Summary Of Evidence

Clinical Literature

The first-generation device had low sensitivity and specificity for polyps in the colon, however, a second-generation device received FDA clearance in January 2014 and expanded use in January 2016.^3,4 The improved design is slightly bigger with two cameras and an increased angle of view, allowing nearly 360-degree coverage of the colon. The capsule battery lasts 10 hours with a slower frame rate. Improvements in software allow estimation of polyp size and improved mucosal surface evaluation. Unless indicated, a reference to CCE is specific to the second-generation device. Both FDA indications are specific to colon polyp detection, but whereas the original restricted to use as a secondary procedure after failed OC, the expanded indication included use as a primary procedure in patients at major risk for colonoscopy or moderate sedation, and with evidence of lower GI bleeding.

The pivotal trial that led to FDA clearance was a prospective blinded study of 884 asymptomatic patients classified as average colorectal cancer (CRC) risk.⁵ Technical failures (short transit time plus poor preparation) occurred in 9% of patients. The authors conclude based on polyp detection sensitivity and specificity data that: “capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies.”

Two studies comparing CCE to CTC demonstrated at least non-inferiority in terms of sensitivity and specificity.^6,7 One found improved sensitivity and specificity for CCE, but both studies had methodological flaws with low-quality evidence. The advantages of CTC include the ability to use when obstruction or stricture is a concern and to obtain visualization of other abdominal structures. Advantages to CCE are the lack of radiation exposure and direct visualization of colorectal mucosa. Patient preference and availability of the technology also may play a role in test selection.

Several studies have shown that CCE sensitivity and specificity remain high in the detection of polyps in positive fecal occult blood test (FOBT) patients.^6,8,9 FOBT sensitivity for small adenomas is reported to be 7%, so the majority in these cases will not need a referral to OC if the CCE is adequate and negative.¹⁰ The authors generally conclude that in patients at high risk for OC or who have incomplete OC, CCE may be a reasonable alternative. Several studies included FOBT positive patients, among other indications (e.g., melena), but did not stratify results.^11-13

Rex et al.⁵ 2015, is a prospective blinded study of 884 patients classified as average risk. There were 695 of the 884 patients that underwent CCE followed by screening OC. According to the findings, “Capsule colonography identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI, 91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and 97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%-93%) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37% respectively, of false negative findings from capsule analyses” and resulted in one missed malignancy. In per segment analysis, right colon sensitivity was lower than left colon (72% compared to 88% respectively).

The study is strengthened by blinding, large sample size, and screening population. Study results may be impacted by allocation bias due to non-consecutive enrollment. Sessile serrated and hyperplastic polyps showed reduced sensitivity with CCE and this technology may not be reliable for detection. These types of polyps are also more difficult to detect on OC and CTC. There were no serious adverse events.

Rondonotti et al.⁶ 2014, is a pilot study of 50 patients with a positive immunochemical fecal occult blood test (iFOBT-positive) who underwent CCE, CTC and OC. According to the findings “CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. Pill Cam Colon2 identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ration, and a 0.06 negative likelihood ratio.” The study demonstrates performance of CCE in a population with fecal occult positive results. The study results may be impacted by the small sample size and high risk of bias. There were no serious adverse events.

Spada et al.⁷ 2015, is a prospective single-blinded study of 100 patients with a previous incomplete colonoscopy. There were 97 of 100 patients enrolled consecutively that underwent CCE and CTC on the same day. According to the findings, “CCE and CTC were able to achieve complete colonic evaluation in 98% of cases. In a per-patient analysis for polyps ≥6 mm, CCE detected 24 patients (24.5%) and CTC 12 patients (12.2%). The relative sensitivity of CCE compared to CTC was 2.0 (95% CI, 1.34 to 2.98), indicating a significant increase in sensitivity for lesions ≥6 mm. Of larger polyps (≥10 mm), these values were 5.1% for CCE and 3.1% for CTC (relative sensitivity: 1.67 (95% CI, 0.69 to 4.00)). Positive predictive values for polyps ≥6 mm and ≥10 mm were 96% and 85.7%, and 83.3% and 100% for CCE and CTC, respectively. No missed cancer occurred at clinical follow-up of a mean of 20 months.” The study demonstrates utility of the test in a population of patients with incomplete colonoscopies. Analysis demonstrates non-inferiority between CCE and CTC. The study is strengthened by a blinded cohort and consecutive enrollment. Patients received both studies for comparison purposes; however, if the results were negative OC was not performed so false negatives could not be excluded. There were no serious adverse events.

