Colon to Rectum
Lancet. 2025;405(10486):1231-1239
Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): A pragmatic, randomised, controlled, non-inferiority trial
Background: Colonoscopy and the faecal immunochemical test are accepted strategies for colorectal cancer screening in the average-risk population (i.e., people aged ≥ 50 years without personal or family history of colorectal cancer). The aim of this trial was to compare whether invitation to screening with faecal immunochemical test was non-inferior to colonoscopy in a screening programme.
Methods: COLONPREV was a pragmatic, randomised, controlled, non-inferiority trial done at 15 tertiary hospitals across 8 regions of Spain. Eligible participants were presumptively healthy and aged between 50 years and 69 years without a personal history of colorectal cancer, adenoma or inflammatory bowel disease, family history of hereditary or familial colorectal cancer (i.e., 2 or more first-degree relatives with colorectal cancer or 1 diagnosed before age 60 years), severe comorbidities, or previous colectomy. Participants were randomly assigned (1:1) to one-time colonoscopy or biennial faecal immunochemical test before invitation to screening. The primary endpoint was colorectal cancer mortality at 10 years, assessed in the intention-to-screen population. An absolute difference of less than 0.16 percentage points was required to show non-inferiority.
Findings: Between June 1, 2009, and December 31, 2021, 57,404 individuals were randomly assigned to receive an invitation for colonoscopy (n = 28,708) or the faecal immunochemical test (n = 28,696). The intention-to-screen population consisted of 26,332 individuals in the colonoscopy group and 26,719 in the faecal immunochemical test group. In the intention-to-screen population, participation in any form of screening was 31.8% in the colonoscopy group and 39.9% in the faecal immunochemical test group (risk ratio [RR] = 0.79 [95% confidence interval [CI]: 0.77–0.82]). Faecal immunochemical testing was non-inferior to colonoscopy with regard to the risk of colorectal cancer mortality at 10 years: the risk was 0.22% (55 deaths) in the colonoscopy group and 0.24% (60 deaths) in the faecal immunochemical test group (risk difference -0.02 [95% CI: -0.10 to 0.06]; RR = 0.92 [95% CI: 0.64–1.32]; p[non-inferiority] = 0.0005).
Interpretation: Participation in screening was higher among individuals invited to faecal immunochemical test screening than colonoscopy screening. On the basis of participation observed in this study, a faecal immunochemical test-based programme was non-inferior to a colonoscopy-based programme for colorectal cancer-related mortality.
DOI: 10.1016/s0140-6736(25)00145-x
PD Dr. Armin Küllmer
PD Dr. Armin Küllmer, Head of Endoscopy, University Medical Center Freiburg, Department of Internal Medicine II, Hugstetter Str. 55, 79106 Freiburg, Germany
The COLONPREV study: Comparative evaluation of colorectal cancer screening strategies
Official colorectal cancer screening programs have been shown to be superior to opportunistic, ad hoc screening. The NordICC trial (DOI: 10.1056/nejmoa2208375) demonstrated that colonoscopy-based screening significantly reduces both the incidence and mortality of colorectal cancer. In parallel, many international screening strategies rely on repeated screening using fecal immunochemical tests (FIT).
The COLONPREV study is the first direct comparison of these 2 primary strategies for the early detection of colorectal cancer: a one-time colonoscopy versus repeated FIT screening in the typical risk population. With almost 50,000 patients and a follow-up period of 10 years, the scale of the study is evident. The results have direct implications for clinical practice and health policy debates. In this study, the FIT-based screening program achieved a significantly higher participation rate and was not inferior to colonoscopy in reducing colorectal cancer mortality after 10 years. These results suggest that repeated, low-threshold FIT screening is not only more practical, but also at least as effective as colonoscopy. A cost-effectiveness analysis of the study results is currently pending and is unlikely to reveal any cost disadvantages of the FIT strategy. On the other hand, colonoscopy was more effective, although not (yet) statistically significant.
It therefore remains to be seen how the results of the study will be interpreted and implemented in the different countries. Presumably, the countries that have so far relied on colonoscopy will retain it and vice versa for the FIT countries. There are arguments for both strategies. However, in countries that are considering the introduction of screening programs, COLONPREV provides a scientifically sound basis and makes a clear case for FIT as an effective, population-based strategy.
Importantly, both the NordICC and COLONPREV trials underscore a shared critical challenge: increasing public awareness and participation in colorectal cancer screening.