Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer 1

The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecting PSA levels. As bone metastases develop, factors derived from bone metabolism are released into blood and urine, including N- and C-terminal peptide fragments of type 1 collagen and bone-specific alkaline phosphatase, which represent potentially useful biomarkers for monitoring metastatic bone disease. A number of clinical trials have investigated these bone biomarkers with respect to their diagnostic, prognostic, and predictive values. Results suggest that higher levels of bone biomarkers are associated with an increased risk of skeletal-related events and/or death. As a result of these findings, bone biomarkers are now being increasingly used as study end points, particularly in studies investigating novel agents with putative bone effects. Data from prospective clinical trials are needed to validate the use of bone biomarkers and to confirm that marker levels provide additional information beyond traditional methods of response evaluation for patients with metastatic prostate cancer.