CJK 02. Intermittent androgen suppression therapy

Hormone therapy (HT) is the mainstay medical therapy for men with advanced prostate cancer (PCa) (ie, locally advanced and metastatic) and is also increasingly used at earlier disease stages, although there are no specific recommendations for these patients as of yet. Although men with PCa may benefit from HT, they will also be subjected to the side-effects of treatment. These side-effects may include hot flushes; sexual problems, such as impotence and decreased libido; fatigue; and psychological effects, such as emotional instability, depression, or cognitive dysfunction. It is also becoming increasingly clear that HT induces accelerated bone loss, eventually leading to osteoporosis and, potentially, to fractures as well as to lipid disorders, obesity, loss of muscle mass, and an increased risk of cardiovascular morbidity and mortality. Over the years, intermittent HT (IHT) has garnered interest in the urologic community as a means to minimize the side-effects of HT and to improve the overall quality of life (QOL) of the patient. Additionally, in the early 1990s, preclinical studies showed that androgen replacement restored the apoptotic potential of the androgen-dependent tumour cells that survived HT and delayed the development of androgen independence. Moreover, in IHT tumour models, such as androgen-dependent Shionogi carcinomas in mice and lymph node carcinomas of the prostate in human PCa xenografts, a prolongation of androgen independence of up to three times was also reported. This finding led to the hypothesis that reexposure of PCa cells to androgen would reinduce the androgen-dependent phenotype and that, therefore, IHT could potentially delay the progression to castration-resistant PCa (CRPC). In addition to the reduction of treatment-related sideeffects and the potential delay of progression to CRPC, the benefits of IHT could also include reduced health care costs. Considering these potential benefits, IHT could be a promising alternative to continuous HT; however, questions remain as to whether the current scientific evidence supports the use of IHT and how IHT should be applied in daily clinical practice.