Neoadjuvant hormonal therapy: the Canadian experience.
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 on histopathologic findings at surgery and serum prostate-specific antigen (PSA).


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. A net 54% improvement of staging was observed 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. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL.


CONCLUSIONS
Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.
Labrie
F
F
Prostate Cancer Research Unit, Centre Hospitalier Universitaire de Québec (CHUQ), Laval University Medical Center, Canada.
Cusan
L
L
Gomez
J L
JL
Diamond
P
P
Suburu
R
R
Lemay
M
M
Tetu
B
B
Fradet
Y
Y
Bélanger
A
A
Candas
B
B
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D002170:Canada; D017024:Chemotherapy, Adjuvant; D004359:Drug Therapy, Combination; D005485:Flutamide / Q000627:therapeutic use*; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide; D017430:Prostate-Specific Antigen