Predictive Biomarkers and Personalized Medicine Serum Sex Steroids Depict a Nonlinear U-Shaped Association with High-Risk Prostate Cancer at Radical Prostatectomy

Purpose: To assess the association betweenpreoperative serum total testosterone (tT), 17b-estradiol (E2), sex hormone–binding globulin (SHBG), and tT–E2 ratio values with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network practice guidelines) at radical prostatectomy. Experimental Design: Serum E2, tT, and SHBG were dosed the day before surgery (7:00–11:00 am) in a cohort of 724 candidates to radical prostatectomy. Restricted cubic spline functions tested the association between predictors (i.e., model 1: age, bodymass index, and serum tT, E2, and SHBG levels; model 2: tT–E2 values instead of tT and E2 levels) and high-risk prostate cancer. Results: Low-, intermediate-, or high-risk prostate cancer was found in 251 (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the high-risk class showed the lowest tT, E2, and tT–E2 ratio values (all P 0.02). At univariate analysis, only age, tT, E2, and tT–E2 ratio values were significantly associated with high-risk prostate cancer (all P 0.006). At multivariate analyses considering model 1 variables, age (P 1⁄4 0.03), serum tT (all P < 0.001), and E2 (all P 0.01) were associated with high-risk prostate cancer; only tT–E2 ratios achieved independent predictor status for high-risk prostate cancer (all P < 0.001) when considering model 2. Both the lowest and the highest tT, E2, and tT–E2 values depicted a nonlinear U-shaped significant association with high-risk prostate cancer. Conclusions:These data showed that preoperative serumsex steroids are independent predictors of highrisk prostate cancer, depicting a nonlinear U-shaped association. Clin Cancer Res; 1–10. 2012 AACR.