Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Adv Clin Chem. 2022;108:73-104. doi: 10.1016/bs.acc.2021.07.007. Epub 2021 Aug 23.
Testosterone is an essential steroid hormone associated with a wide variety of biological processes in humans. In prostate cancer, androgen signaling is an important driver of tumor cell growth. Depletion of gonadal testosterone, achieved by surgical or chemical castration, prevents androgenic signaling and temporally reduces, stops or reverses tumor growth before inevitable progression to castration-resistant prostate cancer occurs. Additional treatment strategies targeting androgenic signaling have become available, although these are without curative intent. While circulating testosterone is also associated with disease risk and potential clinical utility, the main use in the clinical lab is monitoring adequate castration and subsequent resistance to therapy. Adequate castrate testosterone concentrations are currently based on over 50 year-old double-isotope derivative assays that are disputed in automated immunoassay (IA) analysis. The debate has been further fueled with the introduction of mass spectrometry-based assays for testosterone, offering a substantial increase in sensitivity and specificity. In this review, we discuss testosterone regulation and androgen deprivation therapy in prostate cancer. We provide an overview of the developments in testosterone analysis for monitoring adequate castration and resistance to therapy. Current clinical practice and future clinical utility will be discussed. Finally, clinical and research recommendations will be presented.
睾酮是一种与人类多种生物学过程相关的重要类固醇激素。在前列腺癌中,雄激素信号是肿瘤细胞生长的重要驱动因素。通过手术或化学去势来耗尽性腺睾酮,可以阻止雄激素信号,并在不可避免地发展为去势抵抗性前列腺癌之前暂时减少、停止或逆转肿瘤生长。针对雄激素信号的其他治疗策略已经可用,尽管这些策略没有治愈的意图。虽然循环睾酮也与疾病风险和潜在的临床应用相关,但在临床实验室中的主要用途是监测充分去势和随后对治疗的耐药性。目前,充分去势的睾酮浓度基于 50 多年前的双同位素衍生测定法,而这些方法在自动化免疫测定(IA)分析中存在争议。随着基于质谱的睾酮测定法的引入,这种争论进一步加剧,这种方法在灵敏度和特异性方面有了显著提高。在这篇综述中,我们讨论了前列腺癌中的睾酮调节和雄激素剥夺疗法。我们概述了用于监测充分去势和治疗耐药性的睾酮分析的发展。我们将讨论当前的临床实践和未来的临床应用。最后,将提出临床和研究建议。