The importance of testosterone control in prostate cancer

Objectives: This article outlines the role of testosterone in prostate cancer (PCa) homeostasis and describes the effect of androgen-deprivation therapy (ADT) by luteinising hormone-releasing hormone (LHRH) agonists on PCa. In addition, the outcome and benefits of medical versus surgical castration are evaluated. Methods: This paper is based on a presentation during a satellite symposium held at the European Association of Urology 2007 annual meeting. Relevant articles on testosterone importance and hormonal control in PCa were selected from literature databases. Results: The goal of ADT is to induce a rapid, profound, and sustained suppression of testosterone. The testosterone threshold to trigger apoptosis is not yet known; therefore, it is hypothesised that it is better to achieve lower testosterone values. Historically, it has been assumed that ADT succeeds if testosterone levels reach a threshold of 50 ng/dl or lower. However, surgical castration, which remains the "gold standard", achieves lower testosterone values, closer to 20 ng/dl. Analysis of clinical trials with conventional LHRH agonists shows that these agents fail to reduce testosterone to <= 50 ng/dl in 1-12.5% of the patients, whereas 13-40% of the cases do not achieve testosterone levels <= 20 ng/dl. Furthermore, the incidence of miniflares to repeat injections varies around 10%, whereas breakthrough responses occur in 2-24% of the patients. Conclusions: Conventional LHRH agonists do not induce profound and sustained testosterone suppression in all patients, similar to orchidectomy. To give patients maximum benefit from medical castration via LHRH agonist treatment, we must have new formulations. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.