Prostate cancer is the most common malignancy in men. The median age at diagnosis of prostate cancer is 68 years.1
Prostate cancer does not alter life expectancy for most of these men as the 5-year relative survival for all stages combined is 98.8%.1
Even those who present with metastatic disease have a median survival of approximately 30 months2,3
and a 10-year survival approaching 10%.4
With improvements in cancer-specific survival, treatment-related morbidity has become more relevant to the long-term health of prostate cancer survivors.
Androgens can stimulate prostate cancer growth. Lowering androgen levels with androgen deprivation therapy (ADT) is the primary systemic treatment for prostate cancer. ADT is accomplished by either bilateral orchiectomies or medical castration with a gonadotropin-releasing hormone (GnRH) agonist. ADT achieves objective responses in over 80% of those treated.5,6
Most men are treated with a GnRH agonist rather than bilateral orchiectomies as GnRH agonists are easily administered, reversible, and more acceptable to patients. GnRH agonist use has risen markedly over the last 2 decades across all ages, disease stages and tumor grades.7,8
Currently, more than one-third of the estimated 2 million prostate cancer survivors in the United States are treated with GnRH agonists.9
ADT is the central treatment for metastatic prostate cancer as it improves bone pain, modestly prolongs overall survival and produces some 10-year survivors.10
GnRH agonists have been shown to improve disease-free and overall survival in combination with radiation for locally advanced or high-risk nonmetastatic disease.11,12
Adjuvant therapy with a GnRH agonist also improves survival in men with node-positive disease after radical prostatectomy.13
ADT is also used for settings where evidence of benefit is less clear. PSA monitoring after primary therapy often detects recurrences long before symptoms or imaging would have revealed them. A rising PSA after primary surgery or radiation therapy commonly leads to long-term ADT, although the effects of early ADT for “PSA-only” recurrences on mortality have not been adequately characterized.14
Additionally, some men with localized disease opt for long-term ADT instead of radiation or surgery, a practice that has not been shown to improve survival relative to observation.15
The therapeutic effect of ADT is severe hypogonadism. GnRH agonists lead to a striking reduction in serum testosterone and a number of physiologic changes. Adverse changes in bone mineral density, body composition, lipid profile and insulin sensitivity are among the effects of GnRH agonist therapy. Men receiving GnRH agonists experience elevated risks for fracture,16
diabetes and cardiovascular disease,9
all of which cause substantial morbidity to elderly men at baseline.
With the introduction of PSA screening, fewer than 5% of men have detectable metastases at presentation.17
Earlier diagnosis and more aggressive interventions have increased the burden of treatment for prostate cancer survivors.
Here we provide a focused review of the recently recognized complications of ADT: osteoporosis and fractures, obesity and sarcopenia, insulin resistance and diabetes, and cardiovascular disease. Readers are referred elsewhere for systematic reviews about these and other adverse effects of ADT.18,19
We also provide our recommendations for prevention and treatment of fractures, diabetes and cardiovascular disease in men treated with ADT. Our recommendations, detailed in Table , are adapted from broadly accepted practice guidelines from the National Osteoporosis Foundation (NOF), the American Diabetes Association (ADA), the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the American Heart Association (AHA).
Recommendations for Men Receiving ADT for Prostate Cancer*
Evidence-based guidelines for men on ADT are lacking. This is due in part to the fact that these ADT-specific hazards were identified relatively recently and are still being fully defined. Moreover, few studies of various strategies to screen for and/or manage prostate cancer patients on ADT have been completed to date. Further clinical investigation is needed to better define the most effective strategies to promote health among prostate cancer survivors.