Colon Capsule Endoscopy

National screening programmes face significant challenges in attempting to deliver timely and cost-effective screening. Bowel Screen is a two-stage population based programme that currently offers free bowel screening to men and women aged 60-69 years in Ireland. National colonoscopy capacity has been a rate limiting step in expansion of this programme to those aged 55-74 years. Patient acceptance of colonoscopy as a screening tool is also low with uptake as low at 11% in certain subgroups of invitees.10 Effective, alternative screening pathways are required.

To date, CCE is playing a marginal role in screening but there is a growing body of evidence supporting its use. A recent systematic review of its use in a screening population by Vuik et al included 13 studies, comprising 2485 patients.11 Eight studies used CCE as a filter test after a positive FIT result and five studies used CCE for primary screening. The polyp detection rate of CCE was 24 % – 74 %. For polyps > 6 mm, sensitivity of CCE was 79 % – 96 % and specificity was 66 % – 97 %. For polyps ≥ 10 mm, sensitivity of CCE was 84 % – 97 %, which was superior to CTC. The CRC detection rate for completed CCEs was 93 %. They concluded that the accuracy of CCE was comparable to colonoscopy and superior to CTC, making it a good alternative for screening programmes. A more recent meta-analysis by Kjolhede et al comparing CCE and colonoscopy with regards to polyp detection concluded that CCE did show high sensitivity and specificity for per-patients polyps compared to colonoscopy.12 CCE does perform well with regards to cancer detection.8, 13-16 In two studies, however, cancers were missed in the left colon due to the capsule battery dying and the capsule not viewing these areas.17, 18 There remains limited data regarding the ability of both CCE and CTC to detect laterally spreading tumours (LSTs) with good sensitivity and specificity.21,22 These non-polypoid lesions are also more difficult to pick up at traditional colonoscopy. CCE had a sensitivity of 0.86 for non-polypoid tumours in one review.21

Incomplete colonoscopies

Incomplete colonoscopies can occur in up 20% of patients and are associated with higher rates of missed lesions.23, 24 Reasons for incomplete colonoscopy include female gender, elder patients, long, redundant sigmoid colons, excessive looping, patient discomfort and a history of previous abdomino-pelvic surgeries.24, 25, 26 Four prospective studies have looked specifically at this group, with large number of polyps identified by CCE-2 in areas not reached by initial colonoscopy.27, 28, 29, 30 ESGE guidance now endorses the use of CCE in this situation.9

A prospective, single-centre, randomized trial, the VICOCA study, compared CCE and CTC in 290 individuals, using colonoscopy as the gold standard.31 It reported sensitivity, specificity and positive and negative predictive values of CCE for the detection of patients with any neoplastic lesion of 98.1%, 76.6%, 93.7% and 92.0%, respectively. CTC had sensitivity, specificity and positive and negative predictive values of 64.9%, 95.7%, 96.8% and 57.7%, respectively. In terms of detection of polyps > 6mm, the sensitivity of CCE and CTC was 96.1% and 79.3%. CCE was shown have superior sensitivity for detecting serrated lesions (73.6% versus 32.9%; p < 0.001). Similarly the TOPAZ trial concluded that CCE should be considered comparable, if not superior, to CTC as a screening test.32

Preparation is of particular interest in CCE given there is no opportunity to flush the mucosa or suction as with colonoscopy, and adequate propulsion is required to ensure the capsule is excreted prior to the battery dying. The quality of the protocol is dependent on many factors including the laxative used, timing and volume of laxative, types of boosters used and timing of boosters and also patient tolerability. Great variation exists between studies with regards to excretion rates and bowel cleanliness. A recent meta-analysis found that excretion rates varied from 57%- 100% and adequate bowel prep ranged from 40%-100% and concluded that improvements are needed in both areas before widespread implementation of CCE into surveillance programmes.12 Low -volume PEG preparations, sodium phosphate free boosters, prokinetics and suppositories are now used with good success, reducing the volume of fluid the patients have to ingest without compromising polyp detection.33, 34 Prucalopride has been recently shown to improve CCE completion rates and polyp detection rates, as has castor oil.35, 36, 37, 38

CCE is a safe procedure with the main consideration being capsule retention. The majority of the studies to date report no preparation or capsule related adverse events.11, 12, 13, 39, 40, 41 Adverse events reported are generally due to the preparation and include nausea, vomiting or bloating.15, 16, 18, 20, 33 Baltes described one retained capsule in the ileum in a patient who subsequently had it removed during resection for previously unknown Crohn’s disease.27

Capsule aspiration is a rare but documented complication which may occur in 0.1% of cases.42

Patient preference

CCE does appear to be more acceptable than colonoscopy.40, 43, 44, 45 A recent interim analysis asked over 14,000 participants in a screening programme (prior to their FIT result) whether they would prefer CCE or colonoscopy, with 50% choosing CCE versus 9% choosing colonoscopy.46 Disadvantages reported include longer wait time for results and unfamiliarity with the technology.43

Cost

An up-to-date analysis of cost effectiveness is needed. Recent ESGE guidance advised that CCE may be cost effective if it improves engagement in surveillance programmes.9 Hassan et al also concluded that CCEs effect on cost of screening lies it in ability to improve compliance.47

Future for CCE

CCE has been demonstrated to be comparable to traditional colonoscopy and better than CTC for detection of colonic pathology.12 In comparative studies it has been shown to be useful in both symptomatic participants and after incomplete colonoscopy. It is not without drawbacks, however, and certain areas, including bowel preparation as previously described, require particular attention.

A large proportion of those who undergo CCE still require follow up with colonoscopy or sigmoidoscopy.44 Reasons for this include need for polypectomy, inadequate views of the mucosa or the battery dying before being excreted. Along with improving bowel preparation regimens and battery life, the use of FIT testing as a triage tool could help reduce this burden. The optimum FIT level at which referral directly to CCE would be appropriate is yet to be determined.

The reading of colon capsules is time consuming and currently a rate limiting step in the expansion of capsule services in hospitals. Vuik et al reported a median time of 55 minutes for colon capsule reading.48 The combination of advances in artificial intelligence (AI) technologies, commercial interest and a growing body of supporting evidence suggests that the use of AI to augment day to day endoscopy will become a reality in the near future. AI software for colon capsules is currently in its infancy. It should help greatly with regards to polyp detection and also in speeding up reading.

Outside of polyp detection and screening, there is also a growing body of evidence for the use of CCE in inflammatory bowel disease (IBD) which is to be further explored. ESGE recent 2020 guidance advises there is currently insufficient data to support use of CCE in diagnosis or surveillance of those with suspected or known IBD, however noted current preliminary data suggests it may of use in monitoring of disease activity in UC.9

Now the accuracy of CCE has been established, investment in training and artificial intelligence, along with continued robust data regarding efficacy are necessary to ensure CCE finds its place in routine clinical practice. Large scale initiatives, like the use of CCE in the National Health Service (NHS) UK urgent cancer pathway, will provide a wealth of further information in the coming months and years.44 Despite drawbacks, CCE is a viable diagnostic alternative to colonoscopy at an important time in service delivery. The increasing demand on colonoscopy waiting lists raises valid concerns regarding the ability of health services to deliver endoscopy in a timely fashion. It is clear that alternative diagnostic and surveillance modalities are necessary and that CCE has a central role to play.49

References available on request