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 unpopular because 40-50% of prostate cancers estimated at diagnosis as confined to the prostate are found to be at a more advanced stage following histopathological analysis of the surgical specimen. This first prospective, randomized trial investigated the potential advantages of 3-month neoadjuvant combination therapy with flutamide and lupron before radical prostatectomy vs. prostatectomy alone in early stage prostate cancer. Cancer-positive margins were reduced from 38.5% (25 of 65) in control patients to only 13.0% (10 of 77) in men who received neoadjuvant combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) super-agonist Lupron before radical prostatectomy (p = 0.006). Moreover, comparison of the final stage determined by histopathological examination of the surgical specimen with that estimated at diagnosis showed that a more advanced stage (upstaging) was found in 53.8% of controls, but patients who received combination therapy had an opposite effect: a more favorable stage than expected at diagnosis was found in 23.4% of cases (downstaging), a 77.2% advantage of neoadjuvant combination therapy. The concern about radical prostatectomy, underestimation of stage, is thus markedly improved by 3-month neoadjuvant therapy with flutamide and a LHRH superagonist. Cancer-negative margins are expected to be accompanied by a life expectancy not different from that of men of similar age with no prostate cancer; therefore, the present data, combined with efficient detection of early stage prostate cancer, offer the basis for dramatic improvement in the morbidity and mortality of prostate cancer.
Endocrine Research Clinic, CHUL Research Center, Québec City, Québec.
F
F
Labrie
A
A
Dupont
L
L
Cusan
J
J
Gomez
P
P
Diamond
M
M
Koutsilieris
R
R
Suburu
Y
Y
Fradet
M
M
Lemay
B
B
Têtu
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005485:Flutamide / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
D005485:Flutamide; D016729:Leuprolide