Preoperative Circulating 11-Oxygenated Androgens Are Associated With Metastasis-free Survival in Localized Prostate Cancer

Purpose: Adrenal 11-oxygenated androgens may support cancer progression in men with prostate cancer owing to their abundance and androgenic potential. We hypothesized that preoperative circulating levels of 11-oxygenated androgens influence clinical outcomes in men with newly diagnosed localized prostate cancer. Materials and Methods: We studied 1,793 treatment-naive patients and 155 patients who received preoperative treatment with 5 alpha-reductase inhibitors in the prospective PROCURE cohort, for which preoperative plasma samples were obtained prior to radical prostatectomy. Adrenal 11-oxygenated precursors, potent 11- oxygenated androgens and their metabolites (n=7), were quantified using liquid chromatography-tandem mass spectrometry. Circulating levels were evaluated in relation to prognostic factors, disease- free survival, and metastasis-free survival using multivariable Cox proportional hazards models. Results: At a median follow-up of 93.8 months after surgery, 583 patients experienced biochemical recurrence, 104 developed metastatic disease, and 168 deceased. Higher levels of 11-hydroxytestosterone and 11-ketotestosterone were observed in men with PSA >20 ng/mL and positive nodal status (P <.05). In multivariable analyses, no significant association between 11-oxygenated androgens and disease-free survival was observed. Adrenal 11 beta-hydroxyandrostenedione, the predominant androgenic 11-ketotestosterone, and its metabolite 11-ketoandrosterone, modeled as quartiles, were associated with metastasis-free survival (P =.06, P =.03, and P =.008, respectively). Significant accumulation of 11-oxygenated androgen precursors and bioactive androgens, but reduced metabolite levels, was observed in patients on 5a-reductase inhibitors (P <.001). Conclusions: Preoperative circulating 11-oxygenated androgen levels are associated withmetastasis-free survival in men with localized prostate cancer undergoing radical prostatectomy and are affected by 5a-reductase inhibitor treatment.

Automated summary

Preoperative circulating levels of 11-oxygenated androgens are associated with metastasis-free survival in men with localized prostate cancer undergoing radical prostatectomy and are influenced by 5α-reductase inhibitor treatment.