brand logo

Am Fam Physician. 2023;107(4):433-434

Clinical Question

Does an invitation to receive a colonoscopy reduce the incidence and mortality of colorectal cancer (CRC) compared with usual care?

Bottom Line

In the first randomized trial of CRC screening using colonoscopy, a smaller than expected reduction in CRC incidence was seen in the intention-to-treat (absolute risk reduction [ARR] = −0.22% over 10 years; number needed to invite = 455) and adjusted per-protocol analyses (ARR = −0.38%; P < .05; number needed to screen = 263). The same was true for reduction in CRC mortality in the intention-to-treat (ARR = −0.03%; P = not significant) and per-protocol analyses (ARR = −0.15%; P < .05). The lower than expected mortality reduction may be explained in part by improvements in treatment and the modest duration of follow-up. The authors were careful to adjust for differences between invitees who accepted colonoscopy and those who did not (to avoid the healthy volunteer bias), although unmeasured confounding is still possible. Trials comparing fecal immunochemical tests with colonoscopy are nearing their conclusion, and the results may add further clarity. (Level of Evidence = 1b)


Despite widespread use as a screening test for CRC in the United States, colonoscopy has never been subjected to a randomized trial. The authors identified 94,959 healthy men and women, 55 to 64 years of age, from the Netherlands, Norway, Sweden, and Poland who had not been screened for CRC in the past. The regions from which the participants were recruited did not have organized programs for CRC screening using colonoscopy. Follow-up data for 10,374 Dutch participants could not be included because of changes in European data protection laws that made it impossible to obtain data for uninvited people from the general population. The remaining 84,585 participants were randomized in a 1:2 ratio to receive an invitation for a single screening colonoscopy or usual care. The median age at enrollment was 59 years, one-half of the participants were women, and most came from Poland or Norway. Colonoscopy was performed at dedicated centers with training and quality assurance programs.

Only 11,843 (42%) of the 28,220 people invited to screening underwent colonoscopy. The median follow-up was 10 years, 91% had a good or very good bowel preparation, 97% achieved intubation of the cecum, and 30.7% had an adenoma detected. The risk of CRC was higher in the screened group for the first five years after colonoscopy, presumably because of cancer diagnoses during the examinations and heightened surveillance for precancerous lesions, but was less likely thereafter. In the intention-to-treat analysis, the incidence of CRC was significantly lower in the screened group (0.98% vs. 1.20%; relative risk [RR] = 0.82; 95% CI, 0.70 to 0.93; number needed to invite = 455 over 10 years). CRC mortality was not significantly lower in the screened group (0.28% vs. 0.31%; RR = 0.9; 95% CI, 0.64 to 1.16). There was no difference in all-cause mortality (11.03% vs. 11.04%). The authors performed a separate per-protocol analysis to estimate the benefits if everyone that was invited to receive a colonoscopy had been screened, adjusting for baseline differences between those accepting the invitation and those who ignored it (it is important to at least partially adjust for the healthy volunteer bias). They estimated a lower incidence of CRC (0.84% vs. 1.22%; RR = 0.69; 95% CI, 0.55 to 0.83; number needed to screen = 263) and a greater reduction in CRC mortality (0.15% vs. 0.30%; RR = 0.50; 95% CI, 0.27 to 0.77; number needed to screen = 667). Complications were rare; there were 15 episodes of major bleeding (0.13%; none were fatal) and no perforations.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Population-based

Reference: Bretthauer M, Løberg M, Wieszczy P, et al.; NordICC Study Group. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med. 2022;387(17):1547-1556.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.

Already a member/subscriber?  Log In


From $145
  • Immediate, unlimited access to all AFP content
  • More than 130 CME credits/year
  • AAFP app access
  • Print delivery available

Issue Access

  • Immediate, unlimited access to this issue's content
  • CME credits
  • AAFP app access
  • Print delivery available
Purchase Access:  Learn More

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to

This series is coordinated by Natasha Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at

Continue Reading

More in AFP

More in Pubmed

Copyright © 2023 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.