Castration resistance and risk of bone metastases among men with nonmetastatic prostate cancer on androgen-deprivation therapy: A population-based cohort study from the Henry Ford Health System (HFHS) in Detroit, Michigan.

163 Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of metastatic prostate cancer (PC), but is frequently used in the non-metastatic (M0) setting. After a variable period of hormone sensitivity, most patients develop castration-resistant prostate cancer (CRPC). These men are at increased risk of developing bone metastases (BM), particularly in those with higher serum PSA and shorter PSA doubling time (DT). The epidemiology and natural history of M0 CRPC has not been well studied in a population-based setting. Methods: Using HFHS patient records, a retrospective cohort study was conducted among 723 men diagnosed with M0 PC between 1996 and 2005 (with follow-up [f/u] for outcomes through 12/31/2008), who received ADT, including 613 men with serial PSA measurements for CRPC determination. CRPC was defined as 2 consecutive PSA rises, with “high-risk” defined as PSA ≥ 8 ng/mL or PSA DT ≤ 10 months (mos) after the development of CRPC. The risk of subsequent BM was estimated for the overall cohort and for the CRPC and non-CRPC subsets. Results: The median age among patients in the study was 73 years, 48% were African American, and median f/u time after ADT initiation was 58 mos. 15% (n=93) met criteria for CRPC during f/u (with a median of 23 mos between ADT initiation and establishment of CRPC), with the majority considered being at high risk (n=81). Among the entire cohort, 74 men (10%) developed BM during f/u. The rate of BM was 4 times higher among CRPC patients compared to non-CRPC patients (p<0.001), with a median of 6 mos between CRPC and subsequent BM. No racial difference was observed with either the incidence of CRPC or BM. Conclusions: The HFHS resource allowed for investigation of disease progression in a racially diverse population. A substantial proportion of M0 PC patients on ADT will eventually develop CRPC and once castration-resistant, risk of BM is high.