Background: In patients with advanced prostate cancer, medical castration remains a mainstay of treatment. A testosterone level below 50 ng/dL has been previously accepted as an adequate level of androgen suppression and remains the benchmark level for clinical trials. However, there is mounting evidence that lower testosterone levels may be associated with improved clinical outcomes. We evaluated our cohort of patients with advanced prostate cancer to assess the impact of testosterone suppression on progression to castrate resistant prostate cancer (CRPC).
Methods: Patient data was obtained from a prospective database of patients undergoing androgen deprivation therapy (ADT) at a tertiary centre from 2006-2011. A total of 39 patients were eligible for inclusion with at least 12 months follow-up. Patients were administered LHRH agonists or antagonist with testosterone and PSA assessments every 3 months. Patients were considered to have progressed to CRPC when there were at least 2 consecutive rises in PSA above nadir, clinical progression, or death from disease. Patients were stratified into two risk groups based on 6-month absolute and 1-year mean testosterone levels following initiation of ADT. Baseline characteristics between risk groups were compared using the Student’s t-test and chi-squared test. Probability of disease progression was assessed using the Kaplan-Meier method and compared using the log-rank test.
Results: Median patient follow up was 2.3 years with 38% free of disease at last follow up. Patients with 6-month absolute testosterone less than 32 ng/dL had an increased time to CRPC (log rank p=0.06). Patients with 1-year mean testosterone less than 32 ng/dl had a significantly increased time to CRPC (log rank p=0.005). Patients did not differ significantly in their baseline characteristics.
Conclusions: Adequate testosterone suppression during ADT may play a clinically significant role in delaying CRPC. While PSA levels are often used to assess for response to ADT, the current study suggests testosterone level in the first year following initiation of ADT may serve as an early predictor of disease progression.