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.
• 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.