Prostate cancer is the most diagnosed cancer in men, with cardiovascular disease the leading cause of death among those with prostate cancer. Prostate cancer growth is commonly driven by male sex hormones which are called androgens, the most important being testosterone. Therefore, the standard treatment options for prostate cancer include medications that work to lower androgen levels. Gonadotrophin releasing hormone (GnRH) agonist and GnRH antagonist medications work, through different mechanisms, to reduce androgen levels.
Previous clinical trials and non-trial studies have produced mixed results but suggest the occurrence of cardiovascular complications (such as heart attacks and stroke) among men with prostate cancer may be higher in those treated with a GnRH agonist than a GnRH antagonist.
We will use anonymous data from GP and hospital records to ascertain trends in cardiac and cancer biomarkers and cardiovascular risk scores before and after GnRH agonist or GnRH antagonist treatment in men with diagnosed prostate cancer. Additionally, we will estimate the incidence of cardiovascular complications by treatment type (GnRH agonist or GnRH antagonist).
Our analysis will help understand the cardiovascular profile of men with prostate cancer who are treated with GnRH agonists or GnRH antagonists.
GnRH agonists and GnRH antagonists are standard treatment options for locally advanced and metastatic prostate cancer. Previous clinical trials and observational studies suggest GnRH agonists may lead to a higher incidence of cardiovascular complications than GnRH antagonists.
The aim of this descriptive retrospective cohort study is to investigate how underlying cardiovascular risk influences prostate cancer treatment and prognosis. Using CPRD Aurum and HES linked data, among men aged ≥40 years with a prostate cancer diagnosis we will identify two cohorts: 1) those treated with a GnRH agonist and 2) those treated with a GnRH antagonist.
Using a 12-month pre-treatment initiation period we will identify differences in values for a range of cardiac or cancer biomarkers of interest before treatment to values for each biomarker after treatment initiation. We will calculate cardiovascular risk scores using the QRISK3 algorithm, comparing changes in individual scores pre- and post-GnRH agonist or GnRH antagonist treatment initiation. Finally, we will identify major adverse cardiovascular event (MACE) outcomes, defined as myocardial infarction (MI), stroke and cardiovascular death which occur after GnRH agonist or GnRH antagonist treatment initiation and calculate the incidence of MACE per person-years stratified by cardiovascular risk level. Cardiovascular risk level will be categorised as established cardiovascular disease (CVD), QRISK3 score <10% & QRISK3 ≥10%.
Objective 1: we will describe the baseline demographic and clinical characteristics (see “Exposures, outcomes and covariates” section for more details)
Objective 2 & 3: GnRH agonist and GnRH antagonist treatment identified in CPRD Aurum data (see codelists in appendix)
Objective 4: Cardiac biomarkers of interest: (a) total, (b) high-density lipoprotein (HDL) and (c) low-density lipoprotein (LDL) cholesterol, (d) D-dimer level, (e) N-terminal proB-type natriuretic peptide (NT-proBNP), (f) C-reactive protein (CRP), (g) high-sensitivity troponin (hsTn) and (h) triglycerides. Cancer-related biomarkers of interest: (a) testosterone level, (b) prostate specific antigen (PSA), (c) white cell count (WCC), (d) platelet count, (e) TNM score and (f) Gleason score. All biomarkers will be identified in CPRD Aurum data (see codelist in appendix) and only measurements with an associated value will be included in analysis.
Objective 5: QRISK3 scores. These will be generated using either the algorithm published by LSHTM (https://datacompass.lshtm.ac.uk/id/eprint/1839/ - note currently only QRISK2 for GOLD published but full QRISK2/3 for GOLD and Aurum to be released shortly) or Manchester University (https://cran.r-project.org/web/packages/QRISK3/index.html).
Objective 6 primary outcome: MACE (composite of MI, stroke and CVD death). Secondary outcome: separately (a) MI, (b) stroke and (c) CVD death. MI and stroke will be identified using CPRD Aurum and HES APC and OP (see codelists in appendix) and deaths will additionally be identified using ONS death registrations where the primary cause is from the I chapter.
Jennifer Davidson - Chief Investigator - Health iQ Ltd ( UK ) t/a CorEvitas
Jennifer Davidson - Corresponding Applicant - Health iQ Ltd ( UK ) t/a CorEvitas
Archie Farrer - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Boglarka Kovacs - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Caoimhe Rice - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Gulsah Akin Unal - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Judith Ruzangi - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Mico Hamlyn - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Seth Jarvis - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Gulsah Akin Unal - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Townsend Index