COLOFIT: Development and internal-external validation of models using age, sex, faecal immunochemical and blood tests to optimise diagnosis of colorectal cancer in symptomatic patients

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death. Aim(s): To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations. Method(s): We included all adults (>= 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT. Predicted 1-year CRC diagnosis were calculated, and externally validated, using Cox proportional hazards modelling with selected multiple fractional polynomial transformations for age, faecal haemoglobin concentration (f-Hb) value, mean corpuscular volume (MCV), platelet count and sex. Result(s): At a CRC risk threshold of 0.6% (equivalent to f-Hb = 10 mug Hb/g (mug/g)) overall performance of the validated model across age strata using Harrell's C index was >= 0.91% (overall C-statistic 93%, 95% CI 92%-95%) with acceptable calibration. Using this model yields similar numbers of detected and missed cancers, but requires ~20% fewer investigations than a f-Hb >= 10 mug/g strategy. For approximately 100,000 people per year with symptoms of suspected CRC, we predict it might save > 4500 colonoscopies with no evidence that more cancers would be missed if we used our model compared to using FIT f-Hb >= 10 mug/g. Conclusion(s): Including age, sex, MCV, platelets and f-Hb in a survival analysis model to predict the risk of CRC yields greater diagnostic utility than a simple binary cut off f-Hb >= 10 mug/g.Copyright © 2025 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.