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.