Objective Colorectal cancer (CRC) screening programmes based on faecal immunochemical testing for haemoglobin (FIT) typically use a screening interval of 2 years. We aimed to estimate how alternative FIT strategies that use a lower than usual positivity threshold followed by a longer screening interval compare with conventional strategies.

Methods We analysed longitudinal data of 4523 Dutch individuals (50–74 years at baseline) participating in round I of a one-sample FIT screening programme, of which 3427 individuals also participated in round II after 1–3 years. The cohort was followed until 2 years after round II. In both rounds, a cut-off level of ≥50 ng haemoglobin (Hb)/mL buffer (corresponding to 10 µg Hb/g faeces) was used, representing the standard scenario. We determined the cumulative positivity rate (PR) and the numbers of subjects diagnosed with advanced adenomas (N_AdvAd) and early stage CRC (N_earlyCRC) in the cohort over two rounds of screening (standard scenario) and compared it with hypothetical single-round screening with use of a lower cut-off and omission of the second round (alternative scenario).

Results In the standard scenario, the cumulative (ie, round I and II combined) PR, N_AdvAd and N_earlyCRC were 13%, 180% and 26%, respectively. In alternative scenarios using a cut-off level of respectively ≥11 and ≥22 ng/HbmL buffer (corresponding to 2 and 4 µg Hb/g faeces), the PRs were 18% and 13%, the N_AdvAd were 180 and 162 and the N_earlyCRC ranged between 22–27 and 22–26.

Conclusions The diagnostic yield of FIT screening using a lowered positivity threshold in combination with an extended screening interval (up to 5 years) may be similar to conventional FIT strategies. This justifies and motivates further research steps in this direction.