Preoperative Plasma Levels of Total Testosterone Associated with High Grade Pathology-Detected Prostate Cancer: Preliminary Results of a Prospective Study in a Contemporary Cohort of Patients

Abstract

Objectives: To investigate the associations, if any, between preoperative plasma levels of total testosterone (TT) and pathology Gleason score (pGS) in a contemporary cohort of prostate cancer (PCa) patients.

Materials and methods: Between November 2014 and June 2015, plasma levels of TT were measured in 142 patients who underwent radical prostatectomy. Exclusion criteria were as follows: 5α-reductase inhibitors, LH-releasing hormone analogues, or testosterone replacement treatment. The entire cohort, assessed by continuous and categorical variables, was classified into two groups according to the pGS that included low-intermediate (pGS 6-7) and high grade (pGS > 7) cases. TT was evaluated as a continuous variable.

Results: The cohort included 128 cases. High grade PCa was detected in 28 (21.8%) patients. Median plasma levels of both TT and prostate specific antigen (PSA) were significantly higher in these cases. In the clinical multivariate model, independent and positive predictors of pGS > 7 were TT (p = 0.041; OR = 1.004), PSA (p = 0.006; OR = 1.191), and bGS > 6 (p = 0.004; OR = 5.0); that is, a single unit increase in TT plasma levels increases the odds of having high grade PCa by 4%.

Conclusion: In a contemporary cohort of patients, preoperative plasma levels of TT directly and independently associated with high grade PCa. High baseline plasma levels of TT might have clinical applications for managing PCa. New and well designed prospective studies dealing with this subject are required.

Keywords: Hyptothalamus-pituitary-testis-prostate axis; Prostate cancer; Retropubic radical prostatectomy; Robot assisted radical prostatectomy; Testosterone.

Fig. 1

Median plasma levels of TT as a function of the pGS.

Fig. 2

Median TT plasma levels as a function of pT and stratified by pGS.

Fig. 3

The distribution of TT quartiles as percentage and stratified by the pGS in the study cohort. Legend: q1, TT < 266.5 ng/dL; q2, 266.5 ≤ TT < 331.5 ng/dL; q3, 331.5 ≤ TT < 408.25 ng/dL; q4, TT ≥ 408.25 ng/dL.

Fig. 4

The diffusion models explaining the sensitivity of high grade tumors to increased serum levels of TT. Low-intermediate cancers associate with model A in which the diffusion of TT from the blood (C1) to the prostate (C2) compartments is limited by the process of binding receptor saturation. High grade PCA associates with model B in which the diffusion between C1 and C2 is directly proportional to TT. Intermediate-high grade PCA associate with mode C which is a combination of models A and B. The diffusion curves of each model are also reported (for details see the discussion section).