The development of androgen-independent proliferation in prostate cancer is a gradual process and there are a number of steps along the way where the careful use of different modilities of endocrine therapy can cause repeated responses of the malignant cells.
Table 47.1 shows the development of the completely endocrine independent cell occurring in four stages. The hormonenaive patient, who has been diagnosed as suffering from prostate cancer that is no longer to be cured by radical prostatectomy or radiotherapy, will respond to the use of monotherapy with androgen receptor antagonists, either steroidal or non-steroidal, or medical or surgical castration. Within a period of 1.5-3 years the cells will show resistance to this monotherapeutic option and require further hormone treatment. In patients who have received monotherapy with an antiandrogen, there will still be normal levels of testosterone in the blood, but in some instances the levels may be slightly elevated. Withdrawal of the patient's own androgens by means of medical or surgical castration will give rise to further response in approximately half of the patients. In patients who have been medically or surgically castrated, there will be a response in approximately 30% to the administration of an androgen receptor antagonist, which will block the androgens, or androgen precursors, produced by the adrenal glands. At this point, the patient's own testosterone will be at castrate level. Although the tumor is probably now androgen resistant, it will still respond to other endocrine manipulations, such as the administration of corticosteroids or, in the case of MAB, to the withdrawal of an antiandrogen. In addition, at this stage, many patients will respond to estrogens, probably as a result of their cytotoxic effects. Only after further proliferation of the cancer cells is there talk of a truely endocrine-independent
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