The Northern-European Initiative on Colorectal Cancer

Colorectal cancer (CRC) is a major burden in western countries. The disease develops from precursor lesions during a long time-interval. Colonoscopy can detect and remove CRC precursor lesions and may thus be effective for CRC prevention. Many national and international health organisations demand evidence from randomised trials to reduce incidence or mortality of the target disease before advocating population-wide cancer screening. However, while colonoscopy screening for the prevention of colorectal cancer is established in the United States and several European countries, no randomised trials exist to quantify the possible benefit of colonoscopy screening. NordICC is a randomised trial investigating the effect of colonoscopy on CRC incidence and mortality. NordICC is a multicentre, randomised trial in Nordic countries, the Netherlands and Poland. A minimum of 66 000 individuals, age 55-64 years, are drawn randomly from the population registries in the participating countries. 22 000 are invited for once-only colonoscopy (2:1 randomisation). Expected work-load with 50% compliance will be 11,000 colonoscopies. At the screening examination, all detected lesions are biopsied and removed whenever possible. The remaining 44 000 individuals (control group) are not offered any screening examination (care as usual).The primary study aims are CRC incidence and CRC mortality after 15 years of follow-up, with an interim analysis after 10 years of follow-up. In an intention-to-treat approach, a risk reduction of CRC mortality of 25% in the colonoscopy screening group compared to the control group is expected after 10 years follow-up, estimating 50% compliance in the screening group.

Sex

All

Minimum age

55 Years

Maximum age

64 Years

Inclusion Criteria:

* This study is a population-based randomised controlled trial, with randomisation of individuals age 55-64 years living in the screening areas directly from the Population Registries to either screening group or control group. Eligible persons with the same home address will be randomised to the same group (household randomisation).

Exclusion Criteria:

* Individuals with previous colorectal surgery (resections, enterostomies)
* Individuals in need of long-lasting attention and nursing services (somatic or psychosocial, mental retardation).
* On-going cytotoxic treatment or radiotherapy for malignant disease
* Severe chronic (longer than trial duration) cardiac (NYHA III-IV)or lung disease
* Lifelong anticoagulant therapy with Warfarin
* A coronary event requiring hospitalization during the last 3 months
* A cerebrovascular event during the last 3 months
* Resident abroad
* Return of unopened letter of invitation and/or reminder (address unknown)
* Message from neighbour/family/post office on death of screenee (not updated in Population Registry)

• DERIVEDKaminski MF, Kalager M, Loberg M, Emilsson L, Macios A, Samy F, Shi J, Fielding S, Hernan MA, Garborg K, Rupinski M, Dekker E, Spaander M, Holme O, Zauber AG, Pilonis ND, Didkowska J, Spychalski P, Hoff G, Regula J, Adami HO, Bretthauer M; NordICC Study Group*. Long-term effects of colonoscopy screening on colorectal cancer incidence and mortality: a multicountry, population-based randomised controlled trial. Lancet. 2026 May 9;407(10541):1787-1795. doi: 10.1016/S0140-6736(26)00508-8. Epub 2026 May 5. PMID 42102826
• DERIVEDBretthauer M, Loberg M, Wieszczy P, Kalager M, Emilsson L, Garborg K, Rupinski M, Dekker E, Spaander M, Bugajski M, Holme O, Zauber AG, Pilonis ND, Mroz A, Kuipers EJ, Shi J, Hernan MA, Adami HO, Regula J, Hoff G, Kaminski MF; NordICC Study Group. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. N Engl J Med. 2022 Oct 27;387(17):1547-1556. doi: 10.1056/NEJMoa2208375. Epub 2022 Oct 9. PMID 36214590
• DERIVEDShaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol. 2021 Mar 1;116(3):458-479. doi: 10.14309/ajg.0000000000001122. PMID 33657038
• DERIVEDBretthauer M, Kaminski MF, Loberg M, Zauber AG, Regula J, Kuipers EJ, Hernan MA, McFadden E, Sunde A, Kalager M, Dekker E, Lansdorp-Vogelaar I, Garborg K, Rupinski M, Spaander MC, Bugajski M, Hoie O, Stefansson T, Hoff G, Adami HO; Nordic-European Initiative on Colorectal Cancer (NordICC) Study Group. Population-Based Colonoscopy Screening for Colorectal Cancer: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):894-902. doi: 10.1001/jamainternmed.2016.0960. PMID 27214731
• DERIVEDPisera M, Kaminski MF, Kraszewska E, Rupinski M, Regula J. Reinvitation to screening colonoscopy: a randomized-controlled trial of reminding letter and invitation to educational meeting on attendance in nonresponders to initial invitation to screening colonoscopy (REINVITE). Eur J Gastroenterol Hepatol. 2016 May;28(5):538-42. doi: 10.1097/MEG.0000000000000578. PMID 26967693