Antiandrogen withdrawal syndrome associated with prostate cancer therapies- Incidence and clinical significance

The antiandrogen withdrawal syndrome is a well established phenomenon in pr ostate cancer. It is widely accepted that a subset of patients will benefit from the withdrawal of antiandrogen or steroidal hormone from hormonal the rapy, exhibiting decreasing prostate-specific antigen (PSA) values and clin ical improvement. The pathophysiology of antiandrogen withdrawal syndrome i s not completely understood, although androgen receptor gene mutations seem to be the likely explanation. Currently, it is not possible to identify th e subset of patients whose tumours will respond to antiandrogen or steroid withdrawal. Tumours that will respond may be classified as androgen-indepen dent and hormone-sensitive tumours as opposed to androgen-independent and h ormone-insensitive tumours that do not respond. Patients who respond to ant iandrogen withdrawal experience approximately 6 months with improved qualit y of life; however, it is unknown if this translates into prolonged surviva l. At the very least, antiandrogen withdrawal offers a therapeutic modality that is not associated with adverse effects and improves quality of life e ven if only for a very limited time. Recent reports suggest that adding a secondary hormonal therapy such as ami noglutethimide, ketoconazole or steroidal hormones may enhance the response rate and prolong response time to the antiandrogen withdrawal syndrome. Ho wever, unless there is proof that this secondary hormonal manipulation prol ongs survival, maintenance of quality of lift: is mandatory because of the possible adverse effects from these potent drugs. The fact that about 30% of patients will respond to antiandrogen or steroid withdrawal in hormone refractory prostate cancer must be taken into accoun t in clinical trials of new cytotoxic agents which have been and will be co nducted. Cessation of flutamide for at least 4 weeks and, in the case of bi calutamide, even 8 weeks. is mandatory before antiandrogen withdrawal syndr ome can be excluded aa the cause of decreasing PSA values. The antiandrogen withdrawal syndrome offers another piece of the puzzle of Prostatic carcinoma, but at the same time it demonstrates how different adv anced prostate cancer cells may react to therapeutic strategies and, theref ore, hormone refractory prostate cancer remains a difficult challenge which must be solved in the future.