Bone metastases from prostate cancer: Hormonal therapy

Abstract

The majority of patients diagnosed with prostate cancer develop bone metastases. If untreated, patients affected by bone metastases experience skeletal events, like bone fractures or spinal cord compression, which complicate the course of disease and can further shorten their life expectancy; furthermore, these events are usually associated with pain and other troublesome symptoms, which can seriously affect patients’ quality of life and become a cause of temporary or permanent disability. For these reasons, the treatment of bone metastases represents a main issue in the management of advanced prostate cancer. Hormonal therapy is the mainstay of treatment for prostate cancer and, namely, the most effective therapeutic approach in patients with bone metastases. Actually, several hormonal compounds are available in the management of advanced prostate cancer: inhibitors of gonadal androgen synthesis, inhibitors of adrenal androgen synthesis, and first and second generation of antiandrogens. These agents exert a good control of the disease in terms of both overall survival and reduction in the incidence and severity of skeletal adverse events. In hormone-naïve patients, luteinizing hormone-releasing hormone (LH-RH) agonists or antagonists can be used sequentially or in combination with first-generation antiandrogens; in castration-resistant prostate cancer (CRPC), a major role is played by new-generation antiandrogens and CYP17 inhibitors, and sequencing these novel drugs with chemotherapy is still an open issue. This chapter analyzes the hormonal therapies approved for the treatment of prostate cancer, focusing on the relative mechanism of action, safety, and therapeutic activity of each agent. The results achieved by hormonal therapies in large comparative trials and meta-analysis are reviewed, and the various options both in hormone-naïve and in CRPC patients are presented and critically discussed. A brief insight into the pharmacodynamics of drugs and molecular aspects of the disease is provided to support the rationale for a more "intelligent" use of these treatments or their combination or the development of novel therapeutic approaches.