Circulating estradiol, but not testosterone, is a significant predictor of high-grade prostate cancer in patients undergoing radical prostatectomy

Abstract

Background: The objective of this study was to assess the association between preoperative circulating levels of 17β-estradiol (E₂) and high-grade prostate cancer (HGPCa) (Gleason grade ≥ 4 + 3) at the time patients underwent radical retropubic prostatectomy (RRP).

Methods: Serum total testosterone (tT), sex hormone-binding globulin (SHBG), and E₂ levels were measured the day before surgery (8-10 AM) in a cohort of 655 consecutive Caucasian- European patients who underwent RRP at a single institution. Logistic regression models were used to test the association between predictors (including age, body mass index, prostate-specific antigen [PSA], clinical tumor classification, biopsy Gleason sum, tT, SHBG, and E₂) and HGPCa. Serum E₂ was included in the model as both a continuous variable and a categorized variable (according to the most informative cutoff: 50 pg/mL).

Results: Pathologic HGPCa was identified in 156 patients (23.8%). Patients with HGPCa had significantly higher PSA, clinical tumor classification, and biopsy Gleason sum than those without HGPCa (all P < .001). No other significant differences were observed between groups. At univariate analysis, continuously coded E(2) was not associated significantly with HGPCa (odds ratio [OR], 1.009; P = .25), whereas patients with E₂ levels ≥ 50 pg/mL had a 3.24-fold increased risk of HGPCa (P < .001). At multivariate analysis, E₂ was associated significantly with HGPCa both as a continuous predictor (OR, 1.02; P = .04) and as a categorical predictor (OR, 3.94; P < .001) after accounting for other variables. Conversely, tT and SHBG levels were not associated significantly with HGPCa.

Conclusions: E₂ was associated significantly with pathologic HGPCa, whereas SHBG and tT failed to demonstrate any association with HGPCa in patients who underwent RRP.