Full Blood Count Trends for Colorectal Cancer Detection in Primary Care: Development and Validation of a Dynamic Prediction Model

SIMPLE SUMMARY: Colorectal cancer is the fourth most common cancer and second most common cause of cancer-death in the UK. If diagnosed and treated early-stage, when the cancer has not spread, 9 in 10 patients are alive five years later. If diagnosed at a late-stage, when the cancer has spread, this drops to 1 in 10 alive. Early detection can save lives, but more than half of colorectal cancers are diagnosed late-stage in the UK. Growing tumours often cause subtle changes in blood test results that could help with earlier detection. For example, patients diagnosed with colorectal cancer often have an increasingly lowering haemoglobin for a few years before their diagnosis, which is not seen in patients without colorectal cancer. These differences as subtle so may be difficult for doctors in primary care to spot from a series of blood tests. We developed a computer-based tool to do this. This tool checks the changes in a patient’s blood test results over the last five years to see how likely they are to have colorectal cancer. We report this tool here and describe how well it works in identifying colorectal cancer cases using blood tests performed in primary care. ABSTRACT: Colorectal cancer has low survival rates when late-stage, so earlier detection is important. The full blood count (FBC) is a common blood test performed in primary care. Relevant trends in repeated FBCs are related to colorectal cancer presence. We developed and internally validated dynamic prediction models utilising trends for early detection. We performed a cohort study. Sex-stratified multivariate joint models included age at baseline (most recent FBC) and simultaneous trends over historical haemoglobin, mean corpuscular volume (MCV), and platelet measurements up to baseline FBC for two-year risk of diagnosis. Performance measures included the c-statistic and calibration slope. We analysed 250,716 males and 246,695 females in the development cohort and 312,444 males and 462,900 females in the validation cohort, with 0.4% of males and 0.3% of females diagnosed two years after baseline FBC. Compared to average population trends, patient-level declines in haemoglobin and MCV and rise in platelets up to baseline FBC increased risk of diagnosis in two years. C-statistic: 0.751 (males) and 0.763 (females). Calibration slope: 1.06 (males) and 1.05 (females). Our models perform well, with low miscalibration. Utilising trends could bring forward diagnoses to earlier stages and improve survival rates. External validation is now required.