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

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, 20.89-250.89; 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.

Keywords: aggressiveness; androgen; progression; prostate cancer; survival; testosterone.

Figure 1.

Association between total serum testosterone levels in patients with prostate cancer and (A) tumor aggressiveness, (B) total Gleason score, (C) clinical stage of tumor and (D) PSA levels at diagnosis. Results are presented as the mean ± standard error. PSA, prostate-specific antigen.

Figure 2.

Association between total serum testosterone levels in patients with PCa who underwent radical prostatectomy and (A) total Gleason score, (B) pathological stage of the tumor and (C) seminal vesicle invasion. Results are presented as the mean ± standard error.

Figure 3.

Restricted cubic spline modeling for the association between total serum testosterone levels and (A) intermediate-risk or (B) high-risk/metastatic forms of PCa compared with the low-risk form of PCa. Four knots were used in the modeling and the 95th percentile (675 ng/dl) was chosen as the reference level. PCa, prostate cancer; CI, confidence interval.

Figure 4.

Unadjusted Kaplan-Meier estimator survival curves and HRs for the association between total serum testosterone levels and (A) disease progression, (B) mortality from all causes and (C) mortality due to prostate cancer. HR, hazard ratio; CI, confidence interval.