy with standard colonoscopy in high-risk patients (but excluding those with IBD) found significantly higher rates of adenoma detection and rates of three or more adenomas with chromoendoscopy

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 PAYMENT POLICY | 3 (401) 274-4848 WWW.BCBSRI.COM

than with standard colonoscopy. The evidence for detecting larger polyps, defined as greater than 5 mm or greater than 10 mm, is less robust. While one study reported a significantly higher detection rate for polyps greater than 5 mm, no studies reported increased detection of polyps greater than 10 mm. The evidence is insufficient to determine the effects of technology on net health outcomes. For individuals who have IBD who receive chromoendoscopy, the evidence includes observational studies and meta-analyses of observational data. The relevant outcomes are OS, DSS, test validity, and change in disease status. One meta-analysis found a statistically significant higher yield of chromoendoscopy over white- light colonoscopy for detecting dysplasia. This evidence established that chromoendoscopy improves polyp detection rates; however, it is unclear whether the additional polyps detected are clinically important and, therefore, whether improved polyp detection rates will translate into improved health outcomes. Moreover, there are concerns about comparison groups used in some of these trials. It is uncertain whether the control groups received optimal colonoscopy; therefore, the improved detection rates by chromoendoscopy might have been a function of suboptimal standard colonoscopy. The evidence is insufficient to determine the effects of technology on net health outcomes. Virtual Chromoendoscopy For individuals who have an average risk of CRC who receive virtual chromoendoscopy, the evidence includes several RCTs and a meta-analysis. The relevant outcomes are OS, DSS, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of the technology on net health outcomes. For individuals who have an increased risk of CRC who receive virtual chromoendoscopy, the evidence includes several RCTs and a meta-analysis. The relevant outcomes are OS, DSS, test validity, and change in disease status. The available RCTs have not found that virtual chromoendoscopy improves the detection of clinically important polyps compared with standard white-light colonoscopy. Moreover, there is a lack of studies assessing the impact of virtual chromoendoscopy on CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of technology on net health outcomes. For individuals who have IBD who receive virtual chromoendoscopy, the evidence includes an RCT and nonrandomized comparative study. The relevant outcomes are OS, DSS, test validity, and change in disease status. The RCT found a significantly greater likelihood that virtual chromoendoscopy would correctly identify the extent of disease inflammation than standard colonoscopy but no significant difference in the likelihood of identifying disease activity. A retrospective cohort study found that targeted biopsy resulted in a higher rate of neoplasia detection regardless of the endoscopy method used. There is a lack of studies assessing the impact of virtual chromoendoscopy CRC incidence and mortality rates compared with standard colonoscopy. The evidence is insufficient to determine the effects of technology on net health outcomes. CODING BlueCHiP for Medicare and Commercial Products There is no specific CPT coding for chromoendoscopy.

If the chromoendoscopy is reported, use the unlisted CPT code 44799, unlisted procedure, intestine.

RELATED POLICIES None

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 PAYMENT POLICY | 4 (401) 274-4848 WWW.BCBSRI.COM

PUBLISHED Provider Update, September 2023 Provider Update, March 2020 Provider Update, March 2018 Provider Update, March 2017 Provider Update, March 2016 Provider Update, June 2015 Provider Update, Aug 2014 Provider Update, May 2013

REFERENCES

1. Van Rijn J. C, Reitsma JB, Stoker J, et al. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol. 2006; 101(2):343-350.
2. Brown SR, Baraza W. Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database Syst Rev 2010; (10):CD006439.
3. Pohl J, Schneider A, Vogell H et al. Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomized two-centre trial. Gut 2011; 60(4):485-90.
4. LeRhun M, Coron E, Parlier D, et al. High resolution colonoscopy with chromoscopy versus standard colonoscopy for the detection of colonic neoplasia: a randomized study. Clin Gastroenterol Hepatol.2006;4(3):349-354
5. Subramanian V, Mannath J, Ragunath K et al. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33(3):304-12.
6. Freire P, Figueiredo P, Cardoso R, et al. Surveillance in ulcerative colitis: is chromoendoscopy-guided endomicroscopy always better than conventional colonoscopy? A randomized trial. Inflamm Bowel Dis. Nov 2014; 20(11):2038-2045. PMID 25185683
7. Freire P, Figueiredo P, Cardoso R, et al. Surveillance in ulcerative colitis: is chromoendoscopy-guided endomicroscopy always better than conventional colonoscopy? A randomized trial. Inflamm Bowel Dis. Nov 2014; 20(11):2038-2045. PMID 25185683
8. Omata F, Ohde S, Deshpande GA, et al. Image-enhanced, chromo, and cap-assisted colonoscopy for improving adenoma/neoplasia detection rate: a systematic review and meta-analysis. Scand J Gastroenterol. Feb 2014; 49(2):222-237. PMID 24328858
9. Mooiweer E, van der Meulen-de Jong AE, Ponsioen CY, et al. Chromoendoscopy for surveillance in inflammatory bowel disease does not increase neoplasia detection compared with conventional colonoscopy with random biopsies: results from a large retrospective study. Am J Gastroenterol. Jul 2015; 110(7):1014-
10. PMID 25823770
11. Laine L, Kaltenbach T, Barkun A, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. Mar 2015; 148(3):639-651 e628. PMID 25702852
12. Marion JF, Sands BE. The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution. Gastroenterology. Mar 2015;148(3):462-467. PMID 25702851 12. Marion JF, Waye JD, Israel Y, et al. Chromoendoscopy is more effective than standard colonoscopy in detecting dysplasia during long-term surveillance of patients with colitis. Clin Gastroenterol Hepatol. May 2016; 14(5):713-719. PMID 26656297
13. Gasia MF, Ghosh S, Panaccione R, et al. Targeted biopsies identify larger proportions of patients with colonic neoplasia undergoing high-definition colonoscopy, dye chromoendoscopy, or electronic virtual chromoendoscopy. Clin Gastroenterol Hepatol. May 2016; 14(5):704-712 e704. PMID 26804384
14. U.S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. Jun 21 2016; 315(23):2564-
15. PMID 27304597

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 PAYMENT POLICY | 5 (401) 274-4848 WWW.BCBSRI.COM

15. Abu Dayyeh BK, Thosani N, Konda V, et al. ASGE Technology Committee systematic review and meta- analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2015; 81(3):502.e501-502.e516. PMID 25597420

    This medical policy is made available to you for informational purposes only. It is not a guarantee of payment or a substitute for your medical judgment in the treatment of your patients. Benefits and eligibility are determined by the member's subscriber agreement or member certificate and/or the employer agreement, and those documents will supersede the provisions of this medical policy. For information on member-specific benefits, call the provider call center. If you provide services to a member which are determined to not be medically necessary (or in some cases medically necessary services which are non-covered benefits), you may not charge the member for the services unless you have informed the member and they have agreed in writing in advance to continue with the treatment at their own expense. Please refer to your participation agreement(s) for the applicable provisions. This policy is current at the time of publication; however, medical practices, technology, and knowledge are constantly changing. BCBSRI reserves the right to review and revise this policy for any reason and at any time, with or without notice. Blue Cross & Blue Shield of Rhode Island is an independent licensee of the Blue Cross and Blue Shield Association. CLICK THE ENVELOPE ICON BELOW TO SUBMIT COMMENTS