Pathological changes in benign and malignant prostatic tissue following androgen deprivation therapy.

Several retrospective studies, as well as prospective trials, have demonstrated that neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancer. Following androgen deprivation therapy, virtually all prostates contain residual adenocarcinoma, although it may be extremely focal in up to 25% of cases. Morphological changes observed in treated prostatic adenocarcinoma include loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. Involutional changes may be so dramatic that pathologists unaware of these changes will have difficulty in identifying residual disease. Similar changes may be seen in metastatic sites. Electron microscopy of treated tumors suggest that involution is due to programmed cell death (apoptosis). High grade prostatic intraepithelial neoplasia is present less frequently and usually only focally. Treated carcinoma exhibits a paradoxical high Gleason score but its proliferation rate and degree of aneuploidy is less than grade-matched, untreated tumors. Thus, grading of pretreated adenocarcinoma by conventional methods may be misleading and should be avoided. Treatment-related changes are also present in benign prostatic tissue and these include glandular atrophy, basal cell prominence and hyperplasia, and stromal hypercellularity. Several studies suggest pathologic downstaging of the tumor, but it remains unclear whether this finding will result in increased local control.