Testosterone levels in patients with metastatic prostate cancer treated with luteinizing hormone-releasing hormone therapy: prognostic significance?

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To determine if the testosterone level achieved with androgen-deprivation therapy (ADT) is directly related to survival and risk of death in men with metastatic prostate cancer, as agonistic analogues of luteinizing hormone-releasing hormones (LHRH) are indicated for palliative treatment of these patients, but there is no consensus about the utility of serum testosterone measurements during the follow-up, and their possible prognostic value. PATIENTS AND METHODS We retrospectively reviewed 129 consecutive patients with a histological diagnosis of metastatic bony-only prostate cancer and previously untreated with ADT. They were treated with 3 months of goserelin. Testosterone and prostate-specific antigen (PSA) levels were measured in all patients every 3 months for the duration of the follow-up. The following variables were recorded: age, stage, Gleason score, basal PSA level, basal testosterone level, PSA nadir, time to PSA nadir, testosterone after 6 months, testosterone nadir and time to testosterone nadir. Data were analysed using Cox’s proportional hazards models, with the primary endpoint being cancer-specific survival. RESULTS The mean (sd) basal PSA level was 185.8 (344.1) ng/mL, and the mean nadir PSA level 2.7 (8.6) ng/mL. The mean testosterone levels at baseline, 6 months and the nadir were 440 (200), 40 (40) and 21 (15) ng/dL. With a mean follow-up of 47.5 (29.7) months, 71 patients were dead (55%) and 78 were alive (45%) at the time of analysis. Statistical analysis using Cox’s model showed that in these patients the risk of death was directly correlated not only to Gleason score (P < 0.01) and to the 6-month PSA level (P < 0.01), but also to the 6-month serum testosterone level (hazard ratio 1.32, P < 0.05). CONCLUSION These results suggest a direct correlation between the risk of death and testosterone levels achieved during ADT. Based on the present results, lowering the testosterone level as much as possible should be the goal of ADT in patients with metastatic prostate cancer, as this might affect patient survival.