Archived Policies - Medicine
In Vivo Analysis of Colorectal Polyps
In vivo analysis of colorectal polyps is considered experimental, investigational and/or unproven.
During a colonoscopy or sigmoidoscopy as a screening test for colorectal cancer, the physician must often decide which polyp should be removed for histologic diagnosis. While hyperplastic polyps are considered benign without malignant potential, adenomatous polyps are thought to represent one of the earliest stages in the progression to a malignancy. Identification of these premalignant lesions is considered one of the cornerstones of colorectal cancer prevention. The physician must thus balance the time and potential morbidity of removing all polyps, many of which will be benign, versus removal of those polyps most likely to be adenomatous. Techniques have been developed as adjuncts to colonoscopy that are intended to distinguish between normal and precancerous tissue.
The first system developed was based on the observation that benign and malignant tissues emit different patterns and wavelengths of fluorescence after exposure to a laser light. One such device was approved by the U.S. Food and Drug Administration (FDA) in 2000, the Optical Biopsy System (SpectraScience, Minneapolis MN). This system consists of an optical fiber emitting a laser that is directed against three different regions of the same polyp. The subsequent fluorescent signal is collected, measured, and analyzed by a proprietary system software, and classifies a polyp as "suspicious" (i.e., adenomatous) or "not suspicious" (i.e., hyperplastic).
Narrow band imaging (NBI) is another technique that allows visualization of the mucosal surface and capillary vessels and thus may assist in the differentiation of abnormal from normal mucosa during colonoscopy. Two NBI systems are available. The NBI color chip system is used in the United States; in this system a single filter with a 2-band pass characteristic is used to generate central wavelengths at 415 nm (blue) and 540 nm (green and red). The NBI red-green-blue sequential illumination system uses narrow spectra of red, green, and blue light and a video endoscopic system with a frame sequential lighting method. The light source unit consists of a xenon lamp and a rotation disk with 3 optical filters. The rotation disk and monochrome charge-coupled device are synchronized and sequentially generate image in 3 optical filter bands. By use of all 3 band images, a single color endoscopic image is synthesized by the video processor. NBI has limited penetration into the mucosal surface and has enhanced visualization of capillary vessels and their fine structure on the surface layer of colonic tissue.
The FDA-labeled indication for the Optical Biopsy System reads as follows: "The SpectraScience Optical Biopsy System is indicated for use as an adjunct to lower gastrointestinal endoscopy. The device is intended for the evaluation of polyps less than 1 cm in diameter that the physician has not already elected to remove. The device is only to be used in deciding whether such polyps should be removed (which includes submission for histological examination)."
NBI received FDA clearance through the 510(k) process in 2005. This clearance (K051645) added NBI with the EVIS EXERA 160A System (Olympus Medical Systems Corp) to existing endoscopic equipment. FDA indications are for endoscopic diagnosis, treatment, and video observation.
Optical Biopsy System
The U.S. Food and Drug Administration (FDA) approval for the Optical Biopsy System was based on a prospective, nonrandomized Phase II study involving 101 subjects from 5 sites. The data from this trial have not been published in a peer-reviewed journal but are available as an FDA summary of safety and effectiveness. (1) Patients who participated in the study had undergone a prior lower gastrointestinal endoscopic procedure with at least 1 polyp identified, and were referred for an additional colonoscopy exam, in which fiberoptic analysis of the polyps was performed. At the time of the colonoscopy, the physicians documented whether or not the polyp was considered hyperplastic or adenomatous, and whether or not they would remove the polyp. The fiberoptic probe was then applied to 3 different portions of the polyp and a segment of normal adjacent mucosa. The physician did not know the results of the analysis and thus the test did not affect patient treatment. The effectiveness of the analysis was then calculated as its ability to correctly identify adenomatous polyps (i.e., sensitivity) and to correctly identify hyperplastic polyps (i.e., the specificity), either alone or in conjunction with physician assessment. The sensitivity and specificity of the physician assessment alone was 82.7% and 50%, respectively, compared to a combined sensitivity and specificity of 96.3% and 33%, respectively. In other words, fiberoptic analysis identified additional adenomatous polyps that the physician had classified as hyperplastic and presumably would not have removed based on visual assessment alone. This increase in sensitivity comes at the price of a decrease in specificity, as more hyperplastic polyps will undergo biopsy. However, according to the FDA, the risk of taking biopsies of additional hyperplastic polyps is minimal.
The clinical significance of these results and their effect on patient management is difficult to interpret from the data presented. It is not clear how the physician decided to select additional polyps for fiberoptic analysis (it is not entirely clear whether all polyps were analyzed and then underwent biopsy), or whether the same results could be obtained by simply randomly taking a biopsy of a subset of polyps that were considered hyperplastic on visual assessment. While adenomatous polyps are considered premalignant lesions, the evolution to cancer is a slow process requiring 7 to 8 years, and thus the immediate removal of all adenomatous polyps is not required. In addition, the finding of an adenomatous polyp serves as a marker that the patient should undergo more frequent endoscopic exams. It is well known that the current practice of visual inspection of polyps will certainly miss some adenomatous polyps, but this lack of sensitivity is considered acceptable if at least 1 adenomatous polyp is identified and the patient undergoes more frequent screening.
