European trial finds reduction in cancers but not deaths with invitation to colonoscopy screening

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, a randomized trial found.

Researchers performed a pragmatic, randomized trial involving healthy men and women ages 55 to 64 years from population registries in Poland, Norway, and Sweden from 2009 to 2014. Participants in the Nordic-European Initiative on Colorectal Cancer trial were randomized in a 1:2 ratio to receive an invitation to undergo a single screening colonoscopy (invited group) or to receive no invitation or screening (usual care group). Primary end points were rates of colorectal cancer and related death, and the secondary end point was all-cause mortality. Results were published Oct. 9 by the New England Journal of Medicine.

Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden, 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual care group. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group versus 622 cases in the usual care group.

In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual care group, a risk reduction of 18% (risk ratio [RR], 0.82; 95% CI, 0.70 to 0.93). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1,429). However, the risk of death from colorectal cancer was not significantly different, at 0.28% in the invited group and 0.31% in the usual care group (RR, 0.90; 95% CI, 0.64 to 1.16). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual care group (RR, 0.99; 95% CI, 0.96 to 1.04).

“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,” the study authors observed. They noted that when they adjusted the analysis to estimate the effects if all invited patients had undergone screening, the risk of colorectal cancer decreased from 1.22% to 0.84% and the risk of colorectal cancer-related death decreased from 0.30% to 0.15%. The authors also noted that longer follow-up may be needed to capture the full effects of screening.

“This relatively small reduction in the risk of colorectal cancer and the nonsignificant reduction in the risk of death are both surprising and disappointing; these findings raise the question of why previous studies would have shown greater effectiveness of sigmoidoscopy than colonoscopy,” an accompanying editorial noted.

The editorial highlighted the finding that only 42% of invited participants underwent colonoscopy, compared to 58% to 87% in sigmoidoscopy trials, and that the authors had previously reported that 29% of the trial endoscopists had an adenoma detection rate below the recommended minimum threshold of 25%. The effects of invitations to colonoscopy in countries where screening is not well established may be very different than in the U.S., where it is broadly recommended, the editorial said.

“If the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and [fecal immunochemical test]) are available,” it concluded. “However, with increased levels of participation in screening and with high-quality examinations, greater reductions in the incidence of colorectal cancer and related death would be expected.”