UroToday.com – Until the development of androgen deprivation therapy (ADT), bilateral orchidectomy was the only way to achieve castration. Nowadays ADT can be considered a benchmark in the treatment of prostate cancer and it has been postulated that gonadotropin-releasing hormone (GnRH) agonists are able to reduce testosterone to obtain a level as low as bilateral orchidectomy. Different GnRH agonists are currently available. The purpose of the article is to evaluate the real role of the testosterone level in patients affected by prostate cancer and treated with ADT. We performed a non-systematic review of the literature and we identified 352 articles that subsequently were analyzed.

Various testosterone levels have been described to define castration, but to date 50 ng/dl is the most frequently used. This value derives from assay methods developed in the late 1960s with the use of the double-isotope derivate dilution technique but this cut-off point has not been updated, despite the availability of radioimmunoassay and chemiluminescence tests. A value of 20 ng/ml was proposed by an older edition of the NCCN guidelines on prostate cancer but it was not re-proposed in the subsequent versions. Specifically, castration levels as low as 50 ng/dl were reached in 95-98.9% of the patients using the classical leuproleide formulation, in 99-100% of those using the novel leuproleide formulation, and in 98.8% of those using triptorelin. Using such a breakpoint, only about 5% of patients being treated with GnRH agonist therapy fail to achieve castration. Applying the 20 ng/ml as cut-off point to define castration, 87-92%, 88-97.5%, and 96% of the patients receiving the classical leuproleide formulation, novel leuproleide formulation, and triptorelin reached castration, respectively.

On the whole, there are no prognostic factors useful to identify those patients who will not yield castration with GnRH agonists and, above all, the clinical relevance of the different levels of testosterone achieved during ADT is unknown because long-term data concerning the occurrence of androgen-independent prostate cancer and cancer-specific survival are not available. Further studies have to be performed to clarify these controversial issues.

Written by Giacomo Novara, MD and Silvia Secco, MD as part of Beyond the Abstract on UroToday.com.

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