Neoadjuvant hormonal manipulation: A strategy for chemoprevention trials
Disease Models, Animal
Fragile X Syndrome
Androgen ablation using hormonal manipulation is used extensively in metastatic prostate cancer; however, its use in localized disease combined with surgical extirpation of the gland has not been thoroughly and systematically investigated. The rationale for neoadjuvant therapy stems from the demonstrated effectiveness of androgen ablative therapy in metastatic disease and the high rate of “positive” surgical margins, especially in patients with Stage B2 disease. In addition, the essentially anecdotal clinical report of Scott and Boyd , using endocrine therapy plus radical prostatectomy in patients with Stage C disease, gives 15 years survival results comparable to those obtained by Jewett  in Stage 1 patients treated by radical prostatectomy. Finally, experimental observations in the androgen‐sensitive mammary tumor (Shionogi) lend support to the concept of neoadjuvant hormonal manipulation. A pilot study of neoadjuvant endocrine therapy in 55 patients treated at Memorial Sloan‐Kettering Cancer Center with 3 months of diethylstilbestrol (DES) (3 mg/day) prior to radical prostatectomy indicates marked reductions in the prostate‐specific antigen (PSA), although persistent evidence of adverse local tumor features was common. Some patients, however, exhibited evidence of significant downstaging. Whether or not any alternation in disease progression will accrue from demonstrated local downstaging is, of course, uncertain. However, clinical and laboratory effects of such treatment may provide a means for correlation with subsequent tumor behavior, and may prove useful in treatment decisions. Additionally, a decrease in the number of foci of grade 3 prostatic intraepithelial neoplasia (PIN‐3) was noted in a small number of patients. The effects of hormonal and chemical agents on microfocal “early” prostatic cancer and PIN can be readily evaluated by comparing biopsies obtained before the initiation of such therapy with the effects noted in the radical prostatectomy specimen. Thus, potentially useful agents can be readily evaluated in such a neoadjuvant trial and serve as a means of developing potential chemopreventive strategies. © 1992 Wiley‐Liss, Inc. Copyright © 1992 Wiley‐Liss, Inc.
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