COLONPREV Trial: FIT vs Colonoscopy for Colorectal Cancer Screening

Background and Context

Colorectal cancer is Europe’s second leading cause of cancer death, accounting for about 150,000 deaths each year. Five-year survival exceeds 90% when the disease is detected at stage I but falls below 15% at stage IV, so timely detection through regular screening is critical. Lifestyle measures—physical activity, a fiber-rich diet, limited processed meat, moderate alcohol consumption, and avoiding tobacco—further lower risk and complement, but do not replace, organized screening.

Study Design and Methodology

The COLONPREV pragmatic randomized controlled trial enrolled 57,404 average-risk adults aged 50 to 69 and compared a single screening colonoscopy with biennial fecal immunochemical testing (FIT). COLONPREV was a randomized controlled non-inferiority trial, a design that balances both measured and unmeasured confounders through random allocation. The study was conducted in Spain, and its primary results were published in The Lancet after peer review. Participants were randomized at a 1:1 ratio: one group received an invitation to a single colonoscopy, reflecting the test’s approximate ten-year protective window; the other group received invitations to FIT every two years, matching the possibility that lesions can start bleeding at any point.

Key Results and Effectiveness

After 10 years, the risk of colorectal cancer death was 0.22% in those offered colonoscopy and 0.24% in those offered FIT. The absolute difference of –0.02 percentage points was within the prespecified non-inferiority margin, and the p-value for non-inferiority was 0.0005, indicating that FIT is not materially less effective at preventing death. International benchmarks require either a 30% mortality reduction or statistical non-inferiority to colonoscopy. FIT meets this requirement and can therefore serve as an effective alternative. Because effectiveness is comparable, practical considerations become the next deciding factor.

How Each Test Works

FIT detects hidden blood by using antibodies specific to human hemoglobin. A positive result indicates bleeding from a polyp or tumor somewhere in the large bowel. The test requires no dietary restrictions or bowel preparation. Individuals collect a small stool sample with a supplied wand, seal it in a buffered tube, and mail it to the laboratory.

Colonoscopy is considered the reference test because it visualizes the entire mucosa, permits biopsy, and allows immediate removal of precancerous polyps.

Practical Differences: Convenience, Cost, and Risks

FIT requires a small stool sample collected at home and mailed to a laboratory. Colonoscopy, in contrast, involves bowel cleansing, intravenous sedation, and insertion of a flexible endoscope through the entire colon, with associated risks of bleeding and perforation. Collecting a FIT sample takes minutes, whereas colonoscopy typically occupies an entire day, including recovery time and the need for an escort due to sedation. Cost analyses from European screening programs show that a FIT kit and processing together cost roughly €10, while colonoscopy generally costs several hundred euros in public systems and more than €1,000 in private settings. These differences make FIT easier to deploy at scale and less burdensome for both patients and healthcare budgets.

Participation Rates and Population Impact

In COLONPREV, 39.9% of invitees completed a FIT and 31.8% underwent colonoscopy. Participation was defined as returning the stool kit or attending the endoscopy within the recommended window. The higher uptake with FIT increases the proportion of the population that receives any screening at all, which can lead to more early detections even when individual-level effectiveness is the same.