Pilot Study of a National Screening Programme for Bowel Cancer in Norway

Colorectal Cancer Screening in Norway: Pilot Study of a National Screening Programme With Randomised Comparison of Different Screening Strategies to Provide the Best Possible Service to the Population

The Norwegian government has funded a pilot study of a national colorectal cancer screening programme. This implies initiation of a screening pilot in the catchment area for two hospitals in Norway. The target population is average risk men and women at age 50-74 years. The programme is designed as a comparative effectiveness programme evaluating acceptance and test performance for two screening methods - fecal occult blood testing (FOBT) and flexible sigmoidoscopy (FS). This protocol describes the main methodological issues, necessary resources and the expected effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Colorectal Adenomas
• Intervention / Treatment: Procedure: Flexible sigmoidoscopy; Procedure: iFOBT

Detailed Description

There are several candidate screening modalities - fecal occult blood (FOBT), flexible sigmoidoscopy, colonoscopy, CT and MRI colonography and a range of molecular markers. Of these, only FOBT and FS have been subjected to long-term follow-up in randomised trials (RCTs). These two modalities will be tested in a head-to-head comparison by 1:1 randomisation. Previous studies have suggested that the attendance for FS may be lower than for FOBT. However, participation has been shown to decline with repetitive rounds required for FOBT, while infrequent or once-only screening may suffice for FS. A better test performance for FS makes it uncertain which method may be most beneficial in a public health perspective. This is the first time a national screening programme is designed as a platform for comparative effectiveness studies.

The pilot study will be carried out in two hospital catchment areas in South-East Norway - each with a target population of 70,000 men and women at 50-74 years of age - altogether 140,000 individuals to be randomised 1:1 between screening with an immunochemical test for faecal occult blood (iFOBT) biennially or FS once only. The primary endpoint is colorectal mortality reduction after 10 years. Attendance for FS is expected to be 50% and 60% for iFOBT. Expected CRC mortality reduction is 30% (286 CRC deaths) in the FS arm and 15% (143 CRC deaths) in the iFOBT arm (intention-to-treat). In a 1:1 randomisation with 80% statistical power and a significance level of 5% it will require 70,000 individuals in each arm to disclose a statistically significant difference between FS and iFOBT screening in an intention-to-treat model. We expect 5% in the iFOBTs group to test positive and require colonoscopy work-up. A positive FS is defined as 'any advanced neoplasia' (CRC, adenoma >10mm, adenoma with high-grade dysplasia or villous components). A finding of advanced neoplasia is expected in 5% of FS requiring full colonoscopy.

Study entry-date: All individuals were randomized to each of the two groups (iFOBT or sigmoidoscopy) before study start. Because first round screening of the iFOBT arm (70,000 invitees) will be finished in a shorter time frame compared to sigmoidoscopy, invitees in the flexible sigmoidoscopy arm are prone to more relevant time-dependent events between randomization and time of screening actually being offered. Therefore, primary entry-date was defined as day of mailed invitation in both screening groups. This approach means that the mean age at invitation in the sigmoidoscopy screening group will be older than in the iFOBT group, and analyses have to take this age-difference into account. Randomization date was chosen as a secondary study entry date to allow comparative analysis of effects of choosing the two entry date definitions. Sub-studies on lifestyle, psychological reactions comparing participants and control groups not invited to screening from neighbouring municipalities are performed. A randomized sub-study comparing various premedication in work-up colonoscopies is also performed.

Sub-studies

1. Changes in modifiable lifestyle factors such as not smoking, normal weight, high level of physical activity may reduce the risk of CRC. Correlation between these factors and endoscopic findings will be assessed. Limited intervention will be tested to improve life style.
2. The effect of screening on Psychological factors and the willingness to repeat screening will be assessed
3. Creation of a validated Sigmoidoscopy Bowel Preparation scale with subsequent testing of various bowel preparation modalities will be performed.
4. RCT with various strategies og analgesia during colonoscopy will be tested to improve patient experience.

• Study Type: Interventional
• Enrollment (Actual): 140000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 1535
    • Moss Hospital
  • Rud, Norway, 1309
    • Bærum County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• men and women
• age 50-74 years
• living in defined geographic areas in South-East Norway (catchment areas for two hospitals)

Exclusion Criteria:

