Clinical Progression to Castration-Recurrent Prostate Cancer
Since Huggins and Hodges proved unequivocally that prostate cancer (CaP) regresses in the castrate state, androgen deprivation therapy (ADT) has been the cornerstone of treatment for advanced CaP (Huggins and Hodges 1941). This treatment strategy has taken many forms. Bilateral orchiectomy reliably diminishes androgen production and was the mainstay of treatment in the 1940s. In 1941, Huggins and Hodges published their seminal work showing that therapy with estrogen, in the form of diethylstilbestrol (DES), was as effective as orchiectomy (Huggins and Hodges 1941). Chemical castration via DES was widely used until the mid-1960s, when the estrogen formulation was directly compared to other strategies, including bilateral orchiectomy. DES was associated with an improved cancer-related mortality but worse overall survival, due primarily to increased cardiovascular side effects (The Veterans Administration Co-operative Urological Research Group 1967). Despite attempts to find a less toxic but effective dose, DES fell out of favor as an alternative to orchiectomy. In the 1980s, long-acting, synthetic luteinizing hormone-releasing hormone (LHRH) agonists were developed (Tolis et al. 1982). These agents have emerged as the predominant method for achieving castrate levels of androgen.
ADT is highly effective, capable of inducing regression of disease in over 90% of CaP patients (Prostate Cancer Trialists’ Collaborative Group 2000; The Medical Research Council Prostate Cancer Working Party Investigators Group 1997). However, ADT is rarely curative. While the time in remission can vary markedly between patients, CaP invariably becomes refractory to surgical or chemical castration. This chapter will examine clinical progression from androgen dependence to androgen independence, focusing on the clinical factors associated with the emergence of resistance, and the natural history of and treatment strategies for castration-resistant prostate cancer (CRPC).
KeywordsAndrogen Deprivation Therapy LHRH Agonist Bilateral Orchiectomy Chemical Castration Adjuvant Androgen Deprivation Therapy
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