Advancing the Evaluation of Risk-Stratified Colorectal Cancer Screening by Simulating Quantitative Fecal Hemoglobin...

Background. Growing evidence indicates that fecal hemoglobin (f-Hb) concentrations from prior negative fecal immunochemical tests (FITs) can predict the future detection of colorectal cancer (CRC) and advanced neoplasia. As a result, there are opportunities for risk-based screening tailored to prior FIT outcomes. However, current CRC screening decision models do not explicitly simulate quantitative f-Hb concentrations. They simulate only a binary positive or negative test result based on the sensitivity and specificity of the underlying lesions, which makes it impossible to evaluate risk-based screening by f-Hb with these models. Methods. We extended our well-established MISCAN-Colon microsimulation model with a module that simulates quantitative f-Hb concentrations based on age, sex, and the presence of colorectal lesions. This module was based on a zero-inflated negative binomial mixed-effect model and calibrated and validated using observational data from the Dutch national CRC screening program between 2014 and 2020. The new MISCAN-Colon was then applied to a case study, in which we compared the effectiveness of uniform biennial screening intervals versus risk-based intervals (3 y after a FIT result of 0 µg/g, 2 y after >0-15 µg/g, and 1 y after >15-46.9 µg/g). Results. The updated model closely reflected real-world results, including positivity rate (observed: 4.7%, model: 4.3%), CRC detection rates (observed: 0.3%, model: 0.4%), f-Hb distributions, and longitudinal patterns across 3 screening rounds. Compared with biennial screening, the risk-based strategy resulted in slightly more CRC cases (+5%) and deaths (+11%) but required substantially fewer FITs (-28%) and colonoscopies (-13%). Conclusions. Integrating the f-Hb module into MISCAN-Colon enables explicit modeling of f-Hb concentrations and facilitates the evaluation of risk-based screening by prior f-Hb concentrations.

In colorectal cancer screening (CRC), risk-based screening using fecal hemoglobin (f-Hb) from prior screening rounds has been suggested to improve the balance between the benefits and harms of screening. However, the added value of this approach has never been quantified because none of the existing decision models for CRC screening simulate f-Hb concentrations.We used data from the Dutch national CRC screening program to extend the widely used MISCAN-Colon microsimulation model to explicitly simulate an individual's f-Hb concentration based on sex, age, and the presence of colorectal lesions.This model accurately reproduced cross-sectional and longitudinal associations between f-Hb concentration and screen-detected colorectal lesions, and model estimates showed that risk-based screening using f-Hb concentrations could be more efficient than current uniform screening.