Advanced prostatic adenocarcinoma: biological aspects and effects of androgen deprivation achieved by castration or agonistic analogues of LHRH.
Twenty-nine patients with advanced prostatic adenocarcinoma were evaluated clinically, biochemically and radiologically and randomly assigned either to orchiectomy or to medical treatment. The latter consisted of the chronic administration of an LHRH agonistic analogue by parenteral and/or intranasal routes. Plasma testosterone levels fell to castrate values and remained so for as long as the follow-up lasted (24 months); estrogen levels fell as well. No change in basal cortisol, thyroxine or prolactin levels was noticed. A decrease in prostate size and improvement in prostatism occurred in all. Bone pain and radiology conventionally or by isotopic scanning, did not parallel the improvement seen in the primary disease locus. Similarly, the changes in alkaline phosphatase were minimal when compared to that of prostatic acid phosphatase. Both enzymes increased prior to or concurrently with relapse of the disease. The longest remission and survival was seen in patients with low enzyme levels, non diffuse bone metastases and high degree of tumor differentiation. Chronic use of agonistic analogues of LHRH induces effective castration in men with prostatic carcinoma and can replace orchiectomy or estrogen administration. The quantitative analysis of androgen receptors (AR) in subcellular fractions of tumor cells; the use of techniques to enhance the number of AR in the cytosol; and the determination of the type II/I regulatory subunit of protein kinase may be used to identify hormone independent clones and spare patients of unnecessary procedures.