• previous colorectal cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Flexible sigmoidoscopy; 70,000 men and women at age 50-74 years are randomised from the population registry to be invited to have a screening examination using flexible sigmoidoscopy once-only	Procedure: Flexible sigmoidoscopy; Flexible sigmoidoscopy screening is offered once only; Other Names: FlexSig= flexible sigmoidoscopy
EXPERIMENTAL: iFOBT; 70,000 men and women at age 50-74 years randomised from the population registry to be invited to have a screening examination biennially using an immunochemical test for fecal occult blood testing (iFOBT).	Procedure: iFOBT; Biennial screening with iFOBT; Other Names: iFOBT = immunochemical test for fecal occult blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
colorectal cancer mortality	colorectal cancer mortality after 10 years of follow-up, possibly extending to 15 years of follow-up	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colorectal cancer incidence	Colorectal cancer incidence after 10 years of follow-up, possibly extending to 15 years of follow-up	10 years
Complications and quality assurance	Both screening arms will be subject to continuous registration of complications and quality assurance measures of screening itself and work-up of screening positives	4 years
Psychological effects of screening	The level and duration of psychological reactions to screening (anxiety, quality of life) and influence on lifestyle (smoking, physical exercise, dietary habits) will be assessed during the first 4-5 active screening years of the study	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel preparation in Sigmoidoscopy	Improved strategy for bowel preparation	1 year start Fall 2017
Pain reduction during Colonoscopy	Test various strategies for analgesia during colonoscopy	18 months from Fall 2017

Collaborators and Investigators

• Sponsor: Cancer Registry of Norway
• Collaborators: University of Oslo
• Investigators: Study Director: Giske Ursin, MD, PhD, Cancer Registry of Norway, Oslo, Norway

Publications and helpful links

General Publications

• Schult AL, Botteri E, Hoff G, Holme O, Bretthauer M, Randel KR, Gulichsen EH, El-Safadi B, Barua I, Munck C, Nilsen LR, Svendsen HM, de Lange T. Women require routine opioids to prevent painful colonoscopies: a randomised controlled trial. Scand J Gastroenterol. 2021 Dec;56(12):1480-1489. doi: 10.1080/00365521.2021.1969683. Epub 2021 Sep 17.
• Kvaerner AS, Birkeland E, Bucher-Johannessen C, Vinberg E, Nordby JI, Kangas H, Bemanian V, Ellonen P, Botteri E, Natvig E, Rognes T, Hovig E, Lyle R, Ambur OH, de Vos WM, Bultman S, Hjartaker A, Landberg R, Song M, Blix HS, Ursin G, Randel KR, de Lange T, Hoff G, Holme O, Berstad P, Rounge TB. The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants. BMC Cancer. 2021 Aug 18;21(1):930. doi: 10.1186/s12885-021-08640-8.
• Schult AL, Botteri E, Hoff G, Randel KR, Dalen E, Eskeland SL, Holme O, de Lange T. Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study. BMJ Open. 2021 Jul 1;11(7):e048183. doi: 10.1136/bmjopen-2020-048183.
• Randel KR, Schult AL, Botteri E, Hoff G, Bretthauer M, Ursin G, Natvig E, Berstad P, Jorgensen A, Sandvei PK, Olsen ME, Frigstad SO, Darre-Naess O, Norvard ER, Bolstad N, Korner H, Wibe A, Wensaas KA, de Lange T, Holme O. Colorectal Cancer Screening With Repeated Fecal Immunochemical Test Versus Sigmoidoscopy: Baseline Results From a Randomized Trial. Gastroenterology. 2021 Mar;160(4):1085-1096.e5. doi: 10.1053/j.gastro.2020.11.037. Epub 2020 Nov 21.
• Randel KR, Botteri E, Romstad KMK, Frigstad SO, Bretthauer M, Hoff G, de Lange T, Holme O. Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening. Gastroenterology. 2019 May;156(6):1642-1649.e1. doi: 10.1053/j.gastro.2019.01.040. Epub 2019 Jan 25.
• Kirkoen B, Berstad P, Botteri E, Dalen E, Nilsen JA, Hoff G, de Lange T, Bernklev T. Acceptability of two colorectal cancer screening tests: pain as a key determinant in sigmoidoscopy. Endoscopy. 2017 Nov;49(11):1075-1086. doi: 10.1055/s-0043-117400. Epub 2017 Sep 22.
• Kirkoen B, Berstad P, Botteri E, Avitsland TL, Ossum AM, de Lange T, Hoff G, Bernklev T. Do no harm: no psychological harm from colorectal cancer screening. Br J Cancer. 2016 Mar 1;114(5):497-504. doi: 10.1038/bjc.2016.14. Epub 2016 Feb 11.

Helpful Links

• Web page for the study being translated into English

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2028
• Study Completion (ANTICIPATED): December 1, 2030

Study Registration Dates

• First Submitted: February 13, 2012
• First Submitted That Met QC Criteria: February 20, 2012
• First Posted (ESTIMATE): February 24, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: cancer; randomized trial; screening; adenoma; colon; rectum; iFOBT; flexible sigmoidoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenoma
• Other Study ID Numbers: CRCpilotNorway