A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer

Background: 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. Methods: 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. Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and andros-terone 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 dehydroepiandros-terone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 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; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054). Conclusions: 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. Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.