We aim to improve the yield and effectiveness of the Dutch colorectal cancer screening program by using a personalized screening strategy based on fecal Hemoglobin concentration in previous screening round for participants with a negative fecal immunochemical test (FIT).

A fecal Hemoglobin concentration just below the cut-off of the fecal immunochemical test (FIT) is associated with a higher risk for the detection of colorectal cancer of advanced adenomas at consecutive screenings. Individuals with these higher fecal Hemoglobin concentrations may benefit from shorter screenings interval, whereas individuals without any fecal Hemoglobin concentrations could benefit from longer screening intervals.

A randomized controlled trial will be conducted within the national CRC screening program among individuals with a negative FIT in the previous screening round. Individuals in the intervention arm will receive an invitation after 1, 2, or 3 years depending on their fecal Hemoglobin concentration in the previous round, whereas individuals in the control arm will receive an invitation after 2 years according to current practice.

The overall aim of this study is to improve the balance between harms and benefits of CRC screening, by using a personalized approach based on fecal Hemoglobin concentration at previous screening. More specifically, this study has three goals:

1. Evaluate the superiority of risk-based FIT screening in a randomized controlled study embedded in a running national screening program;
2. Evaluate the feasibility and acceptability of risk-based FIT screening in a national screening program;
3. Estimate the long-term effect of personalized screening versus uniform screening.

To achieve these goals a randomized controlled trial, focus groups and microsimulation modelling will be conducted.

Inclusion Criteria:

• Previous negative FIT (below the cut-off of 47 microgram per gram feces)

Exclusion Criteria:

• Previously tested with FIT cut-off of 15 microgram per gram feces

Outcomes of the study will be stored in the national screening information system, owned by a third-party sources. Data cannot be publicly shared.