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evident
Original paper
2022NEJMPreventive/Primary Care

NordICC

Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death

RCTCancer screening

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Overview

Invitation to one screening colonoscopy lowered 10-year colorectal cancer incidence on intention-to-screen analysis but not colorectal cancer death.

Clinical takeaway

An invitation to one colonoscopy reduced 10-year colorectal cancer risk in intention-to-screen analysis. Colorectal cancer death and all-cause death were not lower. Only 42% of invited participants were screened, so this is the effect of invitation, not of colonoscopy in everyone who is scoped.

Key result

Intention-to-screen 10-year colorectal cancer risk was 0.98% in the invited group versus 1.20% with usual care (RR 0.82; 95% CI 0.70-0.93).

Practice impact

Cite NordICC as the effect of inviting average-risk adults to one colonoscopy, not as proof that colonoscopy itself fails.

Evidence

Study design

Pragmatic randomized trial of invitation to a single screening colonoscopy versus no invitation or screening. Reported results are intention-to-screen analyses.

Enrollment

84,585

Follow-up

Median follow-up of 10 years.

Geography

Poland, Norway, Sweden, the Netherlands

Clinical question

Does inviting adults 55 to 64 years of age to a single screening colonoscopy lower the risks of colorectal cancer and related death?

Population

  • Presumptively healthy men and women 55 to 64 years of age drawn from population registries.

Intervention

Invitation to undergo a single screening colonoscopy.

Comparator

No invitation or screening (usual care).

Primary outcome

Risks of colorectal cancer and related death. Death from any cause was a secondary end point.

Invitation to screening lowered 10-year colorectal cancer risk. The other primary end point, colorectal cancer death, was not lower (RR 0.90; 95% CI 0.64-1.16).

Risk ratio / 0.82 / 95% CI 0.70-0.93

Key results

  • Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden: 28,220 invited (11,843, or 42.0%, underwent screening) and 56,365 usual care. Participants were also drawn from the Netherlands; that country is not in this follow-up set.
  • Intention-to-screen colorectal cancer at 10 years: 0.98% invited versus 1.20% usual care (18% risk reduction; RR 0.82; 95% CI 0.70-0.93). Raw counts were 259 versus 622 cases. Number needed to invite to prevent one case: 455 (95% CI 270-1429).
  • Intention-to-screen colorectal cancer death: 0.28% versus 0.31% (RR 0.90; 95% CI 0.64-1.16).
  • Secondary end point, death from any cause: 11.03% versus 11.04% (RR 0.99; 95% CI 0.96-1.04).

Harms

  • Fifteen participants had major bleeding after polyp removal.
  • No perforations or screening-related deaths occurred within 30 days after colonoscopy.

Clinical Use

Practice impact

  • An invitation to one colonoscopy reduced 10-year colorectal cancer incidence in this population-registry trial.
  • Do not tell patients that screening colonoscopy failed to prevent cancer death; the death interval included no effect, and only 42% of those invited were screened.

Applicability

  • Average-risk adults 55 to 64 years of age in settings like the enrolled northern and central European registries, where many invitees may not attend.

Limitations

  • Enrollment of 84,585 is the cohort with follow-up in Poland, Norway, and Sweden, not a separately stated randomized N that includes the Netherlands.
  • This abstract reports intention-to-screen analyses only. Per-protocol (adjusted-for-participation) estimates are not given.
  • Median follow-up is 10 years; colorectal cancer death may need longer follow-up.
  • Uptake in the invited group was 42.0%.

Common misinterpretations

  • These numbers are intention-to-screen, not the effect of actually undergoing colonoscopy.
  • Colorectal cancer death was not reduced; the interval was 0.64 to 1.16.
  • All-cause death was not reduced.
  • Low uptake dilutes the invitation effect; this is not a trial of colonoscopy in a fully screened cohort.

Related evidence

PLCO - Earlier TrialMOSAIC - Same Disease

Citation

Bretthauer M, Løberg M, Wieszczy P, et al. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. N Engl J Med. 2022;387(17):1547-1556. doi:10.1056/NEJMoa2208375

In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening.