What is the role of ADT in the treatment of metastatic and advanced prostate cancer?

Updated: Dec 29, 2020
  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Considered to be the primary approach in the treatment of symptomatic metastatic prostate cancer, androgen-deprivation therapy (ADT) has been found to be palliative, not curative. Although this therapy can slightly improve the likelihood of survival, most men progress to hormone-refractory prostate cancer, also termed androgen-independent cancer. These patients have disease progression despite castration levels of ADT.

Combined androgen blockade (CAB) recognizes the 10% contribution of adrenal androgens to the total body testosterone. A gonadotropin-releasing hormone (GnRH) antagonist with a nonsteroidal antiandrogen is used concurrently for what was thought to be complete ADT. However, multiple randomized trials have shown conflicting findings regarding significant improvement in survival.

Labrie and colleagues described the concept of CAB, in which luteinizing hormone-releasing hormone (LHRH) accomplished medical castration and antiandrogens achieved peripheral blockade. Initially, the investigators reported improved response and survival rates. [26] Additional studies supported these findings.

However, a meta-analysis by the Prostate Cancer Trialists' Collaborative Group, which included 22 trials with a total of 5710 patients with advanced prostate cancer, found no statistically significant survival advantage with CAB. Medical castration and bilateral orchiectomy were included. The overall mortality rate was 56.3% in patients receiving CAB versus 58.4% in patients receiving medical or surgical castration alone. Estimated 5-year survival rates were 26.2% with CAB and 22.8% with castration alone. [27, 28] The current American Society of Clinical Oncology (ASCO) guidelines recommend castration alone with either an orchiectomy or GnRH agonist.

In May 2010, the US Food and Drug Administration (FDA) stated that a preliminary and ongoing analysis found that men receiving gonadotropin-releasing hormone (GnRH) agonists were at a small, increased risk for diabetes, heart attack, stroke, and sudden death. On October 20, 2010, the FDA announced that prescribing information for GnRH agonists would include new warnings describing the increased risk for heart disease and diabetes. [29]

The following GnRH agonists are approved in the United States:


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