Few data have been published on the SpectraScience Optical Biopsy System since 2002. A feasibility study of fiberoptic analysis of normal, adenomatous, and cancerous tissue in 11 patients was published in 2003. (2) No additional literature on the Optical Biopsy System was found, but a report in 2006 detailed the results of spectral scattering to different colonic lesions in a small series of 45 patients. (3)
Narrow Band Imaging (NBI)
Several studies from both outside (4-13) and inside (14-19) the United States have evaluated the NBI system. These studies are a mixture of those evaluating its overall detection rates for colonic polyps (4, 7-8, 10, 14, 17) and those specifically examining its ability to differentiate between neoplastic and non-neoplastic lesions. (9-11, 15, 16, 18, 19) Data from 4 randomized trials of NBI versus white-light colonoscopy failed to show any advantage in total detection rate for NBI. (7, 8, 14, 17) Published randomized trials differed from the conventional approach to the assessment of diagnostic tests. In these trials patients were randomized to one test or the other (i.e., they received only one test). In general, when comparing diagnostic tests we would have each patient receive both tests and compare the test results.
Adler and colleagues published 2 trials. The first trial enrolled 401 participants where the majority of the patients (89%) were enrolled for a diagnostic colonoscopy and evaluated by expert endoscopists (>500 per provider). (7) The second trial enrolled 1,256 participants evaluated with a screening colonoscopy in a private practice setting by 6 endoscopists with substantial lifetime experience (>10,000 total colonoscopies). (8) Both trials randomized participants to receive NBI or white-light colonoscopy; neither trial showed a benefit of NBI over white-light for overall polyp detection rate. In a similar study, with the same conclusion, Rex and colleagues enrolled 434 participants, in a population split between 60% screening colonoscopy and 40% returning for surveillance. (17) Each participant was randomized to either NBI or white-light colonoscopy. No benefit of NBI for the detection of adenomas was observed over white-light colonoscopy. Kaltenback and colleagues randomized 434 participants to receive both NBI and a white-light colonoscopy, or 2 white-light colonoscopies. Participants were screened by experienced endoscopists. With the first test, all visible polyps were removed, then the second test was performed to pick up any additional “missed” polyps; from this difference, the polyp miss rate was calculated. The major limitation with this method is that removing polyps with the first test eliminates the opportunity for the second test to “miss” any polyps that were already removed. NBI did not improve what was termed the “neoplasm miss rate” compared with white light. (14) Inoue and colleagues, in a randomized, controlled trial (RCT) of 243 patients in Japan, presented data showing that NBI did improve overall adenoma detection rates over conventional colonoscopy, as well as improving the number of small (<5 mm) adenomas detected, while the number of patients with at least one adenoma remained the same. (4) Participants in this trial had a previous positive colonoscopy or positive fecal occult blood test; approximately 80% were undergoing polyp surveillance. All testing was performed at an endoscopy center by 6 experienced endoscopists. Differences in results may be attributed to different study populations and/or differences in the version of NBI system used.
One randomized trial addressed both total detection rate and differentiation of neoplastic from non-neoplastic lesions. Pohl and colleagues conducted a randomized multicenter trial of virtual chromoendoscopy with the “Fujinon intelligent colour enhancement” system (FICE or NBI) versus standard colonoscopy with targeted indigocarmine chromoscopy. (10) This German trial included 764 patients in the final analysis and reported that FICE/NBI was not superior to control for overall adenoma detection rates; it was comparable on the differentiation of neoplastic and non-neoplastic lesions. The sensitivity of FICE/NBI was 92.7% versus 90.4% for the control. Additional data on NBI for the differentiation of neoplastic from non-neoplastic lesions comes from nonrandomized studies of various sizes where the conclusion often is that NBI may be more accurate than conventional colonoscopy for the differentiation of lesions. (9, 15, 16, 18, 19)
For example, Hirata evaluated 148 colorectal lesions and concluded that determination of pit patterns of colorectal neoplasia by NBI magnification was nearly the same as that by standard magnification with chromoendoscopy and that NBI can distinguish neoplastic and non-neoplastic lesions without chromoendoscopy. (12) Rastogi and colleagues, after evaluating 100 patients with 236 detected polyps, concluded that NBI without magnification was significantly superior to high-definition white-light colonoscopy for the real-time prediction of adenomas. (16) van den Broek reported sensitivity, specificity, and overall accuracy of NBI for differentiation of 90%, 70%, and 79%, respectively, and while the specificity and overall accuracy were superior to high-resolution endoscopy, endoscopic trimodal imaging and autofluorescence imaging, the test characteristics were disappointing for the diagnostic accuracy for polyp differentiation. (11) These studies only reported on the accuracy of the NBI system in the in vivo evaluation of colonic polyps. None of the studies evaluated the impact of this technology on outcomes including whether or not there would be an improvement in the selection of polyps for removal during colonoscopy.
