Arguments against the long-term use of combined androgen blockade

Androgen deprivation therapy is the most effective systemic treatment for advanced prostate cancer. However, as most patients who die from prostate cancer have hormone refractory disease, fine tuning of antiandrogen treatment by combined androgen blockade (CAB) can not be expected to improve survival significantly. Only the South West Oncology Intergroup (SWOG) study 0036 has shown a significant advantage for CAB compared with luteinizing hormone-releasing hormone (LH-RH) agonist alone. However, the results of this study should be interpreted with caution as the patients had to self-administer their treatment by daily injection so compliance may not have been optimal. Also, those receiving LH-RH agonist alone were not covered against disease flare. Indeed, no trial using depot LH-RH agonist with or without flutamide has been able to show a survival benefit. When treatment with LH-RH agonist plus antiandrogen was compared with orchiectomy alone, only the European Organization for Research and Treatment of Cancer (EORTC) study 30,853 showed a significant difference in favour of CAB. However, in this study an increased proportion of patients receiving CAB may have had a more favourable prognosis. Only one study comparing orchiectomy plus antiandrogen with orchiectomy alone has shown an advantage for CAB therapy, and this was only slight. Therefore, as yet there is no justification for long-term use of CAB. However, short-term antiandrogen treatment must be used to prevent disease flare during initiation of LH-RH agonist treatment.