DOWN-STAGING OF EARLY-STAGE PROSTATE-CANCER BEFORE RADICAL PROSTATECTOMY - THE FIRST RANDOMIZED TRIAL OF NEOADJUVANT COMBINATION THERAPY WITH FLUTAMIDE AND A LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST

Objective. To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer. Methods. A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy. Results. Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. Although, on average, the final stage determined by histopathologic examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8% of control patients, an opposite observation was made in the group of men who received the 3-month neoadjuvant combination therapy where the final stage, instead of being more advanced, was less advanced than at diagnosis in an average of 21.1% of men for a net 54% improvement of staging in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. Conclusions. Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.