Histopathological effects of androgen deprivation in prostatic cancer

Thanks to earlier detection of clinically significant prostatic adenocarcinoma by measurement of serum prostate-specific antigen (PSA) levels, increasing numbers of patients are undergoing radical prostatectomy. However, the curative potential of this procedure is seriously limited by clinical understaging, which results in positive surgical margins and a marked increase in disease progression. In a multicenter study, histopathologic evaluation of radical prostatectomy specimens showed that presurgical androgen deprivation with leuprolide plus flutamide reduced the incidence of surgical margin involvement by 62%. In patients who received androgen deprivation therapy, characteristic and recognizable histopathologic changes in nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layers, and squamous and transitional cell metaplasia. Androgen deprivation markedly reduced the incidence of prostatic intraepithelial neoplasia (PIN) to 35%. The effects of androgen deprivation on prostatic carcinoma included smaller tumor glands, pyknosis and empty glandular spaces, and vacuolization and degeneration of tumor cells with an inflammatory response. Similar but less pronounced changes with no decrease in PIN were observed in finasteride-treated patients. It is important for pathologists to be aware of these histological changes and process tissue appropriately, because the changes affect the recognition and histological grading of tumors in radical prostatectomy specimens.