Development and validation of a novel algorithm to estimate risk of developing prostate cancer in asymptomatic men: a cohort study

Hippisley-Cox, Julia; Coupland, Carol

Abstract

Abstract Objective: To develop and validate a risk prediction equation to predict absolute risk of prostate cancer in asymptomatic men with prostate specific antigen (PSA) tests in primary care. Design: Open cohort study. Setting: Routine data from 1098 QResearch® English general practices linked to mortality, hospital and cancer records for model development. Two separate sets of practices for validation. Participants 844,455 men aged 25-84 years with prostate specific antigen (PSA) tests recorded and free of prostate cancer at baseline in the derivation cohort; 292,084 and 316,583 in each validation cohort. Exposures Risk factors assessed at baseline: PSA, age, ethnicity, deprivation, BMI, smoking, family history of prostate cancer, diabetes, mental illness. Main outcomes: Primary outcome was incident prostate cancer. Secondary outcomes were prostate cancer mortality and high-grade cancer. Cox proportional hazards models used to derive 10-year risk equations. Measures of performance were determined in both validation cohorts. Results: 40,821 incident cases of prostate cancer in the derivation cohort. The risk equation included PSA level, age, deprivation, ethnicity, smoking, family history of prostate cancer, serious mental illness, diabetes and BMI. The risk equation explained 70.4% (95%CI 69.2 to 71.6) of the variation in time to diagnosis of prostate cancer (R2); D statistic = 3.15 (95%CI 3.06 to 3.25); Harrell’s C = 0.917 (95%CI 0.915 to 0.919). Conclusion and relevance: The equation provides valid measures of absolute risk and had higher sensitivity both for incident prostate cancer, high grade cancers and prostate cancer mortality, than a simple approach based on age and PSA threshold.

• Journal Article Type: Article
• Acceptance Date: Sep 8, 2020
• Online Publication Date: Dec 9, 2020
• Publication Date: 2021-05
• Deposit Date: Nov 18, 2020
• Publicly Available Date: Dec 10, 2021
• Journal: British Journal of General Practice
• Print ISSN: 0960-1643
• Electronic ISSN: 1478-5242
• Publisher: Royal College of General Practitioners
• Peer Reviewed: Peer Reviewed
• Volume: 71
• Issue: 706
• Pages: E364-E371
• DOI: https://doi.org/10.3399/bjgp20X714137
• Public URL: https://nottingham-repository.worktribe.com/output/5052492
• Publisher URL: https://bjgp.org/content/early/2020/12/09/bjgp20X714137?versioned=true
• Additional Information: This is an early version of Predicting The Risk Of Prostate Cancer In Asymptomatic Men: A Cohort Study To Develop And Validate A Novel Algorithm, available here: https://nottingham-repository.worktribe.com/output/5509991