The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer.

BACKGROUND We examined the clinical relevance of skeletal-related events (SREs) for health state preferences, pain and health-related quality of life in patients with advanced prostate cancer and a history of bone metastases. PATIENTS AND METHODS Data were from a clinical trial of zoledronic acid versus placebo in the treatment of SREs associated with advanced prostate cancer metastatic to bone. Patients (n=248) were included if they experienced an SRE during the study. Outcome measures were assessed at fixed intervals. We used mixed-effects models to estimate changes in outcomes after each patient's first SRE. RESULTS There were clinically meaningful and statistically significant declines in physical well-being after: radiation and pathologic fractures; functional well-being after radiation; and emotional well-being after radiation and pathologic fractures. There also were meaningful and significant declines in preference and utility scores after radiation and fracture. Pain intensity declined after radiation, but not after other SREs; no other pain measure changed substantively. CONCLUSIONS SREs have important and significant effects on measures of health-related quality of life in men with prostate cancer. Treatments that prevent SREs may not demonstrate corresponding effects on outcomes if the effects of SREs occur between scheduled outcome assessments. Implications for trial design are discussed.