In an editorial, Soetikno mentions the need for a user-friendly classification system for use of these devices. (20) The editorial also comments on the need for high-definition recording devices to allow further research. As noted, without these devices, the details of lesions cannot be seen beyond the fleeting moment during the procedure and patterns cannot be fully correlated with pathology. Current technology allows for images to be saved and reviewed at a later time, but development of a standardized system for the classification of the different patterns seen on NBI is needed. (21)
While other technologies are under investigation, including chromocolonoscopy, (5, 6) Third Eye Retroscope, (22) and autofluorescence, (23) there is no evidence that current studies of these technologies overcome the issues referenced. Randomized trial data, in which participants receive both screening tests, and histologic confirmation of disease is matched to screening test results for each polyp are required to evaluate this technology.
The impact of this technology on health outcomes is not known.
Technology Assessments, Guidelines, and Position Statements
Neither the U.S. Preventive Services Task Force nor the National Comprehensive Cancer Network (NCCN) mentions NBI in their current policy statements or screening guidelines. The American Gastroenterological Association in 2008 published a technology assessment of image-enhanced endoscopy, which mentions optical and electronic devices potentially playing a role in colon screening in the future, but currently, more data are needed. (24)
A search of peer reviewed literature through November 2013 failed to find any new data on the Optical Biopsy System, while NBI has several randomized, controlled trials.
In 2011, Sabbagh et al. (25) reported on an RCT (n=482) that compared NBI to conventional colonoscopy. A systematic review of RCTs was also performed. In both the trial and the systematic review, the authors concluded, NBI did not improve detection of colorectal polyps when compared to conventional colonoscopy.
In 2012, Nagorni et al. (26) conducted a meta-analysis of 11 randomized trials to determine whether NBI colonoscopy might be better for detection of colorectal polyps than white light colonoscopy (WLC). The authors concluded that they could not find convincing evidence that NBI is significantly better than high definition WLC for the detection of patients with colorectal polyps, or colorectal adenomas. They found evidence that NBI might be better than standard definition WLC and equal to high definition WLC for detection the patients with colorectal polyps, or colorectal adenomas.
In 2012, Dinesen et al. (27) reported on a meta-analysis of NBI compared to standard WLC for adenoma detection. The meta-analysis included 7 NBI studies, with a total of 2936 patients. The mail outcome measurement was adenoma and polyp detection rates and the number of polyps and adenomas detected per person. There was no statistically significant difference in the overall adenoma detection rate with the use of NBI or WLC (36% vs 34%; P = .413 [relative risk 1.06; 95% CI, 0.97-1.16]), and there was no statistically significant difference in polyp detection rate by using NBI or WLC (37% vs 35%; P = .289 [relative risk 1.22; 95% CI, 0.85-1.76]). When the number of adenomas and polyps per patient was analyzed, no significant difference was found between NBI and WLC (0.645 vs 0.59; P = .105 and 0.373 vs 0.348; P = .139 [weighted mean difference 0.19; 95% CI, ∞0.06 to 0.44], respectively). NBI did not increase adenoma or polyp detection rates.
Convincing evidence was not found that proved NBI is significantly better than high definition WLC for the detection of patients with colorectal polyps, or colorectal adenomas; some evidence was found that NBI might be better than standard definition WLC and equal to high definition WLC for detection the patients with colorectal polyps, or colorectal adenomas. The impact of this technology on health outcomes is not known, and no clinical trial publications or any additional information was found that would change the coverage position of this medical policy.
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ICD-9 Diagnosis Codes
Experimental, investigational and/or unproven for all diagnoses
ICD-9 Procedure Codes
ICD-10 Diagnosis Codes
Experimental, investigational and/or unproven for all diagnoses
ICD-10 Procedure Codes
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The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.
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2/15/2014 Document updated with literature review. Coverage unchanged. CPT/HCPCS code(s) updated. Title changed from “Fiberoptic Analysis of Colorectal Polyps” to “In Vivo Analysis of Colorectal Polyps”.
5/1/2008 Policy reviewed without literature review.
11/15/2006 Revised/updated entire document
8/15/2006 New medical document
|Title:||Effective Date:||End Date:|
|In-Vivo Analysis of Colorectal Polyps||06-15-2018||03-31-2019|
|In-Vivo Analysis of Colorectal Polyps||01-15-2018||06-14-2018|
|In-Vivo Analysis of Colorectal Polyps||02-01-2017||01-14-2018|
|In Vivo Analysis of Colorectal Polyps||08-15-2015||01-31-2017|
|In Vivo Analysis of Colorectal Polyps||02-15-2014||08-14-2015|
|Fiberoptic Analysis of Colorectal Polyps||05-01-2008||02-14-2014|
|Fiberoptic Analysis of Colorectal Polyps||11-15-2006||04-30-2008|
|Fiberoptic Analysis of Colorectal Polyps||08-15-2003||11-14-2006|