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Intermittent androgen suppression for prostate cancer

Nature Reviews Urology volume 7, pages 552–560 (2010)Cite this article

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Abstract

Although androgen deprivation therapy (ADT) has been a cornerstone of the management of prostate cancer for more than 50 years, controversy remains regarding its optimum application. Intermittent androgen suppression (IAS) has been researched since the mid-1980s as a way of reducing the adverse effects and cost of continuous androgen suppression. With preclinical evidence suggesting a potential benefit in terms of time to androgen independence, IAS has been the focus of a number of clinical phase II and III trials. Overall, these trials suggest that IAS is neither inferior nor superior to continuous androgen suppression, with respect to time to castration resistance and cancer-specific survival, but has significant advantages in terms of adverse effects, quality of life and cost. A number of unresolved questions remain, however, including how to select patients for therapy, the optimum duration of therapy, when to restart therapy after the off cycle, and how to define progression to castration-resistant disease. Landmark randomized clinical trials comparing IAS to continuous androgen suppression are in progress and will hopefully answer many of these questions. In future, the use of second-line drugs in the off-treatment phase holds potential for delaying disease progression in men on IAS. At present, men with advanced disease who are deemed candidates for ADT should be informed of IAS as a treatment option, considered experimental from an informed consent point of view, but promising based on current evidence.

Key Points

  • Androgen deprivation therapy is an effective treatment for prostate cancer, but long-term continuous androgen suppression is associated with significant morbidity, high cost, and potentially an increased risk of mortality

  • Intermittent androgen suppression (IAS) seems to offer equivalent survival outcomes to continuous suppression, with improved quality of life and reduced cost

  • Androgen dependence of prostate cancer can be maintained, although not indefinitely, by cyclic hormone therapy; nadir level of serum PSA is a powerful predictor of time to progression

  • IAS might offer a 'way out' of the immediate versus delayed ADT controversy, by offering the benefits of immediate androgen ablation with reduced treatment-related adverse effects and expense

  • Landmark randomized clinical trials comparing IAS to continuous androgen suppression are in progress and will answer many of the unresolved questions in this field

  • Future improvements to IAS agents and protocols will lengthen the off-treatment time, increase time to castration resistance, and improve prostate-cancer-specific survival

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Figure 1: Model of stem cell composition of the androgen-dependent Shionogi carcinoma.
Figure 2: Effects of intermittent androgen suppression on androgen-dependent carcinoma.
Figure 3: Recovery of testicular function after androgen suppression.

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Laurie Barclay, Medscape, LLC, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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  1. Department of Urologic Sciences and Vancouver Prostate Center, University of British Columbia, 2775 Laurel Street, Vancouver, V5Z1M9, BC, Canada

    Nicholas C. Buchan & S. Larry Goldenberg

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Correspondence to S. Larry Goldenberg.

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Buchan, N., Goldenberg, S. Intermittent androgen suppression for prostate cancer. Nat Rev Urol 7, 552–560 (2010). https://doi.org/10.1038/nrurol.2010.141

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