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ADT in Prostate Cancer: Agonists Versus Antagonists

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Androgen deprivation therapy (ADT) continues to be the mainstay for treating advancing prostate cancer. LHRH agonists, which have been used for decades, create a surge in the testosterone (T) level, and following, the hypothalamic pituitary-gonadal axis shuts down, Neal D. Shore, MD, states.

In 2009, the first LHRH antagonist was approved. Unlike agonists, these newer agents have the benefit of not creating a surge in testosterone The clinical endpoint for approval for both drug classes was T level <50. Shore notes that a level of 50 was used primarily because tests at that time were unable to detect levels lower than 50. However, it is now recognized that lower T levels, particularly in patients with castration-resistant prostate cancer, affect survival. Thus, he stresses the importance of checking patients’ T levels.

There is a lack of clear-cut evidence that a particular ADT strategy results in consistently lower T levels. Shore explains that the real question is whether there are other metrics, including follicle-stimulating hormone (FSH), the surge phenomenon, and the continuity of T suppression, which are capable of differentiating between the impact of agonists and that of antagonists. Additionally, researchers are investigating a possible difference in the agents’ risk profiles for cardiovascular events.

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