EFFECT OF NEOADJUVANT ENDOCRINE THERAPY (COMBINED ANDROGEN BLOCKADE) ON NORMAL PROSTATE AND PROSTATIC-CARCINOMA - A RANDOMIZED STUDY

The morphologic changes induced by neoadjuvant combination endocrine t herapy were evaluated in prostatectomy specimens from patients diagnos ed with localized prostate cancer. These patients participated in a pr ospective, randomized clinical trial investigating the effect of 3 mon ths of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone. Ninety-six radical prostatectomy specimens processed according to the same protoc ol were evaluated without knowledge of prior treatment. Forty-seven pa tients were randomly assigned to the neoadjuvant combination therapy g roup and 49 to the control arm. Compared with the control group, sever al changes were strongly and significantly associated with exposure to neoadjuvant combination therapy. The nonmalignant prostatic tissue sh owed strong prominence and hyperplasia of the basal cell layer, accomp anied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer tissue, on the other hand, showed smaller nuc leoli (p < 0.001), cell vacuolization (p < 0.001), rare intraluminal c rystalloids (p < 0.001), higher Gleason grade (p < 0.001), lower preva lence of capsular penetration (p < 0.001), and less frequent invasion of the perineural spaces (p < 0.001) and surgical margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the treated group (p = 0.007). The present findings show that preoperative endocrine com bination therapy induces highly characteristic changes in both nonmali gnant and cancerous prostatic tissue. Furthermore, following endocrine treatment, the surgical margins are less likely to be involved by can cer and capsular penetration is reduced.