Prediction of Prostate Cancer Risk to Improve PSA Screening: A Statistical Modeling Approach
Project Leader: Mark Clements
PhD Student: Thorgerdur Palsdottir
Aims: Develop methods and tools to predict and simulate prostate cancer incidence and mortality, and apply those tools to reduce the harms from prostate cancer testing in the Nordic countries. Background: Prostate cancer is the most common cancer diagnosis and the second most common cause of cancer death in the Nordic countries, constituting 32% of male cancer diagnoses and 18% of male cancer deaths in 2009. Accounting for 40% of prevalent male cancers in the region, the health burden and costs on the health care system are substantial. Prostate cancer mortality rates are very high in the Nordic countries and this pattern is unlikely to be explained by poor health care. Mortality rates have begun to decline in the last 5-10 years, which may be due to improvements in care and/or the introduction of prostate-specific antigen (PSA) testing. PSA test uptake is now high in some Nordic populations, where in Stockholm 50-75% of men aged 50 years and over have had a PSA test (Nordström et al., 2013).
There is uncertainty in how best to use the PSA test. In many men it may extend life through early detection and radical treatment, while it may also lead to over-diagnosis. There is also uncertainty about the appropriate management of prostate cancer as radical treatment has common side effects. Recent analyses of costs and effectiveness of PSA screening for prostate cancer suggest that current PSA screening is not effective, where the harms outweigh any mortality benefits from early detection, although conclusions are sensitive to the choice of health utilities (Chilcott, Hummel, & Mildred, 2010; Pataky et al., 2014). There is increasing evidence that combining biomarkers can improve the prediction of prostate cancer (Landers et al., 2005). The research question is whether improved biomarkers and organised prostate cancer screening can reduce the harms from screening and maintain any mortality benefit in the Nordic countries.
To address this research question from an epidemiological perspective, the Cancer Risk Prediction (CRisP) Center in Stockholm is undertaking the STHLM3 diagnostic trial during 2013-2014. The STHLM3 study uses a paired design, where men who have a PSA above 1 ng/ml undertake a panel of biomarkers; if their PSA exceeds 3 ng/ml or their biomarker panel prediction exceeds a threshold c, then those men are referred to biopsy to determine their cancer status. Men not referred to biopsy will then be randomised to one of two re-screening protocols. The aim of the study is to maintain comparable sensitivity for advanced prostate cancer, while improving specificity, leading to fewer men being referred to biopsy. CRisP has also linked all PSA and prostate biopsies in Stockholm to the population and health registers for the period 2003-2012, which allows for a detailed description of prostate cancer testing in a Nordic city.
To address the research question from an eScience perspective, we aim to improve the tools used for prediction of prostate cancer and develop tools for microsimulation of prostate cancer testing, incidence, mortality and effectiveness in the Nordic countries. In particular, we want to predict the effectiveness of different screening scenarios without performing separate randomised controlled trials, where we want to evaluate the effectiveness of the scenarios using in silico simulations.