Introduction: The emergence of blood-based biomarkers intensifies the demand for data on the real-world long-term uptake and yield of FIT.

Objectives: To characterize long-term participation patterns, FIT positivity rates and yields for neoplasia in the Catalan FIT-based CRC screening program since 2010.

Methods: Participation, FIT positivity and yield (CRC; high-risk precursors = advanced adenoma/sessile serrated lesion or 5+ non-advanced ones) were determined with 2 perspectives: 1) Program (all persons regardless of age at entry); 2) Adherent cohort (entry at 50-51 yo with longitudinal consistent/frequent [100%/66-99% of rounds offered] participation).

Results: Participation patterns: Among 2.81M persons with 1-9 rounds offered/person, participation patterns were: 29.2% consistent, 8.6% frequent, 16.0% occasional [1-65%], and 46.2% never. FIT participation & positivity: Per-round FIT completed/offered ranged 39-60% for the Program, and 91-98% for the Adherent Cohort. FIT-positivity was highest in round 1 and settled at a steady state in rounds 2+ in both scenarios. Neoplasia yield: CRC/1,000 persons completing FIT was substantially higher in round 1 vs. rounds 2+ in both scenarios. Similarly, high-risk precursor and CRC detection were highest in round 1, with CRC detection settling at a steady state and high-risk precursor detection remaining substantial in rounds 2+. Adherent Cohort vs. Program: FIT-positivity and neoplasia yield were higher at a given round in the Program vs. Adherent cohort.

Conclusions: With current program design, 46% of eligible persons do not participate, and among participants, 70% are consistent/frequent. Yield is highest at round 1, as expected due to detection of prevalent neoplasia, but yield at rounds 2+ remains substantial. The Program vs. Adherent cohort results across rounds with similar ages suggest that consistent/frequent participation may decrease CRC incidence, presumably by removal of CRC precursors.