Standard Dose Versus High Dose and Versus Extended Standard Dose Radium-223 Dichloride in Castration-resistant Prostate Cancer Metastatic to the Bone

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate

Castration-resistant disease defined as:

Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)
Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR
Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.
Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization

Exclusion Criteria:

History of visceral metastasis, or visceral metastases
Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
Central nervous system (CNS) metastases
Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the treatment period or follow-up
Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
Prior treatment with radium-223 dichloride
Prior systemic radiotherapy and hemibody external radiotherapy