BIOCHEMICAL AND PATHOLOGICAL EFFECTS OF 8 MONTHS OF NEOADJUVANT ANDROGEN WITHDRAWAL THERAPY BEFORE RADICAL PROSTATECTOMY IN PATIENTS WITH CLINICALLY CONFINED PROSTATE-CANCER

Purpose: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific an tigen (PSA) to reach its nadir, evaluate the ability of an ultrasensit ive assay to measure decreases in PSA less than 0.2 mu g./l., and char acterize the effects of 8 months of neoadjuvant therapy on pathologica l stage, positive margin rates, proliferation and tumor marker immune- staining. Materials and Methods: We evaluated 50 patients with clinica lly localized prostate cancer treated by 8 months of reversible androg en ablation before radical prostatectomy. Serum PSA and testosterone l evels were measured monthly. Results: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrase nsitive assay, serum PSA decreased to undetectable levels (less than 0 .1 mu g./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margi n rate was 4%. Of the cases 68% were organ-confined and 24% were speci men-confined. The positive margin rate was not increased after reevalu ation with cytokeratin, PSA and prostatic acid phosphatase immune-stai ning but of 4 cases initially staged as PO on hematoxylin and eosin ev aluation 2 had microscopic foci of cancer with prostatic acid phosphat ase staining. Immune-staining with the proliferation markers prolifera tion cell nuclear antigen and Ki-67 showed decreased staining in surgi cal specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develo p during prolonged neoadjuvant therapy. Conclusions: Eight months of n eoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, whil e the ongoing slower decrease reflects decreasing tumor volume.