Abstract: The Flemish population-based colorectal cancer (CRC) screening programme, initiated in October 2013, offers a free biennial faecal immunochemical test (FIT) to eligible individuals aged 50-74 years. This PhD research aimed to 1) Assess the programme’s impact on CRC incidence, mortality, and survival; 2) Investigate suboptimal response rates by exploring screening with outside tests, reasons for inconsistent participation, and population preferences for CRC screening; 3) Identify FIT interval cancer characteristics and explore strategies to optimize FIT cut-off and screening interval to reduce FIT interval cancers. Results indicate that the programme has effectively reduced CRC incidence, mortality and improved survival, with a more pronounced impact in men. Screening with outside tests has limited impact on response rates inside the programme but presents challenges such as cost, inadequate result registration and follow-up, and insufficient quality control. Encouraging a shift to organised screening is important. Persistent challenges to increasing uptake include language barriers for individuals with a migrant background, postponed screening due to time constraints and competing priorities, and the misconception that CRC screening is only necessary when symptoms are present. GPs play a vital role in promoting CRC screening and addressing barriers and misconceptions among their patients. Factors associated with a higher risk of having FIT interval cancer versus a screen-detected CRC include female gender, older age, right side and rectum locations, advanced stage, and high grade. The chosen FIT cut-off and screening interval in Flanders are considered optimal with regard to FIT interval cancer, as lowering FIT cut-off or shortening screening interval would have minimal impact on the occurrence of FIT interval cancers. The current evidence does not support expanding the CRC screening programme by reducing the starting age for screening, lowering the FIT cut-off, or shortening the screening interval. ...