Associations of Pretreatment Serum Total Testosterone Measurements with Pathology-Detected Gleason Score Cancer

Abstract

Background and Objective: Prostate cancer is an endocrine-dependent tumor which is still under-investigated for physiopathology factors related to its natural history. The association of pretreatment total testosterone (TT) serum levels with prostate cancer is still a controversial topic. The objective of this study was to investigate potential associations and functional relationships of preoperative TT serum level and pathology-detected Gleason score (pGS). Materials and Methods: Pretreatment and pathological variables of 220 patients operated with radical prostatectomy were retrospectively reviewed. Age, prostate-specific antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score (bGS), pGS, TT and free testosterone were the continuous variables, while clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: ≤3+3, 3+4, >3+4), pathology Gleason pattern (pGP: ≤3+3, 3+4, >3+4), pathology stage (pT: pT2, pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin invasion by cancer (R-, R+) were the categorical variables. Statistical methods were computed for assessing associations of TT and pGS; moreover, simple and multiple linear regression analysis (SLRA and MLRA) were used for assessing functional relationships of TT and pGS. Results: High-grade tumors (pGS ≥8.0) were associated with bGS >6.0 (p < 0.0001), pGP ≥3+4 (p < 0.0001), P+ >0.31% (p = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent, PSA >6.27 μg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA >6.27 μg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09 (pGP ≥3+4 and pGS ≥8.0). On SLRA, pGS variation was significantly predicted by bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA, pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p = 0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001) showed independence in predicting pGS variation. The best model for predicting pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because the predictive coefficient increased to 0.32, which means that patients with TT >15.5 have a significantly higher estimated risk for high-grade pGS than patients with TT ≤15.5 nmol/l (OR = 1.31). Conclusion: In a patient population undergoing radical prostatectomy, increased pretreatment serum measurements of TT are associated with and functionally related to high-grade pGS; moreover, baseline TT together with bGS and PSA are important factors for predicting pGS and assessing high-grade tumors. Baseline TT serum levels might have prognostic potential for assessing treatment response for continuous as well as intermittent androgen deprivation therapy.

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

“…Other studies showed no association, 12,24 while Porcaro et al suggest a direct relation between testosterone levels and Gleason score, a result that opposes the findings described previously. 25 In our study, we evaluated 423 patients and tested two thresholds, 250 and 300 ng/dL, for the definition of hypogonadism. We used pathological findings from RP specimens in order to most accurately reflect tumor characteristics.…”

Testosterone Replacement Therapy in Hypogonadal Men Following Prostate Cancer Treatment: A Questionnaire-Based Retrospective Study among Urologists in Bavaria, Germany

“…Since testosterone suppression is regarded as a therapeutic option, testosterone supplementation is seen as contraindicated for patients with PCa because androgen depletion is meant to reduce tumor growth, whereas testosterone may support tumor progression. In fact, recent investigations on the association of pretreatment serum total testosterone could demonstrate in a population of 220 patients prior to radical prostatectomy that increased pretreatment serum measurements of total testosterone are associated with and functionally related to a high-grade pathologic Gleason score [9] . Moreover, baseline total testosteron together with the Gleason score at biopsy and PSA were important factors for predicting a pathologic Gleason score and assessing high-grade tumors.…”

Association between Basal Total Testosterone Levels and Tumor Upgrading in Low and Intermediate Risk Prostate Cancer

“…In the surgical specimen, it has been shown that basal levels of TT associate with high risk PCA and tumor upgrading [16][17][18] . The aim of the present study was to investigate potential associations of basal levels of TT with tumor upgrading in a contemporary cohort of low and intermediate-low risk PCA patients.…”