Effectiveness of initiating FIT screening at age 45: Comparative yield with adults aged 50-54 years

Background and aim: Over the past two decades, the incidence of early-onset colorectal cancer (CRC) has risen in several high-income countries. To address this trend, the United States Preventative Services Task Force recommended lowering the starting age for CRC screening from 50 to 45 years based on estimates from microsimulation models. However, real-world evidence on the screening yield across diverse populations remains limited. Methods: A population-based CRC screening program has been implemented since 2020 in a region with high CRC incidence (Zhejiang Province, China). The program primarily targeted individuals aged ​50-74 years but ​also included those aged 40-49​ years. Screening consisted of two-sample fecal immunochemical testing (FIT), with colonoscopy offered to individuals testing positive on either sample. We compared screening outcomes between participants aged 45-49 years and 50-54 years, including: (1) FIT positivity (threshold of 20 μg hemoglobin per gram of feces); (2) colonoscopy completion; and (3) positive predictive values (PPV, cases detected among those with a positive FIT and available colonoscopy) for neoplasia. Advanced neoplasia included CRC, advanced adenoma and advanced serrated lesion. Variables with standardized mean differences greater than 0.1, including sex, fruit intake, and year of participation, were included in the propensity score model for 1:1 matching between age groups. Risk ratios (RRs) were estimated using a Poisson mixed-effects model. Results: After propensity score matching, 89 446 subjects aged 45-49 and 89446 subjects aged 50-54 who completed the FIT test were selected, with comparable baseline characteristics. The FIT positivity in the 45-49 age group was 10.61%, which was lower than 11.02% in the 50-54 age group (RR, 0.96; 95% CI, 0.94-0.99), with similar colonoscopy adherence (46.75% vs 47.43%; RR, 0.99; 95% CI, 0.95-1.03). Compared with the 50-54 age group, the 45-49 age group had significantly lower PPVs for any adenoma (15.82% vs 19.91%; RR, 0.79; 95% CI, 0.72-0.88) and advanced neoplasia (6.06% vs 8.25%; RR, 0.73; 95% CI, 0.63-0.86).In subgroup analyses of 45-49 age group, the PPVs for advanced neoplasia among participants with smoking, BMI ≥28 kg/m 2 , frequent alcohol drinking, personal history of adenoma or a family history of CRC exceeded that observed in the 50-54 age group. Conclusions: Individuals aged 45-49 years had comparable colonoscopy adherence to those aged 50-54 years but a lower yield for adenomas and advanced neoplasia. Higher yields among younger individuals with risk factors highlight the potential of risk-stratified approaches. These findings contribute population-specific evidence to inform ongoing discussions on optimal screening initiation age, but further longitudinal, cost-effectiveness, and programmatic evaluations are warranted.