ABSTRACT

Prostate cancer is the second most frequent malignant disease in men. Several therapeutic agents have been approved during the last decade. In this group of patients, serum testosterone levels are initially suppressed by anti-hormonal treatments for disease control. However, almost all patients eventually acquire resistance to anti-hormonal treatments, ending up with metastases. Radium-223 (Ra-223) (Xofigo®) is the first alpha-emitting radiopharmaceutical approved for the treatment of patients with metastatic castration-resistance prostate cancer (mCRPC) with bone metastases. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. The radiobiological effects of Ra-223 are mainly based on the direct damage to tumor-cell DNA via alpha particles. Thanks to their high linear energy transfer and a very short range, alpha particles produce a dense ionization around the disintegration site. The high linear energy transfer leads to cytotoxic effects that are independent of the oxygen concentration. Ra-223 has been demonstrated to prolong overall survival as well as to provide palliative pain relief and improved quality of life in patients with mCRPC with bone metastases in several studies, particularly in the phase III ALSYMPCA trial. This review focuses on the mechanisms and effectiveness of Ra-223 treatment, with emphasis on the contribution of current studies to our understanding and clinical practice.