F. Labrie et al., DOWNSTAGING OF LOCALIZED PROSTATE-CANCER BY NEOADJUVANT THERAPY WITH FLUTAMIDE AND LUPRON - THE FIRST CONTROLLED AND RANDOMIZED TRIAL, Clinical and investigative medicine, 16(6), 1993, pp. 499-509
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.