Bone metastases in advanced prostate cancer. Management

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receiving abiraterone, whether the addition of Ra-223 might be safe and yield clinical
benefit is not yet established. If such an approach is chosen, patients should also be
receiving a bone-modifying agent, such as zoledronic acid or denosumab. (See
'Radium-223-based combinations' above.)
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Role of osteoclast inhibitors
• For men with CRPC and bone metastases, an osteoclast inhibitor (denosumab or
zoledronic acid) is indicated to prevent or delay skeletal complications in patients with
bone metastases. For many patients, denosumab may be preferred over zoledronic
acid, based on superior efficacy in a large randomized comparative trial. However,
others prefer zoledronic acid because there are sufficient data in CRPC to support
dosing every 12 rather than every 4 weeks. Zoledronic acid may also be a preferred
alternative if cost and/or reimbursement are important considerations. Data on
efficacy of bisphosphonates, denosumab, and comparative efficacy in men with CRPC
are discussed in detail elsewhere. (See "Osteoclast inhibitors for patients with bone
metastases from breast, prostate, and other solid tumors", section on 'Efficacy and
dosing considerations for individual agents'.)
Both agents should be dosed at bone-metastasis-indicated dosing (denosumab 120 mg
subcutaneously every four weeks, zoledronic acid 4 mg intravenous every three to four
weeks). (See 'Castration-resistant disease' above.)
Although there are sufficient data in men with CRPC to support dosing of zoledronic
acid every 12 weeks rather than every 4 weeks for most men we still prefer every-4-
week dosing, at least initially, for patients with extensive or highly symptomatic bone
metastases, including all patients who are receiving Ra-223. Specific recommendations
are provided separately. (See "Osteoclast inhibitors for patients with bone metastases
from breast, prostate, and other solid tumors", section on 'Dosing interval'.)
• For men with bone metastases and castration-sensitive prostate cancer, we suggest
against the use of osteoclast inhibitors to prevent or delay complications from bone
metastases (Grade 2B). (See 'Castration-sensitive disease' above.)
• We also suggest against the use of osteoclast inhibitors to prevent or delay the
appearance of bone metastases in men with high-risk nonmetastatic prostate cancer
(Grade 2B). (See 'Prevention or delay of bone metastases' above.)
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