J Urol. 2022 Nov 14:101097JU0000000000003049. doi: 10.1097/JU.0000000000003049. Online ahead of print.
ABSTRACT
PURPOSE: Adrenal 11-oxygenated androgens may support cancer progression in men with prostate cancer (PCa) 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 PCa.
MATERIAL AND METHODS: We studied 1793 treatment-naïve patients and 155 patients who received preoperative treatment with 5α-reductase inhibitors (5-ARIs) in the prospective PROCURE cohort for which preoperative plasma samples were obtained prior to radical prostatectomy (RP). Adrenal 11-oxygenated precursors, potent 11-oxygenated androgens and their metabolites (n=7) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Circulating levels were evaluated in relation to prognostic factors, disease-free survival (DFS), and metastasis-free survival (MFS), using multivariable Cox proportional hazards models.
RESULTS: At a median follow-up time of 93.8 months after surgery, 583 patients experienced biochemical recurrence, 104 developed metastatic disease and 168 diseased. Higher levels of 11-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT) were observed in men with prostatic specific antigen (PSA) >20 ng/ml and positive nodal status (P<.05). In multivariable analyses, no significant association between 11-oxygenated androgens and DFS was observed. Adrenal 11β-hydroxyandrostenedione (11OHA4), the predominant androgenic 11KT, and its metabolite 11-ketoandrosterone (11KAST), modeled as quartiles, were associated with MFS (P=.06, .03, and 0.008, respectively). A significant accumulation of 11-oxygenated androgen precursors and bioactive androgens, but reduced metabolite levels, was observed in 5-ARIs patients (P<.001).
CONCLUSIONS: Preoperative circulating 11-oxygenated androgen levels are associated with MFS in men with localized PCa undergoing RP and are affected by 5-ARI treatment.
PMID:36373402 | DOI:10.1097/JU.0000000000003049
