Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer

Introduction: Testosterone suppression, or androgen-deprivation therapy (ADT), is an established treatment for recurrent and metastatic prostate cancer (PCa). Based on the accuracy and sensitivity of early assays (c. 1960-1970), the castrate testosterone level was set at <= 1.7 nmol/l. Improved sensitivity of testosterone assays shows that both surgical and medical castration can achieve levels < 0.7 nmol/l. However, the clinical implications and importance of maximum testosterone suppression remains a subject of controversy. This evidence-based review assesses prospective and retrospective clinical data, linking maximum suppression of testosterone with improved outcomes from ADT. Methods: PubMed and conference proceedings were searched for studies assessing the impact of low testosterone on clinical outcomes from ADT. The key search terms included combinations of prostate cancer and testosterone, predictive/prognostic, and androgen deprivation. Results were limited to studies investigating the relationship between testosterone levels and clinical outcomes. Results: Both prospective and retrospective data support a relationship between testosterone levels below the historical standard of 1.7 nmol/l and improved outcomes. Eight studies showed significant improvements in survival- related outcomes, with the majority of data supporting a testosterone level cutoff of <= 0.7 nmol/l. Conclusions: Tracking both testosterone and prostate- specific antigen (PSA) levels has significant clinical benefits, and the serum testosterone threshold of <= 0.7 nmol/l is a practical goal. The relative levels of testosterone and PSA may indicate continued hormone responsiveness or progression toward castration-resistant prostate cancer (CRPC) and should, therefore, inform treatment strategy. Standardization of assay methods and clinical coordination to facilitate widespread access to state-of the art laboratory equipment is necessary to ensure accurate decision-making.