Osteoprotective
therapies have become an essential component in the management of advanced
prostate cancer (PC) patients as bone
metastases (BMs) have a major impact on morbidity and mortality.
Denosumab is a fully humanized antibody targeting the receptor activator of nuclear factor κB
ligand (RANKL), which has been approved by the European Medicines Agency (EMA) in Europe and the United States (US) Food and Drug Administration (FDA) in the US for prevention of skeletal-related events (SREs) in patients with solid
tumors and BMs, including PC. The clinical settings in which PC patients should be treated with
denosumab are still discussed controversially. In a phase III study,
denosumab significantly delayed SREs compared with
zoledronic acid (ZA) in patients with metastatic
castration-resistant PC (CRPC). In addition,
denosumab showed superior effects on
pain and health-related quality of life (QoL) in these patients. In patients with nonmetastatic CRPC,
denosumab has been proven to significantly increase bone
metastases-free survival. However, no significant benefits on
cancer-specific and overall survival were observed and
denosumab was not approved by the US FDA and EMA in this context. The effectiveness of
denosumab in patients with
castration-sensitive PC (CSPC) and BMs is also under discussion, as clinical trials with ZA in these patients have not shown significant benefits. Clinical data on the use of
denosumab in CSPC are urgently needed.