In men with localized prostate cancer who underwent radical prostatectomy and were treated with a 5α-reductase inhibitor (5-ARI), earlier levels of circulating 11-oxygenated androgens may indicate disease progression or improved survival, a recent study found.
Specifically, “11-oxygenated adrenal androgen precursors were associated with progressive disease, while the bioactive 11-oxygenated androgen 11-ketotestosterone (11KT) and its metabolite 11-ketoandrosterone (11KAST) improved metastasis-free survival,” the researchers said.
A total of 1,793 treatment-naive patients and 155 who received preoperative treatment in the prospective PROCURE cohort, for whom preoperative plasma samples were collected before radical prostatectomy, were included in the analysis.
The researchers used liquid chromatography-tandem mass spectrometry to quantify adrenal 11-oxygen precursors, potent 11-oxygenated androgens, and their metabolites. They also examined circulation levels in relation to prognostic factors, disease-free survival, and metastasis-free survival using multivariable Cox proportional hazards models.
Of the patients, 583 had biochemical recurrence, 104 developed metastatic disease, and 168 died after surgery at a median follow-up of 93.8 months. Men with prostate-specific antigen >20 ng/ml and positive nodal status showed higher levels of 11-hydroxytestosterone and 11-ketotestosterone (p < 0.05). [J Urol 2023;209:337-346]
Multivariable analyzes revealed no significant association between 11-oxygenated androgens and disease-free survival. However, the major androgenic 11KT adrenal 11β-hydroxyandrostenedione and its metabolite 11KAST, modeled as quartiles, showed an association with metastasis-free survival (p=0.06, p=0.03, and p=0.008, respectively).
Notably, patients on 5-ARI presented a significant accumulation of 11-oxygenated androgen precursors and bioactive androgens but reduced levels of metabolites (p < 0.001).
“Our study establishes the potential prognostic value of plasma levels of adrenal-derived 11-oxygenated androgens in localized prostate cancer and highlights significant changes in circulating levels of 11-oxygenated androgens in radical prostatectomy associated with preoperative 5-ARI treatment,” the researchers said. .
“The adrenal androgen precursor 11β-hydroxyandrostenedione was associated with poorer metastasis-free survival, whereas the androgenic 11KT and its metabolite 11KAST were associated with better metastasis-free survival outcomes,” they added.
Previous studies supported the current finding of a link between higher levels of the full agonist 11KT and better outcomes, according to the researchers. Furthermore, the link between high levels of 11KAST metabolites and low metastatic incidence indicated that hepatic and peripheral androgen biotransformation may predict clinical outcomes after surgery even before treatment initiation.
In patients with localized prostate cancer, the development of metastasis was significantly associated with shorter overall survival. [J Clin Oncol 2017;35:3097-3104]
“These adrenal hormones are associated with progression to the metastatic stage here and, based on previous data generated in castration-resistant disease, 11-oxygenated androgens may sustain progression before and after initiation of androgen deprivation therapy,” the researchers said. [JCI Insight 2021;6:2021]
“Further studies focusing on this class of adrenal-derived 11-oxygenated androgens are needed to help capture the impact of these additional circulating hormones on disease progression in localized and metastatic castration-sensitive and castration-resistant diseases,” they noted.