Oa. Armas et al., CLINICAL AND PATHOBIOLOGICAL EFFECTS OF NEOADJUVANT TOTAL ANDROGEN ABLATION THERAPY ON CLINICALLY LOCALIZED PROSTATIC ADENOCARCINOMA, The American journal of surgical pathology, 18(10), 1994, pp. 979-991
Neoadjuvant total androgen ablation therapy leads to involutional chan
ges in prostatic carcinoma and may have the potential to downstage ope
rable prostate cancers. We studied 27 clinically localized prostatic c
arcinomas after 3 months of combined treatment with a luteinizing horm
one-releasing hormone agonist, goserelin acetate, and the antiandrogen
flutamide, followed by radical retropubic prostatectomy, for changes
in the serum prostate-specific antigen (PSA) level, changes in prostat
ic volume, therapy-induced histopathologic changes, DNA ploidy, and pr
oliferative activity. Ten hormonally untreated, grade-matched prostati
c adenocarcinomas served as controls. The mean pretherapy serum PSA le
vel was 17.5 ng/ml, and posttherapy PSA levels were all <4.0 ng/ml, wi
th 18 men having undetectable levels. The mean reduction in prostatic
volume following hormonal therapy was 37% (range 16-52%). Pathologic s
taging confirmed 20 pT2NO, six pT3NO, and one pT3N1. All prostates sho
wed residual adenocarcinoma (extremely focal in seven cases [26%] with
loss of glandular architecture, cytoplasmic vacuolization, and nuclea
r pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormona
lly treated prostates and 80% of 10 untreated controls. Immunostaining
for proliferating cell nuclear antigen showed >10% nuclear reactivity
in 33% of treated carcinomas and 90% of untreated carcinomas. In conc
lusion, 3 months of neoadjuvant androgen ablation for localized prosta
tic carcinoma significantly lowers serum PSA and prostatic volume and
produces involutional changes in residual carcinomas that mimic high-g
rade disease. However, pretreated carcinomas have predominantly a dipl
oid DNA content and low proliferative activity as opposed to untreated
carcinomas. Thus, grading of pretreated adenocarcinomas by convention
al methods may be misleading. Preoperative total androgen ablation has
a profound effect on a subset of prostatic carcinoma cells, possibly
by facilitating programmed cell death.