Predicting prostate cancer progression: protocol for a retrospective cohort study to identify prognostic factors for prostate cancer outcomes using routine primary care data.

INTRODUCTION: Prostate cancer is the most common cancer in men in the UK, with nearly 40 000 diagnosed in 2014; and it is the second most common cause of male cancer-related mortality. The clinical conundrum is that most men live with prostate cancer rather than die from it, while existing treatments have significant associated morbidity. Recent studies have shown very low mortality rates (1% after a median of 10-year follow-up) and no treatment-related reductions in mortality, in men with localised prostate cancer. This study will identify prognostic factors associated with prostate cancer progression to help differentiate aggressive from more indolent tumours in men with localised disease at diagnosis, and so inform the decision to adopt conservative (active surveillance) or radical (surgery or radiotherapy) management strategies.

METHODS AND ANALYSIS: The Clinical Practice Research Datalink (CPRD) contains 57 318 men who were diagnosed with prostate cancer between 1 January 1987 and 31 December 2016. These men will be linked to the Office for National Statistics (ONS) and the National Cancer Registration and Analysis Service registry databases for mortality, TNM stage, Gleason grade and treatment data. Men with a diagnosis date prior to 1 January 1987 and men with lymph node or distant metastases at diagnosis will be excluded. A priori determined prognostic factors potentially associated with prostate cancer mortality, the end point of cancer progression, will be measured at baseline, and the participants followed through to development of cancer progression, death or the end of the follow-up period (31 December 2016). Cox proportional hazards regression will be used to estimate crude and mutually adjusted HRs. Mortality risk will be predicted using flexible parametric survival models that can accurately fit the shape of the hazard function.

ETHICS AND DISSEMINATION: This study protocol has approval from the Independent Scientific Advisory Committee for the UK Medicines and Healthcare products Regulatory Agency Database Research (protocol 17_041). The findings will be presented in peer-reviewed journals and local CPRD researcher meetings.