Colorectal Cancer Screening at Younger Ages: A Multicutoff Analysis of FIT Performance

Due to rising early-onset colorectal cancer (CRC) incidence, lowering the starting age for CRC screening is considered in many countries. However, data on diagnostic performance of fecal immunochemical tests (FIT), the most commonly employed CRC screening test, in younger populations remain limited. This study assessed FIT diagnostic performance for detecting advanced neoplasia (AN) at various cutoffs of fecal hemoglobin (Hb) concentrations in individuals aged 55 years or younger.

A total of 1724 participants aged 55 years or younger who underwent screening colonoscopy were recruited in a cross-sectional study conducted in Germany. Fecal Hb concentrations were measured in all participants using FIT (Sentinel FOB Gold) prior to colonoscopy. AN prevalence was determined by screening colonoscopy. FIT performance was evaluated based on positivity rate, sensitivity, specificity, and predictive values at various Hb concentration thresholds.

AN was detected in 139 participants (8.1%), including 5 participants (0.3%) with CRC. At the manufacturer-recommended cut off of 17 µg Hb/g stool, positivity rate was 7.7%, yielding a sensitivity of 26.6% (95% confidence interval [CI], 20.0-34.5), specificity of 94.0% (95% CI, 92.7-95.1), positive predictive value (PPV) of 28.0% (95% CI, 21.1-36.2), and negative predictive value (NPV) of 93.6% (95% CI, 92.3-94.7) for AN detection. These measures strongly varied across the range of cutoffs employed in FIT-based screening programs. Men showed higher AN prevalence, positivity rate, sensitivity, and PPV across the investigated Hb range, whereas sex differences in specificity and NPV were minimal.

Our study provides detailed quantitative information on diagnostic performance characteristics of FIT in a younger CRC screening population, which may inform and optimize effectiveness and cost-efficiency of CRC screening at younger ages.