Androgen-Deprivation Therapy

Posted by • May 27th, 2011

In this week’s Case Record of the Massachusetts General Hospital, a 67-year-old man was seen because of an elevated serum level of prostate-specific antigen 18 months after radical prostatectomy and external-beam radiation therapy for prostate cancer. A management decision was made.

ADT, either by means of bilateral orchiectomies or the administration of a gonadotropin-releasing hormone (GnRH) agonist or antagonist, is the mainstay of treatment for metastatic prostate cancer and for the recurrence of high-risk “PSA only” disease.

Clinical Pearls

What are the benefits of ADT for patients with recurrent or metastatic prostate cancer?

ADT is associated with an objective response rate of greater than 80% and a response duration of approximately 2 years. Long-term neoadjuvant treatment with a GnRH agonist improves the rates of disease-free and overall survival in men receiving external-beam radiation therapy for locally advanced or high-risk nonmetastatic prostate cancer. Adjuvant therapy with a GnRH agonist also improves the survival rate in men with node-positive disease after prostatectomy.

When should ADT be initiated?

In a systematic review of immediate ADT versus ADT that was deferred until clinical progression for men with locally advanced or metastatic prostate cancer, early ADT was associated with greater 10-year rates of overall survival. The estimated number needed to treat to prevent one death at 10 years was approximately 25.

Morning Report Questions

Q: What are the adverse effects of androgen-deprivation therapy?

A: ADT has a variety of adverse effects related to hypogonadism, including loss of libido, vasomotor flushing, fatigue, anemia, and osteoporosis. ADT also is associated with a variety of adverse metabolic effects. ADT decreases muscle mass (by approximately 3% during the first year of treatment) and increases fat mass (by approximately 10% during the first year of treatment). ADT increases fasting plasma insulin levels and decreases insulin sensitivity. ADT also increases the levels of serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Consistent with these adverse metabolic effects, ADT has been linked to increased risks of diabetes and cardiovascular disease.

Q: Which patients receiving ADT should receive antiresorptive therapy?

A: In patients with T scores above −2.5 and no history of osteoporotic fractures, many experts would recommend treatment with calcium and vitamin D and then assess the fracture risk with the Fracture Risk Assessment Tool (FRAX) to decide whether to add an antiresorptive agent. Most current guidelines recommend antiresorptive therapy if the 10-year risks for major osteoporotic fracture and hip fracture exceed 20% and 3%, respectively.

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