Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer

Androgen deprivation has been the principal means of controlling advanced prostate cancer, but does not cure the disease and all patients ultimately progress if the tumor is not eliminated with definitive local therapy. It has been demonstrated that despite androgen deprivation with LHRH agonists or orchiectomy, prostate tissue and prostate cancer maintain levels of androgens which are more than adequate to stimulate the androgen receptor. These levels of androgen may continue to stimulate the receptor and allow both survival of tumor cells and induction of resistance by overexpression of the receptor. The presumption that standard androgen deprivation achieves the optimal level of androgen suppression for patients is based on the levels of androgen achieved with castration, which achieves relatively short term control of cancer in the majority of patients. The hypothesis of this study is that more effective suppression of the androgen axis through elimination of adrenal androgens and more effective suppression of conversion to dihydrotestosterone will lower intraprostatic androgen levels, minimizing activation of the androgen receptor and augmenting apoptosis. We propose to test this hypothesis in a prospective, randomized trial, administering neoadjuvant androgen deprivation therapy of different types prior to radical prostatectomy for patients with clinically localized prostate cancer for 3 months. Plan of therapy Patients with clinically localized (cT1-T2) prostate cancer, at intermediate-high risk for relapse who are candidates for radical prostatectomy will be treated with one of three regimens: * Goserelin with dutasteride * Goserelin with bicalutamide and dutasteride * Goserelin with bicalutamide and dutasteride and ketoconazole Patients will undergo radical prostatectomy 3 months after initiation of treatment. Preoperative and intraoperative biopsies of the prostate gland will be utilized for analysis of prostatic hormones, gene expression and apoptosis.