Dahmani Cylia, Caron Patrick, Simonyan David, Lacombe Louis, Aprikian Armen, Saad Fred, Carmel Michel, Chevalier Simone, Lévesque Eric, Guillemette Chantal
Centre de recherche du Centre Hospitalier Universitaire de Québec-Université Laval (CRCHUQc-UL), Centre de recherche en cancer (CRC) de l'Université Laval, Quebec City, Québec, Canada.
Faculty of Pharmacy, Université Laval, Quebec City, Québec, Canada.
J Urol. 2023 Feb;209(2):337-346. doi: 10.1097/JU.0000000000003049. Epub 2022 Nov 14.
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.
We studied 1,793 treatment-naïve patients and 155 patients who received preoperative treatment with 5α-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.
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 ( < .05). In multivariable analyses, no significant association between 11-oxygenated androgens and disease-free survival was observed. Adrenal 11β-hydroxyandrostenedione, the predominant androgenic 11-ketotestosterone, and its metabolite 11-ketoandrosterone, modeled as quartiles, were associated with metastasis-free survival ( = .06, = .03, and = .008, respectively). Significant accumulation of 11-oxygenated androgen precursors and bioactive androgens, but reduced metabolite levels, was observed in patients on 5α-reductase inhibitors ( < .001).
Preoperative circulating 11-oxygenated androgen levels are associated with metastasis-free survival in men with localized prostate cancer undergoing radical prostatectomy and are affected by 5α-reductase inhibitor treatment.
肾上腺11-氧化雄激素可能因其丰富性和雄激素潜力而促进前列腺癌男性患者的癌症进展。我们假设，术前循环中11-氧化雄激素水平会影响新诊断的局限性前列腺癌男性患者的临床结局。
我们在PROCUR队列研究中纳入了1793例未经治疗的患者以及155例接受术前5α还原酶抑制剂治疗的患者，该队列研究为前瞻性研究，在根治性前列腺切除术之前采集了术前血浆样本。使用液相色谱-串联质谱法定量测定肾上腺11-氧化前体、强效11-氧化雄激素及其代谢物（共7种）。使用多变量Cox比例风险模型评估循环水平与预后因素、无病生存期和无转移生存期之间的关系。
术后中位随访93.8个月时，583例患者出现生化复发，104例发生转移，168例死亡。在前列腺特异性抗原（PSA）>20 ng/mL且淋巴结转移阳性的男性患者中观察到较高水平的11-羟基睾酮和11-酮睾酮（P<0.05）。在多变量分析中，未观察到11-氧化雄激素与无病生存期之间存在显著关联。将肾上腺11β-羟基雄烯二酮、主要雄激素11-酮睾酮及其代谢物11-酮雄甾酮按四分位数建模，它们与无转移生存期相关（分别为P=0.06、P=0.03和P=0.008）。在接受5α还原酶抑制剂治疗的患者中观察到11-氧化雄激素前体和生物活性雄激素显著蓄积，但代谢物水平降低（P<0.001）。
术前循环中11-氧化雄激素水平与接受根治性前列腺切除术的局限性前列腺癌男性患者的无转移生存期相关，并受5α还原酶抑制剂治疗的影响。
