Zoledronic acid in metastatic castrate-sensitive prostate cancer: A state-of-the-art review

Prostate cancer is the most common cancer in men in developed countries. Despite its slow growing pattern, metastatic disease to bone occurs and results in a significant number of deaths. Since more than eight decades, the classical androgen deprivation therapy (ADT) leads to clinical response in most patients with metastatic castration-sensitive prostate cancer (mCSPC). Moving backward docetaxel and androgen receptor pathway inhibitors (ARPI) from castrate-resistant setting to castrate sensitive setting improves overall survival (OS) compared to ADT alone. Recently, studies suggested that triplet therapy by adding ARPIs such as abiraterone acetate or darolutamide to ADT + docetaxel is more effective than ADT/docetaxel alone in patients with high-volume mCSPC. Although the scientific progress during the last decade, has led to improvements in outcome for patients with mCSPC, there are still several areas impacting daily practice, for which high-level evidence is lacking, especially for adding monthly zoledronic acid in this setting. We structured this review by conducting a comprehensive analysis of the existing literature. This manuscript reviews both the benefits and potential harms of zoledronic acid in the treatment of mCSPC and provides conclusions on the criteria for its use, and the possible use of alternative bone protecting agents (BPA).