Short summary

Background: Colorectal cancer screening reduces mortality through early detection and prevention. However, the current Danish program is limited by a low sensitivity of the immunochemical faecal occult blood test (IFOBT), low acceptance in the population and missed pathology at colonoscopy. Further, the burden of the program on endoscopy units and society costs are substantial. Colon capsule endoscopy (CCE), where a swallowed capsule video records the colonic mucosa is a new and promising technique for non-invasive detection of polyps and cancer in colon.

Aim: To investigate the performance of CCE compared to colonoscopy and the clinical impact of an alternative screening protocol of first CCE and if positive subsequent colonoscopy in IFOBT positive individuals.

Design and method: 250 IFOBT positive patients undergo both CCE and subsequent colonoscopy with blinded investigators to determine sensitivity and specificity. Patients complete questionnaires to determine their experience with the exams.

Perspectives: The study will add vital information to the possible use of the less invasive procedure of CCE in the screening of colorectal cancer in order to increase participation and reduce per patient burden on the health care system without changing the clinical outcome.

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Rationale

Background:

The population based screening for colorectal cancer was initiated in Denmark in April 2014, in order to promote the finding and treatment of more and earlier neoplasm. Individuals aged 55-74 years are invited to participate and asked to return an immunochemical fecal occult blood test (IFOBT), and if positive, the patient is invited to a colonoscopy. Those with cancer will be operated and withdrawn from the screening program. Those with benign lesions and normal findings will continue the program according to their risk of developing cancer. The screening outcomes are:

Normal: Reentering into the screening program after 8 years

Low risk: Less than 3 adenomas (tubular), all under 10 mm in diameter and with low grade dysplasia will be invited for a re- screening within 2 years.

Medium risk: 3-4 adenomas or one adenoma of 10-20 mm in diameter or a villous component or high grade dysplasia in any of the adenomas removed. Repeated colonoscopy within 3 years.

High risk: 5 adenomas or more, one adenoma larger than 20 mm or an adenoma removed with piece-meal technique. Repeated colonoscopy within 1 year.

However, the screening program has several limitations. The present participation in the Danish program is 58 % and only 84 % with a positive IFOBT accept the offered colonoscopy. A single IFOBT with cut-off of 100 ng/ml, as used in Denmark, has a sensitivity of 61.5% to adenomas larger than 1 cm and cancers resulting in many false negatives and therefore the screening are repeated biannually. Colonoscopy is not an ideal procedure; only 88 % being complete due to long or tortuous colon, pain or unsatisfactory cleansing and 5% of polyps over 1 cm and 25 % of polyps below 5 mm are missed. Further, the program is a substantial burden for endoscopy and pathology units. Despite these limitations the screening has a positive effect on survival from colorectal cancer.

Colon Capsule Endoscopy (CCE) is a new technology that may have the potential to complement the existing screening program. The procedure is less invasive compared to colonoscopy with fewer complications and less discomfort for the patient rendering a similar overview of the colorectal mucosa as colonoscopy. The second generation colonic capsule has demonstrated a sensitivity of 88% and specificity of 95% of neoplasias >9 mm in diameter in persons with symptoms and with colonoscopy (sensitivity of 90%) as the golden standard. Therefore the true accuracy of CCE is potentially comparable to colonoscopy. Currently there is no study investigating the potential of CCE in a screening population. 

Hypothesis:

CCE has a clinical accuracy in identifying low, medium, high risk and cancer patients comparable to colonoscopy in an IFOBT positive screening population.

A three step screening program, where a positive IFOBT is followed by first CCE and when positive a colonoscopy will identify as many medium, high risk and cancer patients as the regular screening program of IFOBT followed by colonoscopy and reduce the number of colonoscopies with 60-75 %.

The patient related stress and anxiety towards CCE is lower than colonoscopy, which could improve screening participation if implemented    

Aim:

To determine the sensitivity, specificity, LR-ratio and ROC curves of CCE and colonoscopy in risk stratification, adenoma amount and size in IFOBT positive screening patients undergoing both procedures.

To determine the inter and intra-observer variability of pathology detection of CCE video analysis

To estimate the patient related stress and anxiety towards CCE and colonoscopy

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Description of the cohort

255 IFOBT positive individuals will be recruited by letter of invitation from the national screening programme on the island of Funen. 

Data and biological material

The data collected includes individual demographics of gender and age, examination reports on quality, findings and complications of the two exams as well as questionaires regarding examination experience.

Collaborating researchers and departments

Department of Surgery, Odense University Hospital

• PhD-student Rasmus Krøijer

Department of Surgery, Odense University Hospital, Svendborg

• PhD-student Marleen Buijs

Department of Surgery, Odense University Hospital, Odense and Institute of Clinical Research, University of Southern Denmark

• Professor and consultant Niels Qvist

Department of Surgery, Odense University Hospital, Svendborg and nstitute of Regional Health Services, University of Southern Denmark

• Professor and consultant Gunnar Baatrup

Department of Surgery, Odense University Hospital and Forskningsenheden, Odense Universitets hospital, Svendborg

• Postdoc Morten Kobæk Larsen, PhD