Analysis Challenges NordICC Trial Conclusions on CRC Screening and Mortality
A re-evaluation of the Northern European Initiative on Colorectal Cancer (NordICC) trial suggests that the conclusion—that screening colonoscopy reduces colorectal cancer (CRC) incidence but not mortality—rests on insufficient follow-up.
The original trial randomized more than 84,000 average-risk adults aged 55–64 years across 4 European countries to receive an invitation to colonoscopy or usual care, with results reported at 10 years. The intention-to-screen analysis demonstrated a modest reduction in CRC incidence (relative risk [RR] 0.82) but no statistically significant effect on CRC-related or all-cause mortality.
The new analysis emphasizes that mortality outcomes in screening trials require substantially longer follow-up—often 15 to 20 years—to mature, given the natural history of colorectal cancer and lag between incidence reduction and death. The investigators, writing in Alimentary Pharmacology and Therapeutics, noted that evidence from sigmoidoscopy trials and other screening modalities demonstrates that mortality curves separate meaningfully only after extended observation. Thus, the absence of mortality benefit at 10 years in NordICC likely reflects premature reporting rather than true lack of effect, the authors stated.
Adherence rates further complicate interpretation. Only 42% of participants randomized to the invitation arm underwent colonoscopy, diluting observed effects in intention-to-screen analysis. Per-protocol and instrumental variable analyses suggested substantially greater reductions in both incidence and CRC-related mortality among those actually screened. While such analyses are susceptible to confounding, they reinforce the biologic plausibility that incidence reduction will translate into mortality benefit once sufficient time has elapsed.
The investigators also highlight the danger of miscommunicating trial results to clinicians and the public. Headlines suggesting colonoscopy fails to reduce the risk of death may undermine confidence in an established preventive strategy, despite clear evidence of adenoma detection and removal reducing progression to invasive cancer.
Reference
Brenner H, Sergeev D, Heisser T, Hoffmeister M. Effects of screening colonoscopy on colorectal cancer mortality: lessons from comparative analyses of randomised trials. Aliment Pharmacol Ther. Published online June 10, 2025. doi:10.1111/apt.70231
