Centre Hospitalier Universitaire (CHU) de Québec Research Centre and Faculty of Medicine, Laval University, Québec, Canada.
CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, Canada.
Cancer Epidemiol Biomarkers Prev. 2019 Apr;28(4):701-706. doi: 10.1158/1055-9965.EPI-18-1002. Epub 2019 Feb 7.
In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression.
The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.
The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 ( = 0.0017; q = 0.026) and 1.24 ( = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; = 0.057) and DHEA-S levels (HR = 1.43; = 0.054).
In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.
The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.
在接受根治性前列腺切除术（RP）的局限性前列腺癌男性中，其全身激素环境是否与预后相关尚不确定。本研究旨在探讨循环类固醇代谢组与预后因素和进展的关系。
前瞻性 PROCURE 队列于 2007 年至 2012 年招募，包括 1766 名接受 RP 前提供血液样本的局限性前列腺癌患者。采用质谱法测量血浆中 15 种类固醇的水平，并采用逻辑回归和多变量 Cox 比例风险模型确定其与预后因素和无病生存率（DFS）的关系。
术后中位随访时间为 73.2 个月。总体而言，524 例患者发生生化失败，75 例患者发生转移性疾病。低危疾病的睾酮和雄酮水平较高。肾上腺前体与癌症进展风险之间存在关联。在高危患者中，log 转化的雄烯二酮（A5diol）和脱氢表雄酮硫酸酯（DHEA-S）水平每增加一个单位，DFS 的 HR 分别为 1.47（ = 0.0017；q = 0.026）和 1.24（ = 0.043；q = 0.323）。尽管转移性事件的数量有限，但观察到 A5diol（HR = 1.51； = 0.057）和 DHEA-S 水平（HR = 1.43； = 0.054）与无转移生存的趋势。
在局限性前列腺癌男性中，我们的数据表明术前类固醇代谢组与高危疾病复发的风险相关。
肾上腺雄激素与局限性高危疾病进展的相关性可能有助于为这些患者制定激素策略。
