Treatment Strategies in Advanced Prostate Cancer/Genitourinary Malignancies: The Use of Bisphosphonates Across the Continuum

Abstract

Abstract Context Patients with metastatic bone disease often have severe bone pain and debilitating skeletal complications. Bisphosphonates, including zoledronic acid, are widely used in the management of metastatic bone disease. Objective To summarise current insights into the use of zoledronic acid in patients with bone metastases secondary to genitourinary malignancies, including prostate cancer (PCa), renal cell carcinoma (RCC), and bladder cancer (BCa). In addition, the potential of bone marker measurements to guide treatment decisions in PCa will be discussed. Evidence acquisition This manuscript is based on presentations given at an educational session held during the 2nd World Congress on Controversies in Urology (CURy) in Lisbon, Portugal. Data were retrieved from original manuscripts, recent review papers, and abstracts on the use of zoledronic acid for treatment of bone metastases from PCa, RCC, or BCa and the potential of bone markers to facilitate treatment decisions in PCa. Evidence synthesis In patients with bone metastases secondary to PCa, RCC, and BCa enrolled in randomised, placebo-controlled trials, monthly zoledronic acid at 4mg significantly reduced the proportion of patients with at least one skeletal-related event (SRE) and delayed the onset of SREs compared with placebo. Although more research is warranted, zoledronic acid seems to improve overall survival in these patients. In addition, ongoing trials are evaluating the antitumour effect of zoledronic acid. Based on retrospective trials, biochemical markers of bone remodelling, including N-telopeptide of type I collagen, seem to identify metastatic PCa patients at high risk for SREs or death. Conclusions The use of zoledronic acid has been shown to be effective in reducing SREs in patients with bone metastases from genitourinary malignancies. Clinical trials are currently ongoing to evaluate whether zoledronic acid also has a direct antitumour activity in addition to its bone-preserving activity. Although well-designed, prospective, randomised trials are needed, bone marker measurements may be used as a tool to guide treatment decisions.