CMS Colon Capsule Endoscopy (CCE) Form
This procedure is not covered
Background for this Policy
Summary Of Evidence
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 takes pictures that are transmitted to a recorder worn by the patient. 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.
The first-generation device had a low sensitivity and specificity for polyps in the colon, however a second-generation device received FDA clearance January 2014 and expanded use in January 2016 (1,2). The improved design is slightly bigger with two cameras and increased angle of view allowing nearly 360-degree coverage of the colon. The capsule battery last 10 hours with a slower frame rate. Improvements in software allow estimation of polyp size and improved mucosal surface evaluation. Unless indicated, 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. See Table 1 for details of the following studies.
The pivotal trial that led to FDA clearance was a prospective blinded study of 884 asymptomatic patients classified as average colorectal cancer (CRC) risk (4). 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 (5,6). One found improved sensitivity and specificity for CCE, but both studies had methodological flaws with low quality evidence. Advantages to 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 detection of polyps in positive fecal occult blood test (FOBT) patients (5,7,8). FOBT sensitivity for small adenomas is reported to be 7% so the majority in these cases will not need referral to OC if the CEE is adequate and negative (9). The authors generally conclude that in patients at high risk for OC, or who have incomplete OC, CCE may be reasonable alternative. Several studies included FOBT positive patients, among other indications (e.g., melena), but did not stratify results (10-12).
Table 1 Clinical Literature
| Study | Protocol | Findings | Assessment |
| Rex (2015) Accuracy of Capsule Colonoscopy in Detecting Colorectal Polyps in a Screening Population (4) | Prospective blinded study of 884 asymptomatic patients classified as average risk. 695/884 patients underwent CCE followed by screening OC. | "Capsule colonoscopy 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). | Study 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 CEE and this technology may not reliable for detection. These types of polyps are also more difficult to detect on OC and CTC. No serious adverse events. |
| Rondonotti (2014) Accuracy of Capsule Colonoscopy and Computed Tomographic Colonography in Individuals With Positive Results From the Fecal Occult Blood Test (5) | Pilot study of 50 patients with a positive immunochemical fecal occult blood test (iFOBT-positive). 50 patients underwent CCE, CTC and OC | "CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. CCE identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ratio, and a 0.06 negative likelihood ratio." | Demonstrates performance of CCE in population with fecal occult positive test results. Study results may be impacted by small sample size and high risk of bias. No serious adverse events. |
| Spada (2015) Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial (6) | Prospective single-blinded cohort study of 100 patients with a previous incomplete colonoscopy. 97/100 patients were enrolled consecutively underwent CCE and CTC on the same day. | "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." | Demonstrates utility of test in population with incomplete colonoscopy. Analysis demonstrates non-inferiority between CCE and CTC. Study strengthened by blinded cohort and consecutive enrollment. Patients received both studies for comparison, but if results negative did not have OC so could not exclude false negatives. No serious adverse events. |
| Holleran (2013) Colon capsule endoscopy as possible filter test for colonoscopy selection in a screening population with positive fecal immunology (7) | Comparative cohort study of 62 screening patients who had a positive immune-chemical fecal occult blood test. All patients had complete studies with both CCE and OC | "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 (2018) Back-to-back colon capsule endoscopy and optical colonoscopy in colorectal cancer screening individuals (8) | Comparative cohort study of 253 patients who had a positive iFOBT. 126/253 patients had complete studies with both CCE and OC | “There were 253 participants. 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 entire population for > 9 mm polyps for CCE and colonoscopy was 87% (95% CI: 83–91%) and 88% (95% CI: 84–92%) respectively.” 1 malignancy was missed in incomplete study group and found on colonoscopy." | Demonstrates performance of CCE in population with fecal occult positive test results. The high rate of incomplete studies were attributed to lack of booster in bowel prep. Study results may be impacted by small sample size and high risk of bias. 2 bowel perforation in colonoscopy group. |
Multiple international papers reported similar findings for sensitivity and specificity (13-16). Completion rate was found to be lower than optical colonoscopy (OC) and incomplete studies (range from 0-46%) were more likely to miss malignancies (8). CCE performance was less accurate than OC confirming that it remains the preferred testing modality.
Analysis of Evidence
A 2015 Health Quality Ontario meta-analysis on colon capsule endoscopy for the detection of colorectal polyps included five studies which evaluated CCE with a pooled total of 357 subjects (17). It found a 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. See Table 2 for details.
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 (18). 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 high rate of incomplete studies. See Table 2 for details.
