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.
Keywords: Castration; Immunoassay; Liquid chromatography tandem-mass spectrometry; Monitoring biomarker; Prostate cancer; Testosterone.
Copyright © 2022 Elsevier Inc. All rights reserved.