For about 50 years,
androgen blockade in
prostate cancer has been limited to monotherapy (surgical
castration) or high doses of
estrogens in patients with advanced disease and bone
metastases. The discovery of medical
castration with
LHRH agonists has led to fundamental changes in the endocrine
therapy of
prostate cancer. In 1979, the first
prostate cancer patient treated with an
LHRH agonist received such treatment at the Laval University Medical Center. A long series of studies have clearly demonstrated that medical
castration with an
LHRH agonist has inhibitory effects on
prostate cancer equivalent to those of surgical
castration. The much higher acceptability of
LHRH agonists has been essential to permit a series of studies in localized disease. Based upon the finding that the testicles and adrenals contribute approximately equal amounts of
androgens in the human prostate, the combination of medical (
LHRH agonist) or surgical
castration associated with a pure
antiandrogen (
flutamide,
nilutamide or
bicalutamide) has led to the first demonstration of a
prolongation of life in
prostate cancer, namely
a 10-20% decreased risk of death according to the various metaanalyses of all the studies performed in advanced disease. In analogy with the other types of advanced
cancers, the success of combined
androgen blockade in metastatic disease is limited by the development of resistance to treatment. To avoid the problem of resistance to treatment while taking advantage of the relative ease of diagnosis of
prostate cancer at an "early" stage, the much higher acceptability of
LHRH agonists has permitted a series of studies which have demonstrated a major reduction in deaths from
prostate cancer ranging from 31% to 87% at 5 years of follow-up in patients with localized or locally advanced
prostate cancer. Most importantly, recent data show that the addition of a pure
antiandrogen to an
LHRH agonist in order to block the
androgens made locally in the prostate leads to a 90% long-term control or probable cure of
prostate cancer.