Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why.

Radium-223 dichloride (223Ra) is the first, recently approved, α-particle-emitting radiopharmaceutical for the treatment of patients with bone metastases in castration-resistant prostate cancer (CRPC) and no evidence of visceral metastases. We explored MEDLINE, relevant congresses, and websites for data on 223Ra and prostate cancer therapies, focusing on therapeutic strategies and timing, bone metastases, and diagnostic assessment. 223Ra represents the only bone-targeting agent that has significantly extended patients' overall survival while reducing pain and symptomatic skeletal events. Unlike other radiopharmaceuticals, such as strontium-89 and samarium-153 EDTMP, 223Ra (11.4-days half-life) has shown a high biological efficiency mainly due to its short penetration range. These features potentially allow reduced bone marrow toxicity and limit undue exposure. 223Ra has been validated under the product name Xofigo® by the US Food and Drug Administration and the European Medicines Agency. Patient selection, management, and treatment sequencing is recommended to be discussed in the context of a multidisciplinary environment, including oncology, urology, nuclear medicine, and radiation therapy physicians. No consensus has been achieved regarding the optimal timing and its administration as single agent or in combination with zoledronic acid or chemotherapy, so far. This review aims to provide a rationale for the use of 223Ra in treating metastases from CRPC, highlighting the crucial role of a multidisciplinary approach, the disputed inclusion and exclusion criteria on the basis of agencies regulations, and the value of diagnostics for therapy assessment.