Clinical and pathobiological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma Journal Article
| Authors: | Armas, O. A.; Aprikian, A. G.; Melamed, J.; Cordon-Cardo, C.; Cohen, D. W.; Erlandson, R.; Fair, W. R.; Reuter, V. E. |
| Article Title: | Clinical and pathobiological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma |
| Abstract: | Neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancers. We studied 27 clinically localized prostatic carcinomas after 3 months of combined treatment with a luteinizing hormone-releasing hormone agonist, goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic prostatectomy, for changes in the serum prostate- specific antigen (PSA) level, changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy, and proliferative activity. Ten hormonally untreated, grade-matched prostatic adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5 ng/ml, and posttherapy PSA levels were all <4.0 ng/ml, with 18 men having undetectable levels. The mean reduction in prostatic volume following hormonal therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0, and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for proliferating cell nuclear antigen showed >10% nuclear reactivity in 33% of treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of neoadjuvant androgen ablation for localized prostatic carcinoma significantly lowers serum PSA and prostatic volume and produces involutional changes in residual carcinomas that mimic high-grade disease. However, pretreated carcinomas have predominantly a diploid DNA content and low proliferative activity as opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by conventional methods may be misleading. Preoperative total androgen ablation has a profound effect on a subset of prostatic carcinoma cells, possibly by facilitating programmed cell death. |
| Keywords: | immunohistochemistry; clinical article; controlled study; human tissue; clinical feature; clinical trial; histopathology; cancer localization; cancer staging; cell proliferation; prostate specific antigen; controlled clinical trial; phase 2 clinical trial; tumor volume; pelvis lymphadenectomy; cohort analysis; cancer hormone therapy; goserelin; prostatectomy; echography; prostate adenocarcinoma; flutamide; oral drug administration; ploidy; subcutaneous drug administration; human; male; article |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 18 |
| Issue: | 10 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1994-10-01 |
| Start Page: | 979 |
| End Page: | 991 |
| Language: | English |
| DOI: | 10.1097/00000478-199410000-00002 |
| PROVIDER: | scopus |
| PUBMED: | 7522415 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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