**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:**

  1. 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
    1. Detection or surveillance of colon polyp(s) **OR**
    2. Diagnostic procedure when **ANY** of the following criteria are met (3):
      1. Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) **OR**
      2. Multitarget Stool DNA (sDNA) Test positive **OR**
      3. Blood-based biomarker colorectal cancer screening test positive **OR**
      4. Other evidence of lower GI bleed in hemodynamically stable patients
  2. 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:
    1. Surveillance of colon polyp(s) in previously diagnosed patients **OR**
    2. Diagnostic procedure when **ANY** of the following criteria are met (3):
      1. Fecal Occult Blood Test (FOBT) positive (guaiac or immunochemical) **OR**
      2. Multitarget Stool DNA (sDNA) Test positive **OR**
      3. Blood-based biomarker colorectal cancer screening test positive **OR**
      4. Other evidence of lower GI bleed in hemodynamically stable patients

**Exclusion Criteria (NONE of the below are allowed)**

  1. Known or suspected gastrointestinal obstruction, stricture, or fistula
  2. Cardiac pacemaker or another implanted electro-medical device if the CCE device is contraindicated due to emission of a radiofrequency or other interfering signal
  3. Swallowing disorder
  4. Known contraindication or allergy to any medication or preparation agent used before or during the procedure
  5. May not be done 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

* 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.

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.

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).