Holleran et al.⁸ 2014, is a comparative cohort study of 62 screening patients who had positive immune-chemical fecal occult blood tests. All the patients had complete studies with both CCE and OC. According to the findings, “Optical colonoscopy detected at least one polyp in 36 participants (58%), significant lesions in 18 (29%), and cancer in 1 (2%). There was good correlation between CCE and optical colonoscopy for any lesion and for significant lesions (r=0.62 and 0.84, respectively). The negative predictive value of CCE was high both for any polyp (90%) and for significant lesions (96%).”

Kobaek-Larsen et al.⁹ 2018, is a comparative cohort study of 253 patients who had positive iFOBT. There were 126 out of 253 patients that had complete studies with both CCE and OC. According to the findings “The polyp detection rate was significantly higher in CCE compared with colonoscopy (P=0.02) in the complete study group. The per-patient sensitivity for the entire population for >9 mm polyps for CCE and colonoscopy was 87% (95% CI: 83%-91%) and 88% (95% CI: 84%-92%) respectively.” “One malignancy was missed in the incomplete study group and was found on colonoscopy.” The study demonstrates performance of CCE in a population with fecal occult positive test results. The high rate of incomplete studies was attributed to the lack of booster in bowel prep. The study result may be impacted by small sample size and high risk of bias. There were two bowel perforations in the colonoscopy group.

Multiple international papers reported similar findings for sensitivity and specificity.^14-17 The completion rate was found to be lower than optical colonoscopy (OC), and incomplete studies (range from 0-46%) were more likely to miss malignancies.⁹ Colon Capsule Endoscopy (CCE) performance was less accurate than OC, confirming that OC remains the preferred testing modality.

A 2015 Health Quality Ontario meta-analysis on colon capsule endoscopy for the detection of colorectal polyps included five studies that evaluated CCE with a pooled total of 357 subjects.¹⁸ It found an 87% sensitivity and 76% specificity for 6 mm polyps and 89% sensitivity and 91% specificity for 10 mm polyps, which was described as good sensitivity and specificity. The analysis did not include papers published after 2014.

A 2016 meta-analysis with 2,420 subjects reported the following: for polyps > 6 mm: 86% (82%-89%) sensitivity and 88% (74%-95%) specificity. For polyps > 10 mm: 87% (81%-91%) sensitivity and 95% (92%-98%) specificity.¹⁹ The consistency in the findings among the studies over an eight-year period, and improved sample size and design in the more recent studies, improve the overall quality of the data from the earlier assessments. Limitations of the technology include poor sensitivity for sessile polyps and a high rate of incomplete studies.

Systematic Reviews

A 2018 Emergency Care Research Institute (ECRI) Technology assessment rates evidence as “somewhat favorable” and concludes: “Evidence from two systematic reviews indicates CCE can detect polyps in patients unable or unwilling to undergo colonoscopy or who had an incomplete colonoscopy”.²¹ Studies also indicate CCE related adverse events (AEs) are rare. The ECRI report also reviewed FDA MAUDE reports, which was consistent with the literature in terms of adverse events and safety profile; the most common complication is capsule retention.

The American Society for Gastrointestinal Endoscopy (ASGE) US Multi-Society Task Force (MSTF) on CRC recommends CCE as “an appropriate screening test when patients decline colonoscopy, FIT, FIT-fecal DNA, CTC, and flexible sigmoidoscopy” (weak recommendation, low-quality evidence).¹

Analysis of Evidence

Based on the clinical literature and systematic review results, combined with the consistent positive safety profile, sensitivity and specificity of CCE in detecting polyps ≥6 mm, the evidence supports the recommendation that CCE is an alternative to OC or CTC as a primary procedure in patients with major risks for OC or moderate sedation or as a secondary procedure for surveillance of colon polyp(s) in previously diagnosed patients where diagnostic OC was incomplete or was contraindicated. In addition, CCE may be useful as a secondary procedure when an incomplete diagnostic OC was performed for either fecal occult blood test (FOBT) positive (guaiac or immunochemical) for multi-target stool DNA (sDNA) test positive, or other evidence of lower GI bleeding in hemodynamically stable patients.

In 2021 the U.S. Preventive Services Task Force (USPSTF) expanded recommendations to include blood-based biomarker colorectal cancer screening test (CRC). CMS added blood-based biomarkers as a screening option per NCD 210.3 Screening for Colorectal Cancer Blood-Based Biomarker Test. While diagnostic colonoscopy would be standard of care for further evaluation in the event of a positive screening test, if that could not be performed as indicated in the coverage criteria, colon capsule endoscopy may be indicated therefore the coverage criteria was expanded to include blood-based biomarker CRC screening test.

Coverage Indications, Limitations and/or Medical Necessity

Compliance with the provisions in this policy may be monitored and addressed through post payment data analysis and subsequent medical review audits.

History/Background and/or General Information

Colon Capsule Endoscopy (CCE) is a noninvasive procedure that does not require air inflation or sedation and allows for minimally invasive and painless colonic evaluation. CCE utilizes a tiny wireless camera that takes pictures of the gastrointestinal tract. The wireless camera is housed inside a vitamin-size capsule that is swallowed with water. As the capsule travels through the digestive tract, the camera system takes pictures. The images are then transmitted to a computer with special software where the images are strung together to create a video. The provider reviews the video to look for any abnormalities within the gastrointestinal tract.

Definitions (U.S. Multisociety Taskforce)

Cancer Screening strategies refer to those measures taken to diagnose cancerous and pre-cancerous lesions in asymptomatic people with no previous history of such.¹

Cancer Diagnostic strategies refer to the measures taken to investigate persons with symptoms suspicious for malignancy or as a result of positive screening tests.¹

Cancer Surveillance refers to the interval utilization of diagnostic strategies in people with previously detected cancerous or pre-cancerous lesions.¹

Covered Indications

For diagnostic and/or surveillance purposes, Colon Capsule Endoscopy (CCE) is medically necessary when EITHER of the following criteria are met:

1. Primary procedure in patients with major risks for Optical Colonoscopy (OC) or moderate sedation as indicated from an evaluation of the patient by a board certified or board eligible gastroenterologist, a surgeon trained in endoscopy, or a physician with equivalent endoscopic training and EITHER of the following criteria are met²:
   
   • Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) OR
   • Multitarget Stool DNA (sDNA) Test positive OR
   • Blood-based biomarker colorectal cancer screening test (CRC) positive OR
   • Other evidence of lower GI bleeding in hemodynamically stable patients
2. Secondary procedure:
   • For the detection or surveillance of colon polyp(s) if the diagnostic OC was incomplete OR
   • When an incomplete diagnostic OC was performed for either:
   
   • Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) OR
   • Multitarget Stool DNA (sDNA) Test positive OR
   • Blood-based biomarker colorectal cancer screening test (CRC) positive OR
   • Other evidence of lower GI bleeding in hemodynamically stable patients

Limitations

The following are considered not medically reasonable and necessary:

1. Patients with known or suspected gastrointestinal obstruction, stricture, or fistula.
2. Patients with a cardiac pacemaker or another implanted electro-medical device that emits a radiofrequency or other interfering signal.
3. Patients with swallowing disorder(s).
4. Patients with a known contraindication or allergy to any medication or preparation agent used before or during the procedure.
5. May not be performed in conjunction with CT Colonography (CTC).
6. CCE is not a Medicare Benefit for colorectal cancer screening, regardless of family history or other risk factors for the development of colonic disease. Please refer to NCD 210.3 for colorectal cancer screening coverage.

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

The redetermination process may be utilized for consideration of services performed outside of the reasonable and necessary requirements in this LCD.