Table 2 Systematic Reviews
| Review | Purpose | Findings | Assessment |
| Health Quality Ontario (2015)- Colon Capsule Endoscopy for the Detection of Colorectal Polyps: An Evidence-Based Analysis (17) | “To evaluate the diagnostic accuracy and safety of colon capsule endoscopy for the detection of colorectal polyps among adult patients with signs or symptoms of colorectal cancer or with increased risk of colorectal cancer, and to compare colon capsule endoscopy with alternative procedures.” | “Colon capsule endoscopy, using PCC2, had a pooled sensitivity and specificity of 87% (95% confidence interval [CI] 77%-93%) and 76% (95% CI 60%-87%), respectively, for the detection of a colorectal polyp at least 6 mm in size (GRADE: very low). PCC2 had a pooled sensitivity and specificity of 89% (95% CI 77%-95%) and 91% (95% CI 86%-95%), respectively, for the detection of a colorectal polyp at least 10 mm in size (GRADE: low). One study directly compared PCC2 with computed tomographic (CT) colonography and found no statistically significant difference in accuracy (GRADE: low). Few adverse events were reported with PCC2; 3.9% of patients (95% CI 2.4%-6.5%) experienced adverse effects related to bowel preparation. Capsule retention was the most serious adverse event and occurred in 0.8% of patients (95% CI 0.2%-2.4%) (GRADE: very low).” | 5 studies evaluated ECC-2. All studies had small sample size (range 24-117). There is greater heterogeneity in the ≥6mm polyp group as compare to ≥ 10mm group. Studies were downgraded for methodological concerns including lack of randomization or consecutive enrollment and risk of bias. No serious adverse events. Need for additional studies identified. |
| Spada (2016) Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis (18) | To evaluate the accuracy of colon capsule endoscopy (CCE) in detection of colorectal polyps. | “Fourteen studies provided data from 2420 patients (1128 for CCE1 [CCE with PCC1] and 1292 for CCE2 [CCE with PCC2]). CCE2 [CCE with PCC2] and CCE1 [CCE with PCC1] detected polyps >6 mm with 86% sensitivity (95% CI, 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE2 and CCE1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE2 identified all 11 invasive cancers detected by colonoscopy.” | 1292 subjects included for evaluation of CCE2 using colonoscopy with histology as comparison in all series. Heterogeneity was high among the 14 trials and on further analysis an outlier study that evaluated CCE1 only was removed which reduced the amount of heterogeneity from 86.1% to 31.5% (p=0.109). No serious adverse events. Conclusion was device is less sensitive than colonoscopy especially for small polyps (≥ 6mm), but has good specificity for large polpys (≥ 8mm). |
These systematic review results, combined with the consistent positive safety profile, has led several organizations to consider the CCE a suitable alternative to CTC for incomplete colonoscopy. The European Society of Gastrointestinal Endoscopy (ESGE) considers CCE a reasonable alternative to screening colonoscopy in low cancer risk patients. The Canadian Clinical Practice Guidelines for the Use of Video Capsule endoscopy consensus statement recommends against the routine substitution of CCE for colonoscopy (GRADE: Strong recommendation, low quality evidence), however “In cases in which previous colonoscopy was incomplete or for patient who are unwilling/unable to undergo colonoscopy, CCE has shown to be a reasonable alternative (19).
A 2018 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” (20). Studies also indicate CCE related adverse events (AEs) are rare. The ECRI report also reviewed FDA MAUDE reports, which was consistent with literature in terms of adverse events and safety profile; the most common complication is capsule retention.
A 2019 Hayes technology assessment assigns CCE a “C” rating for use in diagnosis and surveillance of adults with signs or symptoms of colorectal cancer and risk factors for the disease (21). It concludes: “CCE may be a suitable alternative for patients who cannot tolerate or refuse to undergo conventional colonoscopy (CC) and for patients with an incomplete CC.” The rating was downgraded due to paucity of evidence regarding clinical utility of CCE for this indication. The report calls for further studies to determine the accuracy of CCE verses CTC.
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) (22).
In summary, the evidence supports the recommendation that CCE may be a suitable alternative to OC or CTC in a very select group of patients for whom a diagnostic OC for suspected polyps was either unsuccessful or relatively contraindicated. Ideally, CCE is performed after incomplete colonoscopy (if adequate preparation) to avoid the need for repeat bowel preparation (23).
Diagnostic and/or surveillance* (performed for signs/symptoms of disease) colon capsule colonoscopy (CCE) is medically necessary for the detection of colon polyps when EITHER of the following criteria are met:
- Secondary procedure after an incomplete diagnostic optical colonoscopy (OC) with adequate preparation, and a complete evaluation of the colon was not technically possible (1,2) when EITHER of the following criteria are met
- Detection or surveillance of colon polyp(s) OR
- Diagnostic procedure when ANY of the following criteria are met (3):
- Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) OR
- Multitarget Stool DNA (sDNA) Test positive OR
- Other evidence of lower GI bleed in hemodynamically stable patients
- Primary procedure in patients with major risks for 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 when EITHER of the following criteria are met:
- Surveillance of colon polyp(s) in previously diagnosed patients OR
- Diagnostic procedure when ANY of the following criteria are met (3):
- Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) OR
- Multitarget Stool DNA (sDNA) Test positive OR
- Other evidence of lower GI bleed in hemodynamically stable patients
Exclusion Criteria (NONE of the below are allowed)
- Known or suspected gastrointestinal obstruction, stricture, or fistula
- Cardiac pacemaker or another implanted electro-medical device if the CCE device is contraindicated due to emission of a radiofrequency or other interfering signal
- Swallowing disorder
- Known contraindication or allergy to any medication or preparation agent used before or during the procedure
- May not be done in conjunction with CT Colonography (CTC)
- CCE is not a Medicare Benefit for colorectal cancer screening, regardless of family history or other risk factors for the development of colonic disease
* Cancer Diagnostic strategies refer to the measures taken to investigate persons with symptoms suspicious for malignancy or as a result of positive screening tests. Cancer Surveillance refers to the interval utilization of diagnostic strategies in people with previously detected cancerous or pre-cancerous lesions. Cancer Screening strategies refer to those measures taken to diagnose cancerous and pre-cancerous lesions in asymptomatic people with no previous history of such.