CLINICAL AND PATHOBIOLOGICAL EFFECTS OF NEOADJUVANT TOTAL ANDROGEN ABLATION THERAPY ON CLINICALLY LOCALIZED PROSTATIC ADENOCARCINOMA

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.