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Individuals invited to undergo screening colonoscopy had a lower risk of colorectal cancer compared with those who did not undergo screening, a European randomized trial found, though the reduction was lower than researchers had expected.

In the Northern-European Initiative on Colorectal Cancer ( trial, an intention-to-screen analysis demonstrated that the risk of colorectal cancer at 10-year follow-up was 0.98% in the invited group compared with 1.20% in the usual-care (no screening) group (risk ratio [RR] 0.82, 95% CI 0.70-0.93), a relative 18% risk reduction, reported Michael Bretthauer, MD, PhD, of the University of Oslo in Norway, and colleagues.

They found that the number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI 270-1,429), according to the findings in the , which were also presented at United European Gastroenterology Week 2022.

No significant difference was seen for death from colorectal cancer, at 0.28% in the invited group and 0.31% in the usual-care group (RR 0.90, 95% CI 0.64-1.16), while the risk for death from any cause over the study period was nearly identical (11.03% and 11.04%, respectively).

"Although we observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer-related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned," wrote Bretthauer and colleagues.

The NordICC trial involved 84,585 healthy men and women (ages 55 to 64) drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. These participants were randomly assigned in a 1:2 ratio to either receive an invitation to undergo a single screening colonoscopy or to receive usual care.

"This relatively small reduction in the risk of colorectal cancer and the nonsignificant reduction in the risk of death are both surprising and disappointing," observed Jason A. Dominitz, MD, of the University of Washington School of Medicine in Seattle, and Douglas J. Robertson, MD, of the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, writing in an .

They are suggesting several potential explanations for these "discouraging results," including the fact that less than half of the participants (42%) actually underwent colonoscopy. "Screening can only be effective if it is performed," the editorialists pointed out.

In an adjusted per-protocol analysis, the researchers found that if all those who were randomly assigned to screening had actually undergone colonoscopy it would have reduced the incidence of colorectal cancer by 31% (RR 0.69, 95% CI 0.55-0.83) and the risk of colorectal cancer-related death by 50% (RR 0.50, 95% CI 0.27-0.77).

Another explanation for the results, Dominitz and Robertson surmised, could be that the benefits of colonoscopy "take time to be realized." Echoing that suggestion, the researchers pointed out that the benefits of endoscopic screening with respect to the risk of colorectal cancer should come earlier compared with those regarding the risk of colorectal cancer-related death.

"The lack of a significant screening benefit with respect to colorectal cancer-related death in intention-to-treat analyses should therefore be interpreted in this context," Bretthauer and co-authors wrote. "Optimism related to the effects of screening on colorectal cancer-related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses."

However, the authors also noted that while the 31% reduction in the risk of colorectal cancer demonstrated in the adjusted analysis "is a clinically relevant benefit," it is still lower than what is anticipated in clinical guidelines based on observational and modeling studies, and similar to the estimates observed in trials of sigmoidoscopy screening.

"Thus, these results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy," the team wrote. "Future analyses of our trial results may provide more precise estimates of the per-protocol effects of colonoscopy screening for comparison purposes with other screening tests."

If the results of the NordICC trial represent the real-world performance of population-based screening colonoscopy, it might be difficult to justify the risk and expense of this form of screening when "simpler, less-invasive strategies" are available, Dominitz and Robertson concluded. They noted that while the current results "may, in the near term, temper enthusiasm for screening colonoscopy, additional analyses, including longer follow-up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test."

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