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-
sized 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.

**Covered Indications**

Diagnostic/surveillance, when performed for signs and symptoms of disease 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 when **EITHER**
of the following criteria are met3:

  *     * 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 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. CCE performed in conjunction with Computed Tomographic Colonography (CTC)
  6. CCE performed for screening, regardless of family history or other risk factors for the development of colonic disease

**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 NCDs, 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**

PillCamTM COLON 2 is a capsule endoscopy device. The first-generation device
had low sensitivity and specificity for polyps in the colon, however, a
second-generation device received United States (U.S.) Food and Drug
Administration (FDA) clearance in January 2014 and expanded use in January
2016.1,2 The improved design is slightly bigger with 2 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 was 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.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. 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 FOBT patients.5,7,8 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.9 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.10-12

Rex, et al.4 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 1 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.5 2014, is a pilot study of 50 patients with a positive
immunochemical fecal occult blood tests (iFOBTs-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. PillCamTM COLON 2 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.6 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.7 2014, is a comparative cohort study of 62 screening patients
who had positive iFOBTs. All the patients had complete studies with both CCE
and OC. According to the findings, "OC detected at least 1 polyp in 36
participants (58%), significant lesions in 18 (29%), and cancer in 1 (2%).
There was good correlation between CCE and OC 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.8 2018, is a comparative cohort study of 253 patients who
had positive iFOBTs. 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 2 bowel perforations in the colonoscopy group.

Multiple international papers reported similar findings for sensitivity and
specificity.13-16 The completion rate was found to be lower than OC, and
incomplete studies (range from 0-46%) were more likely to miss malignancies.8
CCE performance was less accurate than OC, confirming that OC remains the
preferred testing modality.

A 2015 Health Quality Ontario meta-analysis on CCE for the detection of
colorectal polyps included 5 studies that evaluated CCE with a pooled total of
357 subjects.17 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.18 The consistency
in the findings among the studies over an 8-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 ECRI Technology assessment rates evidence as "somewhat favorable" and
concludes: "Evidence from 2 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 Manufacturer and User
Facility Device Experience (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.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 the clinical
utility of CCE for this indication. The report calls for further studies to
determine the accuracy of CCE versus CTC.

The American Society for Gastrointestinal Endoscopy (ASGE) U.S. Multi-Society
Task Force (MSTF) on CRC recommends CCE as "an appropriate screening test when
patients decline colonoscopy, fecal immunochemical test (FIT), FIT-fecal DNA,
CTC, and flexible sigmoidoscopy" (weak recommendation, low-quality
evidence).22

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.