Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer.

Objectives Luteinizing hormone releasing hormone (LHRH) agonist therapy is one of the mainstays of prostate cancer treatment. Three dosing regimens currently exist: calendar-based, intermittent, and a testosterone (T)-based (T-based) regimen. We investigated the differences in development of early castrate resistance rates between these different regimens. Methods We evaluated 1617 patients with prostate cancer who received LHRH-agonist monotherapy in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006. Patients who had undergone surgery and/or radiation were excluded. Patients were grouped according to their dosing regimen: calendar-based, intermittent dosing, and T-based. Cox proportional hazard-regression analysis was used to estimate the hazards ratio (HR) for treatment failure. Results A total of 692 patients who received an LHRH agonist as primary monotherapy for prostate cancer fit our criteria. Calendar-based dosing was used in 325 patients; 252 received T-based dosing and 115 received intermittent dosing. On multivariate analysis controlling for demographic and prostate cancer–related variables, the T-based dosing group showed a significantly lower relative risk of treatment failure (HR = 0.65, P = .02). The intermittent-dosing group trended toward a lower risk treatment failure (HR = 0.80, P = .3). Among the variables analyzed, only a Gleason score >8 (HR = 2.05, P = .01) and a pretreatment prostate-specific antigen >20 (HR = 2.00, P <.01) were associated with a higher risk of treatment failure. Conclusions During the time period studied, T-based and intermittent dosing regimen of LHRH agonist had lower rates of early castrate resistance compared with standard calendar dosing, based on measurements for early androgen resistance.