Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer

Abstract

Abstract. Serum testosterone is a potential marker to distinguish between indolent and aggressive prostate cancer (PCa). The present study aimed to investigate whether low levels of total serum testosterone at diagnosis were associated with aggressive PCa and poor clinical outcomes. In total, 762 non-Hispanic Caucasian men with previously untreated PCa were recruited from The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were categorized into three groups based on their total serum testosterone levels according to clinical guidelines [low (<230 ng/dl), intermediate (230-350 ng/dl) and normal (>350 ng/dl)]. PCa aggressiveness (low-, intermediate-or high-risk, or metastatic) was compared using multinomial logistic regression. Rates of disease progression, mortality from any cause and PCa-specific mortality were compared using the multivariate Cox proportional hazards model. Testosterone levels significantly decreased as PCa aggressiveness increased (P<0.001). Compared with the normal testosterone group, the low testosterone group had 2.9-fold (OR, 2.92; 95% CI, 1.74-4.90; P<0.001), 5.6-fold (OR, 5.63; 95% CI, 3.14-10.12; P<0.001) and 72.4-fold (OR, 72.40; 95% CI,; P<0.001) increased risks of having intermediate-risk, high-risk and metastatic PCa, respectively. Furthermore, low levels of testosterone were significantly associated with a 10.7-fold (HR, 10.68; 95% CI, 1.35-84.44; P= 0.03) increased risk of PCa-specific mortality. The results of the present study indicate that low levels of total serum testosterone at diagnosis are associated with aggressive PCa and predict poor PCa-specific survival.

Low endogenous testosterone level is associated with high-risk prostate-specific antigen level in men with prostate cancer disease

“…In support of this finding is the observed strong negative correlation between PSA and TT among the patients with hypogonadism and highrisk PSA levels. These findings and observations in this study regarding the relationship between PSA and TT are in accord with the findings in similar studies by Alsharef et al, Garcia-Cruz et al, Schatzl et al, and Tu et al 6,9,10,16 Alsharef et al had investigated the association between serum TT and adverse prognostic features in men with prostate cancer and observed that low serum TT was associated with higher PSA, higher grade, locally advanced and metastatic prostate cancer. However, Alsharef et al had used the serum free testosterone in their study in contrast to the total serum TT employed in this study.…”

“…However, Tu et al posit that the low TT milieu in men might activate some oncogenic pathways that select for specific molecular features that are indicative of adverse or poor prognostic outcome. 16 While Loeb et al posit that the high or normal TT levels keep the prostate cells and early prostate cancer cells in a differentiated state and that the loss of this TT function secondary to low serum TT may lead to the development of less-differentiated cancer with adverse and poor prognostic features.…”

“…5 The challenge and debate had surfaced following the observation and report from various epidemiologic studies that low, rather than high, plasma TT level is associated with prostate cancer risk and the various adverse clinicopathologic and poor prognostic features of the disease. [6][7][8][9][10][11][12][13][14][15][16][17] In addition, in support of these studies is the fact that endogenous TT decreases with advancing age at the same time that prostate cancer incidence increases. 6 This recent observation has provoked several authors in various studies to suggest for a review of the decade-long norm of high TT association with prostate cancer.…”

“…6 This recent observation has provoked several authors in various studies to suggest for a review of the decade-long norm of high TT association with prostate cancer. [5][6][7][8][9][10][11][12][13][14][15][16][17] However, some other authors have questioned these recent assumptions of low, rather than, TT levels involvement in prostate cancer risk and these various adverse features of the disease. 5 Therefore, the relationship between endogenous TT and prostate cancer continues to be controversial and hence, merits further investigation.…”

Low testosterone at first prostate‐specific antigen failure and assessment of risk of death in men with unfavorable‐risk prostate cancer treated on prospective clinical trials

“…This stratification is supported by prior studies demonstrating that low testosterone at the time of PC diagnosis is associated with a poorer prognosis after radical prostatectomy or RT and ADT and shorter responses to salvage ADT. [15][16][17][18] If a high PSA response rate (such as a decline in pretreatment PSA of >80% or more stringently achieving an undetectable PSA <0.1 ng/mL) in at least two-thirds of the study cohort is observed, this would provide the basis to support a phase 3 trial in this setting investigating standard ADT with 1 novel agents and their impact on survival. Several points require further discussion.…”