Evolution of treatment options for patients with CRPC and bone metastases: bone-targeted agents that go beyond palliation of symptoms to improve overall survival.

Metastasis to bone represents an all-too-frequent complication of advanced-stage prostate cancer (PCa): 50% to 70% of these patients will ultimately develop this devastating complication. PCa preferentially metastasizes to bone, and the skeletal complications increase mortality and decrease quality of life. The clinical consequences of skeletal metastasis also include pain, skeletal-related events (SREs), and increased costs of therapy. Recent advances in our understanding of the mechanisms of metastasis and the physiologic changes that occur with it, together with the introduction of new treatments, are furthering our ability to combat this problem. In this review, we examine bone-targeted palliative agents, nontargeted systemic cytotoxic therapies, and bone-targeted agents that go beyond palliation to also potentially improve progression-free and overall survival. We specifically focus on post-treatment outcomes--including pain relief, decreased opioid use, improvement in quality of life, freedom from SREs or new bony metastases, and increases in overall survival--in men with symptomatic, metastatic PCa. Treatments discussed include varied drug classes, such as bisphosphonates and human monoclonal antibodies; beta-emitting radiopharmaceuticals; external beam radiotherapy; systemic chemotherapies; Src inhibitors; endothelin-A receptor antagonists; clusterin inhibitors; and alpha-emitting radiopharmaceuticals.