Assessment of testosterone and its fraction in patients with locally advanced prostate cancer and in patients with primary metastatic disease

Introduction: The assessment of serum concentration testosterone in patients with localized prostate cancer in the aspect of the development of aggressive features raises a number of controversies, remains still an unresolved research area with the results of studies trying to assess the importance of circulating androgens in prostate cancer are still not clear. The aim of the study was to determine whether preoperative levels of circulating androgens (testosterone and its free and bioavailable fractions) are correlated with tumor aggressiveness in patients with localized prostate cancer and metastatic disease Materials and Methods: The study involved 40 asymptomatic men, 98 men with benign prostatic hyperplasia and 129 male patients diagnosed with prostate cancer (PCa) (T1 – T2, irrespective of N and M). All patients had total PSA (tPSA), free PSA (fPSA), testosterone (TEST), SHBG and albumin levels measured before the treatment begun. For each of the subjects, the percentage of free PSA (f/tPSA), free (fTEST) and bioavailable testosterone (bioTEST) concentration, percentage of free (% fTEST) and bioavailable (% bioTEST) testosterone were calculated. Results: In patients with prostate cancer the significantly higher tPSA levels (p = 0.0001 and p = 0.0001), significantly lower albumin concentration (p = 0.0001 and p = 0.0001), and levels f/tPSA (p = 0.0001 and p = 0.0001) were found, compared to the group of asymptomatic men and BPH . In addition, in the group of patients with PCa, the lower levels of fTEST (p = 0.0004) and bioTEST (p = 0.0001), and their percentages (p = 0.0013 and p = 0.0001), as well as higher SHBG concentration (p = 0.0002) were observed compared to the asymptomatic males. Significantly higher fTEST (p = 0.0377) and bioTEST (p = 0.0447) concentration were found in patients with cT2c stage as compared to the cT2b stage. There were no significant differences in the levels of the parameters studied depending on the grade of malignancy according to Gleason score. The presence of distant and / or regional node metastases is associated with the significantly higher tPSA (p = 0.0001), and SHBG (p = 0.0039) concentrations and significantly lower levels of %fTEST (p = 0.0346) and %bioTEST (p = 0.0030). Patients who died within the five years (since diagnosis) had significantly higher tPSA (p = 0.0001) and SHBG (p = 0.0002), and significantly lower levels of %fTEST (p = 0.0018) and %bioTEST (p = 0.0003). The percentages of free and bioavailable testosterone and the bioTEST concentration showed a statistically significant downward trend and the SHBG concentration significantly increased with the increase of tPSA concentration in PCa patients. In patients in the cT2a + cT2b group, tPSA concentrations inversely correlated with %bioTEST (r = – 0.2633). There were no significant correlations between the studied hormones and tPSA in the group of patients with the worse prognosis (cT2c). Patients with GS < 7 presented also a significant correlation between tPSA concentration and the %bioTEST levels (r = – 0.2548). Conclusions: Significantly lower percentages of free and bioavailable testosterone are observed in prostate cancer patients with PSA concentration higher than 100 ng/ml, distant and/or regional node metastases and shorter overall survival. Lower percentages of free and bioavailable testosterone are associated with the elevated serum hormone binding globulin (SHBG) levels (up to 5 years).