Predictors of Clinical Metastasis in Prostate Cancer Patients Receiving Androgen Deprivation Therapy

BACKGROUND: Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate-resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT. METHODS: Of the 13,740 men with biopsy-proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi-square tests in a Cox proportional hazards regression model. RESULTS: The mean age of the men in the cohort was 70 years (range, 39-94 years). One hundred ninety-one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1-139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P <.0001), percent of biopsies positive >33% (HR, 3.36; P =.003), age <= 65 years at diagnosis (HR, 2.11; P =.001, and prostate-specific antigen velocity on ADT (HR, 1.04; P <.001) were found to be significantly associated with the development of metastatic disease after ADT. CONCLUSIONS: Younger men with high-risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate-resistant disease. Cancer 2009;115:4470-6. (C) 2009 American Cancer Society.