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Secondary endocrine therapies for castration resistant prostate cancer

Nancy A Dawson, MD
Section Editors
Nicholas Vogelzang, MD
W Robert Lee, MD, MS, MEd
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD


Androgen deprivation therapy (ADT) is generally the initial treatment for men with advanced prostate cancer, either alone or in combination with chemotherapy. Standard approaches to ADT include orchiectomy, a gonadotropin releasing hormone (GnRH) agonist, or a combination of a GnRH agonist plus an antiandrogen (combined androgen blockade). Despite initial response rates of 80 to 90 percent, nearly all men eventually develop castration-resistant disease. Clinical trials have shown that a number of contemporary systemic therapies can significantly increase overall survival as treatment for castration-resistant prostate cancer in men with castration-resistant disease (table 1).

Several alternative endocrine approaches (other antiandrogens, antiandrogen withdrawal, ketoconazole, glucocorticoids, megestrol acetate, estrogens) have not been demonstrated to improve survival. However, these approaches may induce clinical responses or stable disease. Secondary endocrine therapies are often used sequentially and may be useful in postponing interventions such as chemotherapy with more severe toxicity or when no other effective options are available. These approaches are discussed in this topic.

An overview of the management of advanced prostate cancer is presented separately. (See "Overview of the treatment of disseminated prostate cancer".)


Androgen deprivation therapy (ADT) is generally continued in conjunction with secondary therapies after progression on the initial ADT regimen [1,2]. Androgenic steroids are growth factors for prostate cancer [3]. When disease progresses, discontinuation of gonadotropin releasing hormone (GnRH) agonist therapy can result in an increase in serum testosterone and thus contribute to progressive disease.

There are no randomized trials that directly address the utility of continued ADT in men with castration-resistant prostate cancer. However, a multivariate analysis of 341 patients with castration-resistant prostate cancer who were treated in four clinical trials suggested that continued testicular androgen suppression was associated with a median survival benefit of two to six months [4].


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Literature review current through: May 2017. | This topic last updated: Nov 02, 2016.
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