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 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.

**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 met:2
    * Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) **OR**
    * Multitarget Stool DNA (sDNA) Test 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**
      * 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.
  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. When 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 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.

**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.

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.22 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 the 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).1

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.