Investigating cardiovascular health in prostate cancer patients undergoing hormonal therapy

Abstract

Prostate cancer is one of the most common cancers globally and in Hong Kong. For decades, hormonal therapy has served as the cornerstone treatment for prostate cancer, with continuous evolution in therapeutic options and guideline recommendations. However, global hormonal therapy utilization patterns in the context of evolving guidelines had not been previously described, particularly regarding the impact of the COVID-19 pandemic. Additionally, prostate cancer is increasingly recognized as a chronic disease characterized by slow disease progression and long overall survival, especially in patients diagnosed at early stages. In patients living with prostate cancer for extended periods, management of comorbidities becomes essential. Cardiovascular complications associated with hormonal therapy for prostate cancer have garnered particular interests from researchers. However, existing literature on hormonal therapy-related cardiotoxicity predominantly focused on Caucasian patients, while data on Asian population are scant and often contradictory. Moreover, evidence on effective management strategies for treatment-related cardiovascular side effects remains scarce. To address these knowledge gaps, global pharmaceutical sales data was used to characterize the global trend of hormonal therapy utilization. Three cohort studies were conducted to investigate cardiovascular health management in patients with prostate cancer. In the first study, electronic health records from Hong Kong and claims data from Taiwan were retrieved to assess the cardiovascular risks associated with hormonal therapy use for prostate cancer. The second study used healthcare data from Hong Kong to compare the cardiovascular safety profiles of androgen receptor pathway inhibitors, specifically abiraterone and enzalutamide, versus docetaxel, in patients with prostate cancer. In the third study, the primary cardioprotective effect of statin therapy in high-risk patients receiving hormonal therapy for prostate cancer was quantified using electronic health records from Hong Kong. The key findings in this thesis are as follows: (1) Global hormonal therapy consumption demonstrated modest growth relative to the overall prostate cancer treatment market between 2012 and 2022, characterized by sustained dominance of gonadotropin-releasing hormone agonists and a progressive decline in first-generate antiandrogen utilization, aligning with evolving clinical guideline recommendations. The COVID-19 pandemic highlighted vulnerabilities in pharmaceutical supply chains; (2) Use of hormonal therapy was associated with elevated cardiovascular risk; (3) Initiation of androgen receptor pathway inhibitors was associated with increased cardiovascular risk compared to docetaxel; and (4) Statin initiation was associated with reduced cardiovascular risks in high-risk patients with no history of cardiovascular disease and receiving hormonal therapy for prostate cancer. This research highlights the prostate cancer treatment-related cardiovascular safety concerns. For patients considered for hormonal therapy, including androgen receptor pathway inhibitors, comprehensive risk assessment prior treatment and systematic monitoring during therapy are essential for enhancing patient outcome. While the use of statins may provide primary prevention against hormonal therapy-related cardiotoxicity, future studies are required to confirm the benefit, determine the optimal regimen, and identify the patients who can benefit from the treatment.