Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which othe r treatments are assessed is surgical castration. It is simple, safe and ef fective, however it is not acceptable to all patients. Medical castration b y means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylst ilboestrol, previously the only non-surgical alternative to orchidectomy, i s no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addi tion of an anti-androgen to medical or surgical castration blocks the effec t of remaining testosterone on prostate cells and is termed combined androg en blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of C AB over castration, whereas others report no significant difference. The au thor favours the view that CAB has an advantage over castration. No study h as reported that CAB is less effective than castration. Of the anti-androge ns which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal ant i-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamid e plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow -up, the groups were equivalent in terms of survival and time to progressio n. However, bicalutamide caused significantly less diarrhoea than flutamide . Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options.