Role of maximal androgen blockade in advanced prostate cancer

Androgen ablation by bilateral orchiectomy or by the administration of gonadotropin-releasing hormone (GnRH) agonists has become standard treatment for advanced prostate cancer. However, serum levels of dihydrotestosterone (DHT) remain at about 40% of the precastration levels due to the conversion of the adrenal androgens. Maximal androgen blockade (MAB) aims to block the stimulatory action of this adrenal-derived DHT by adding antiandrogens to surgical or medical castration. Some of the largest and best controlled randomized trials in Europe and the United States have shown statistically better progression-free survival, overall survival, and survival from death by prostate cancer with MAB than with monotherapy with a GnRH agonist or with bilateral orchiectomy. Trial 30853 of the European Organization for Research and Treatment of Cancer (EORTC) compared MAB using a combination of goserelin subcutaneous depot (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) and flutamide with bilateral orchiectomy. Some other published trials did not find the differences revealed by EORTC 30853, however, and so an overview or meta-analysis of trials on the effects of MAB was organized jointly by the American Cancer Society, the Urological Group of the EORTC, and the International Prostate Health Council. Preliminary results on some of the 23 trials included in the meta-analysis showed an advantage of the GnRH agonist therapy in combination with an anti-androgen, particularly in time to progression. If time to progression is viewed as improved quality of life due to the absence of symptoms, a net result in favor of the combination therapy is noted. The MAB trials, using flutamide as the antiandrogen, also showed a small but distinct improvement in survival with the combination treatment. An emphasis on prognostic factors allows treatment decisions to be reached more easily.