Radium-223 is an α-emitting radiopharmaceutical capable of inducing double strand DNA breaks in cancer cells while minimizing exposure to surrounding marrow. The use of radium-223 for the treatment of bone metastases relies on the chemical similarity to calcium and the ability of the α-radiation and the short-lived decay products of radium-223 to kill cancer cells. The short range of α-radiation reduces the damage to surrounding healthy tissue creating a more localized effect compared to other radionuclide therapies, such as strontium-89. This is an appropriate treatment for patients with symptomatic bone pain and non-visceral metastases. A phase III trial26 with radium-223 in symptomatic men with progressive mCRPC with or without prior docetaxel exposure and no evidence of visceral metastasis reported improvement in median survival; 14.9 months versus 11.3 months (HR=0.70; 95% CI: 0.58 to 0.83; p<0.001) in favor of radium-223 over placebo. Time to first skeletal-related event (SRE) improved from 9.8 month with placebo to 15.6 months with radium-223 (HR=0.66; 95% CI: 0.52 to 0.83; p<0.001). Significant improvements in QOL measurements were reported in the patients treated with radium-223. Of the 921 patients of this trial, those receiving treatment were given 6 intravenous injections with a dose of 50 kBq per kilogram of body weight every 4 weeks. Rates of grade 3 or 4 neutropenia and thrombocytopenia were low at 2.2% and 6.3%, respectively.26 As radium-223 targets bone only and is not associated with a PSA decline in a majority of patients, it is imperative for the clinician to carefully assess the patient on a monthly basis. Progression in non-bone sites is not infrequent during this six-month period of treatment. Given the lack of utility of PSA measurement in this space, the Panel recommends obtaining abdomen/pelvis CT imaging and chest x-ray even in the absence of symptoms prior to cycle four (of planned six monthly cycles) to assess for occult disease progression. Clinicians should also be advised against concurrent use of abiraterone acetate plus prednisone in combination with radium-223 given the association with a higher risk of skeletal related events.125