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.

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death.

Aim: 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.

Methods: 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.

Results: At a CRC risk threshold of 0.6% (equivalent to f-Hb = 10 μg Hb/g (μg/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 μg/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 μg/g.

Conclusions: 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 μg/g.