Characterizing the epidemiology and natural history of colorectal cancer using fecal immunochemical test data from screening programs: a modelling study

Colorectal cancer (CRC) epidemiology remains insufficiently characterized in many settings, limiting optimal prevention strategies. Using quantitative fecal immunochemical test (FIT) data from 248,692 first-time participants (aged 49–77; 56% female) in the Hong Kong CRC Screening Programme, we developed a natural history model incorporating adenoma and serrated pathways with stage-specific FIT distributions. Colonoscopy referral was triggered if either of two submitted samples exceeded 100 ng/mL (13% positivity). We estimated that 37% (95% credible interval = 36–39%) of males and 27% (26–29%) of females had colorectal neoplasms at age 50; ~8% had advanced colorectal neoplasms (advanced adenoma, serrated lesions, or CRC). Prevalence of advanced neoplasms increased ~ 0.5% per year after age 50. Annual progression to CRC was ~ 4% for advanced adenoma and 1–2% for serrated lesions. Preclinical CRC advanced from stages I-II to III-IV within 3–4 years. At the 100 ng/mL threshold, FIT demonstrated 88–97% sensitivity for CRC. The positive predictive value for advanced neoplasms rose from ~ 20% at age 50 by ~ 1% annually, while the negative predictive value remained > 90%. Males with advanced neoplasms had higher FIT values than females. Quantitative FIT data thus enables robust characterization of CRC epidemiology and progression, providing a foundation for evaluating screening strategies and cost-effectiveness.