Hoare Dylan, Skinner Thomas A A, Black Angela, Robert Siemens D
Department of Urology, Centre for Applied Urological Research, Queen's University, Kingston, ON;
Departments of Urology and Oncology, and Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Queen's University, Kingston, ON.
Can Urol Assoc J. 2015 Mar-Apr;9(3-4):122-7. doi: 10.5489/cuaj.2545.
Treatment of advancing prostate cancer focuses on blocking the activation of the androgen receptor with resultant prolonged perturbation of the hypothalamic-pituitary-gonadal axis. Androgen deprivation therapy (ADT) is marked, however, by eventual progression to castration- resistant prostate cancer (CRPC). Emerging evidence has postulated that follicle-stimulating hormone (FSH) may lead to proliferative and mutagenic responses of prostate cancer. We investigated the association of serum FSH and time to castration resistance.
This was a single-centre retrospective study assessing serum FSH levels of patients undergoing ADT for advancing prostate cancer. The primary outcome was time of ADT initiation to the development of CRPC. For each patient on treatment and with castrate levels of testosterone, the maximum FSH value between ADT commencement and CRPC was identified and recorded. FSH was analyzed as a continuous and categorical variable. Cox multivariate regression in a step-wise fashion was used to explore the association between FSH levels and time to CRPC.
From a database of 323 prostate cancer patients actively managed with ADT, 103 men had a documented FSH value while castrate, with 45 men progressing to CRPC. The mean ± standard deviation maximum FSH value of these patients was 6.66 ± 4.22 mIU/mL (range: 1.5-28.1). The mean duration from ADT commencement to CRPC was 3.03 ± 0.34 years (range: 0.36-9.71). Univariate analysis suggested a trend of a negative correlation between FSH values and time to castrate resistance. A FSH value of less than or equal to the lowest tertile (4.8 mIU/mL) was associated with a longer time to CRPC (hazard ratio 0.46; p = 0.006). In the Cox regression analysis, elevated FSH was associated with a shorter duration time to CRPC (p = 0.03).
This retrospective, single-centre study would suggest there may be an association between serum FSH levels and time to CRPC for men treated palliatively with ADT for advancing prostate cancer. Further clinical investigation in a larger cohort of men is required to determine any clinical utility of FSH as a biomarker of progression or target for therapy.
晚期前列腺癌的治疗重点在于阻断雄激素受体的激活,从而导致下丘脑 - 垂体 - 性腺轴的长期紊乱。然而,雄激素剥夺疗法(ADT)最终会进展为去势抵抗性前列腺癌(CRPC)。新出现的证据表明,促卵泡生成素(FSH)可能导致前列腺癌的增殖和致突变反应。我们研究了血清FSH与去势抵抗时间的关联。
这是一项单中心回顾性研究,评估接受ADT治疗晚期前列腺癌患者的血清FSH水平。主要结局是从ADT开始到CRPC发生的时间。对于每个接受治疗且睾酮处于去势水平的患者,确定并记录ADT开始至CRPC期间的最大FSH值。FSH作为连续变量和分类变量进行分析。采用逐步Cox多变量回归来探讨FSH水平与至CRPC时间之间的关联。
在一个由323例接受ADT积极治疗的前列腺癌患者组成的数据库中,103名男性在去势状态下有记录的FSH值,其中45名男性进展为CRPC。这些患者的平均±标准差最大FSH值为6.66±4.22 mIU/mL(范围:1.5 - 28.1)。从ADT开始到CRPC的平均持续时间为3.03±0.34年(范围:0.36 - 9.71)。单变量分析表明FSH值与去势抵抗时间之间存在负相关趋势。FSH值小于或等于最低三分位数(4.8 mIU/mL)与至CRPC的时间更长相关(风险比0.46;p = 0.006)。在Cox回归分析中,FSH升高与至CRPC的持续时间缩短相关(p = 0.03)。
这项回顾性单中心研究表明,对于接受ADT姑息治疗的晚期前列腺癌男性患者,血清FSH水平与至CRPC时间之间可能存在关联。需要在更大规模的男性队列中进行进一步的临床研究,以确定FSH作为疾病进展生物标志物或治疗靶点的任何临床实用性。