DOWNSTAGING OF LOCALIZED PROSTATE-CANCER BY NEOADJUVANT THERAPY WITH FLUTAMIDE AND LUPRON - THE FIRST CONTROLLED AND RANDOMIZED TRIAL

Although the only opportunity to cure prostate cancer is treatment at an early stage, radical prostatectomy has remained relatively unpopula r because 40-50% of prostate cancers estimated at diagnosis as confine d to the prostate are found to be at a more advanced stage following h istopathological analysis of the surgical specimen. This first prospec tive, randomized trial investigated the potential advantages of 3-mont h neoadjuvant combination therapy with flutamide and lupron before rad ical prostatectomy vs. prostatectomy alone in early stage prostate can cer. Cancer-positive margins were reduced from 38.5% (25 of 65) in con trol patients to only 13.0% (10 of 77) in men who received neoadjuvant combination therapy with the antiandrogen flutamide and the luteinizi ng hormone-releasing hormone (LHRH) super-agonist Lupron before radica l prostatectomy (p = 0.006). Moreover, comparison of the final stage d etermined by histopathological examination of the surgical specimen wi th that estimated at diagnosis showed that a more advanced stage (upst aging) was found in 53.8% of controls, but patients who received combi nation therapy had an opposite effect: a more favorable stage than exp ected at diagnosis was found in 23.4% of cases (downstaging), a 77.2% advantage of neoadjuvant combination therapy. The concern about radica l prostatectomy, underestimation of stage, is thus markedly improved b y 3-month neoadjuvant therapy with flutamide and a LHRH superagonist. Cancer-negative margins are expected to be accompanied by a life expec tancy not different from that of men of similar age with no prostate c ancer; therefore, the present data, combined with efficient detection of early stage prostate cancer, offer the basis for dramatic improveme nt in the morbidity and mortality of prostate cancer.