JU INSIGHT: Preoperative Circulating 11-Oxygenated Androgens and Metastasis-free Survival in Prostate Cancer
By: Cylia Dahmani, MSc; Patrick Caron, BSc; David Simonyan, MSc; Louis Lacombe, MD, MSc; Armen Aprikian, MD; Fred Saad, MD; Michel Carmel, MD; Simone Chevalier, PhD; Eric Lévesque, MD, PhD; Chantal Guillemette, PhD | Posted on: 16 Feb 2023
Dahmani C, Caron P, Simonyan D, et al. Preoperative circulating 11-oxygenated androgens are associated with metastasis-free survival in localized prostate cancer. J Urol. 2023;209(2):337-346.
Study Need and Importance
Prostate cancer relies primarily on circulating and intracellular biotransformation of circulating androgens for growth and progression. The circulating steroidome contains testicular and adrenal androgen precursors such as dehydroepiandrosterone available for intracrine androgen biosynthesis by cancer cells. The adrenal gland also produces noncanonical 11-oxygenated androgens such as the most abundant 11β-OH-androstenedione that is converted by enzymes expressed locally in prostate cancer cells and other tissues into highly potent androgen receptor ligands. These include the full agonists 11-ketodihydrotestosterone and 11-ketotestosterone, and the partial agonist 11β-hydroxydihydrotestosterone. We therefore studied the prognostic impact of these novel 11-oxygenated androgens in men with localized prostate cancer.
What We Found
We studied 7 adrenal 11-oxygenated precursors, potent 11-oxygenated androgens and their metabolites, and tested their relationship with clinical outcomes in the prospective PROCURE cohort composed of 1,783 men with newly diagnosed localized prostate cancer all undergoing radical prostatectomy (see Figure). We found that higher preoperative levels of the adrenal androgen precursor 11β-OH-androstenedione were associated with progressive disease, whereas the predominant bioactive 11-ketotestosterone and its metabolite 11-ketoandrosterone were associated with better metastasis-free survival. Furthermore, levels of 11-oxygenated androgens did not correlate with canonical circulating androgen receptor ligands such as testosterone and dihydrotestosterone.
Limitations are related to the number of metastatic events, which remain limited despite the cohort size and significant follow-up of nearly 94 months.
Interpretation for Patient Care
In men undergoing prostatectomy for localized disease, preoperative circulating 11-oxygenated androgen levels were associated with metastasis-free survival, a clinically relevant disease landmark associated with overall survival. Our findings may thus ultimately help personalized hormonal strategies for these patients.