A dynamic prediction model for early detection of colorectal cancer using routine blood test results from primary care

Conference:

SAPC ASM 2021 - virtual

Talk Code:

4B.5

Presenter:

Pradeep S. Virdee

Twitter:

@PradeepVirdee

Co-authors:

Pradeep S. Virdee, Jacqueline Birks, Tim Holt

Author institutions:

Centre for Statistics in Medicine (NDORMS, University of Oxford, Oxford, UK), Nuffield Department of Primary Care Health Sciences (University of Oxford, Oxford, UK)

Problem

Colorectal cancer is the fourth most common type of cancer in the UK. It develops gradually in the bowel lining. Around 55% of patients are diagnosed at a late stage (Stage 3 and 4), where likelihood of survival is reduced: five-year survival is 93% at Stage 1 versus 10% at stage 4. This highlights the importance of early detection. The full blood count (FBC) is a common blood test in primary care. Some FBC indices, including haemoglobin, mean cell volume, and platelet count, are known to change over time as the cancer develops. We built a dynamic prediction model that uses repeated FBC measurements of these three indices to identify risk of a colorectal cancer diagnosis two years in the future.

Approach

We performed a cohort study using FBC data from the Clinical Practice Research Datalink linked with colorectal cancer diagnoses from the National Cancer Registration and Analysis Service. We developed a multivariate joint model of longitudinal and time-to-event data for males and females separately. Using historical repeated FBCs over five years prior to baseline (last included FBC), age-adjusted trajectories in haemoglobin, mean cell volume, and platelet measurements informed two-year risk of colorectal cancer diagnosis, using a Cox model. Model performance was assessed using Harrell’s c-statistic for discrimination.

Findings

Due to the computational challenges of developing joint models, we used a random sample of 150,000 males and 150,000 females, of whom 0.4% (n=591) and 0.3% (n=438) were diagnosed with colorectal cancer two years after their baseline FBC, respectively. Simultaneous age-adjusted decreases in haemoglobin and mean cell volume and increase in platelets from the population trajectory (patients with no diagnosis recorded) increased the risk of diagnosis for both males and females (each p<0.05). The c-statistic was 0.749 (95% CI: 0.729, 0.768) for males and 0.736 (95% CI: 0.713, 0.759) for females.

Consequences

Our dynamic prediction model has the potential to utilise small changes in FBC indices occurring simultaneously over time to identify patients who need further investigation for colorectal cancer. Such changes can appear before overt symptoms occur, so the prediction model could facilitate earlier detection. Further model performance statistics will be presented, including plots of observed versus predicted probabilities for calibration.

Submitted by:

Pradeep Virdee

Funding acknowledgement:

Pradeep S. Virdee is funded by the National Institute for Health Research (NIHR), Doctoral Research Fellowship programme (DRF-2018-11-ST2-057) for this research project. Jacqueline Birks is funded by the NIHR Oxford Biomedical Research Centre (BRC), Oxford University Hospitals NHS Foundation Trust. This report presents independent research and the views expressed are those of the authors and not necessarily those of the funders, NHS, or Department of Health and Social Care.