Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate.
BACKGROUND
It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer.


METHODS
Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated.


RESULTS
Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3.


CONCLUSIONS
The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior to radiation therapy. Although our clinical experience is preliminary, combined androgen ablation and radiation therapy may also be effective in controlling locally advanced prostate cancer, with tolerable side-effects.
Hara
Isao
I
Department of Urology, Kobe University School of Medicine, Japan. hara@med.kobe-u.ac.jp
Miyake
Hideaki
H
Yamada
Yuji
Y
Takechi
Yoshizumi
Y
Hara
Shoji
S
Gotoh
Akinobu
A
Fujisawa
Masato
M
Okada
Hiroshi
H
Arakawa
Soichi
S
Soejima
Toshinori
T
Sugimura
Kazuro
K
Kamidono
Sadao
S
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery*; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D016729:Leuprolide