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.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: O A
authors.initials: OA
authors.lastname: Armas
authors.forename: A G
authors.initials: AG
authors.lastname: Aprikian
authors.forename: J
authors.initials: J
authors.lastname: Melamed
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: D W
authors.initials: DW
authors.lastname: Cohen
authors.forename: R
authors.initials: R
authors.lastname: Erlandson
authors.forename: W R
authors.initials: WR
authors.lastname: Fair
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery / Q000648:ultrastructure; D002455:Cell Division; D003131:Combined Modality Therapy; D004171:Diploidy; D005485:Flutamide / Q000627:therapeutic use*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery / Q000648:ultrastructure
chemical_list: D017273:Goserelin; D005485:Flutamide; D017430:Prostate-Specific Antigen