Newer Developments in the Management of Prostatic Carcinoma*

Estrogenic Management of Benign Prostatism, Including Early and Poor‐risk Cases: 7‐year Experience*

“…Concerning the mode of action of estrogens in the treatment (and possible prophylaxis) of prostatic carcinoma, many of the direct and indirect effects cited under the section on BPH are probably operative. The following observations also are pertinent: Rosenkrantz and associates (145) noted a reduction in both the volume of secretion and the acid phosphatase content of the prostate following administration of two synthetic estratriene compounds and three stilbene derivatives to testosterone‐maintained castrated dogs with prostatic fistulas. Flocks (146) reported a striking localization of stilbestrol diphosphate within prostate cells after intravenous administration. Blennerhassett and Vickery (147b) noted a consistently increased reaction with glucose‐6‐phosphate and isocitric dehydrogenases and triphosphopyridine nucleotide diaphorase in prostatic carcinoma, but a marked focal reduction in such enzyme activity after orchiectomy and estrogenic therapy. The virtual absence of activity in certain areas tended to correspond with the large pale cells (in H and E sections) that characterize estrogen‐responsive cancer. Acevedo and Goldzieher (79) found that treatment of prostatic carcinoma with massive doses of stilbestrol suppressed 17‐β‐ol‐dehydrogenase activity. Slaunwhite and associates (117) suggested the following effect of estrogens in ameliorating prostatic carcinoma: “The elaboration of 17‐β‐ol‐dehydrogenase, an enzyme which reduces androstenedione to testosterone, is under the control of gonadotrophin.…”

“…In view of the evidences that estrogens can profoundly influence the metabolism of prostatic tissue, androgens, acid mucopolysaccharides, acid phosphatase, growth hormone and the adrenocortical hormones, the prevention or regression of early prostatic carcinoma by female sex hormone commands additional study. Rosenkrantz and associates (145) commented: “Acid phosphatase in the prostate may be very important in the metabolism of that organ, and a search for inhibitors of the biosynthetic pathways of prostatic acid phosphatase may be fruitful in an attack on carcinoma of the prostate.” Similarly, Flocks (146) has stated: “Such systemic treatment—stilbestrol diphosphate in large intravenous doses, stilbestrol diphosphate with P 32 intravenously, thio‐ tepa , nitrogen mustard and other alkylating agents—needs further investigation, not only as adjunctive therapy for the disseminated stage of prostatic carcinoma, but also for the earlier, more localized stages.” The following general data also suggest the merit of this perspective: Prostatic carcinoma generally develops in glands that already exhibit BPH (147). The multiple tumor foci in prostatic carcinoma (147) are consistent with the influence of systemic carcinogenic factors. The higher incidence of lung cancer among males has been interpreted (90a) as indicative of a “more protective endocrine environment” in women. Berndt (90b) suggested the therapeutic value of estrogens in men with bronchial carcinoma. In this same context, Oota (148) reported a two‐fold predominance of primary hepatic cancer among males, based on a sex‐corrected distribution for overall autopsies.…”

“…2. Flocks (146) reported a striking localization of stilbestrol diphosphatP within prostate cells after intravenous administration. 3.…”