Pathology of androgen deprivation therapy in prostate carcinoma. A comparative study of 173 patients

Background. Leuprolide, an agonist of luteinizing hormone-releasing hormone (LH-RH), and flutamide, an antiandrogen, increasingly are being used in the treatment of clinically localized prostate cancer. Only two small series (of 23 and 12 patients) have been published on the distinctive pathologic changes induced in the prostate by androgen deprivation therapy with discrepancies on the presence of squamous metaplasia, necrosis, and possible tumor destruction by combined androgen deprivation therapy. Methods. One hundred and thirteen radical prostatectomy specimens obtained after at least 3 months of leuprolide-flutamide androgen inhibition therapy and 60 nonhormonally treated prostates in randomly selected clinical Stage T2 prostate adenocarcinoma patients were entirely sectioned. Distinctive histologic findings were tabulated and their statistical value determined. Results. Resection margins of excision were involved by tumor in 43% of untreated and in 19% of androgen-deprived patients. Characteristic changes in androgen-inhibited nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layer, and squamous and transitional cell metaplasia. Prostatic intraepithelial neoplasia (PIN) was observed in 35% of treated patients. The presence of small tumor glands separated by stroma was the most frequently noted effect of androgen deprivation on prostate adenocarcinoma; pyknosis and branching empty spaces were less frequent. Large clear tumor cells within an inflammatory response was a third histologic pattern. Apparently unaltered tumor areas were observed in 43% of prostates exposed to androgen deprivation therapy. Conclusions. Androgen deprivation therapy result in histologically distinctive changes that can be recognized in both nonneoplastic and neoplastic prostate tissue. Residual tumor was present in all 113 treated radical prostatectomy specimens. In addition to glandular shrinkage, therapy was associated with statistically significant reductions in the frequency of high grade PIN and extension of cancer to prostate specimen margins of excisions. Cancer 1995;75:1634-41.