Optimising Hormone Therapy in Advanced Disease

Abstract

Although most prostate cancer (PCa) patients nowadays are diagnosed at an early stage of disease, unfortunately still a significant number of patients will develop advanced PCa or will be diagnosed at an advanced (or metastatic) stage of disease. The group of patients showing the highest increase in incidence are those with rising prostate specific antigen (PSA) after radical therapy. In the last quarter of 2004, a Medline search has been performed targeting publications on patients diagnosed with advanced PCa, as well as with PSA relapse after previous radical therapy. This review aims at providing guidance to optimise hormone therapy in those selected groups of patients by addressing three pivotal questions; (i) who should receive hormonal treatment, (ii) what type of hormonal therapy should the patient be offered and (iii) what is the best timing of starting hormonal treatment. In patients relapsing after radical therapy, the PSA doubling time (PSA DT) has become a critical instrument to distinguish patients to have innocuous PSA evolution from patients at high risk for disease progression. A PSA DT of 3 months seems to be the cut-off point for identifying patients at risk. Therefore patients with a PSA DT of less than 3 months should be advised to initiate hormonal therapy. Antiandrogen monotherapy may be considered in this setting as it has been shown to delay progression; however, significant survival data are not yet available. Whether luteinising hormone releasing hormone (LHRH) agonists should be given continuously or intermittently (IHT) remains subject of debate. Surgical castration has been the standard of care in patients diagnosed with advanced PCa. Currently, LHRH agonists have become the preferred way of suppressing testosterone. Combination of an antiandrogen and a LHRH agonist (CAB) shows a modest benefit over LHRH agonist monotherapy. As CAB leads to increased side effects and costs, LHRH agonist monotherapy is preferred in the majority of patients. Conflicting data have been published concerning the optimal timing of LHRH agonist therapy. So it is not clear whether LHRH agonist therapy should be started immediately or deferred until appearance of symptoms. When initiating continuous hormone therapy, patients should be carefully monitored for the risk of long term androgen deprivation (anaemia, osteopenia and osteoporosis).