Leonard G. Gomella, MD
Androgen-deprivation therapy (ADT) is a mainstay of treatment for prostate cancer in a number of settings, so managing its side effects is becoming increasingly important for urologists in collaboration with oncologists and primary-care physicians.
The issue is of particular concern due to the availability of newer agents that decrease testosterone levels for longer periods of time, and also with the use of ADT in non-metastatic prostate cancers, which ultimately lengthens the time men spend on antiandrogen drugs, according to Leonard G. Gomella, MD, chairman of the Department of Urology at Thomas Jefferson University Hospital, in Philadelphia.
ADT can involve bilateral orchiectomy or the use of estrogens, luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, antiandrogens, newer agents such as abiraterone, or the secondary administration of ketoconazole, said Gomella, who addressed the topic during the 7th Annual Interdisciplinary Prostate Cancer Congress, held March 15 in New York City. The strategy, he said, is most appropriately used upon diagnosis of metastatic prostate cancer; with radiation in intermediate- to high-risk prostate cancer; to stimulate volume reduction before brachytherapy; and after treatment failure in localized disease, although the timing in that setting is controversial.
With increased use of the strategy have come growing concerns over side effects including hot flashes, loss of libido, fatigue, anemia, muscle loss, osteoporosis, and bone fracture.
Adverse events can also include depression, memory difficulties, and emotionality, as well as metabolic syndrome, which comprises obesity/sarcopenia, diabetes, and cardiovascular disease. While giving ADT on an intermittent schedule can help ease these side effects, the jury is still out on whether that method is as effective in treating prostate cancer as continuous therapy, Gomella said.
He suggested that urologists enlist the help of primary-care physicians in monitoring the possible development of ADT side effects by referring patients to be followed with screenings.
Gomella explained that gonadotropin-releasing hormone (GnRH) agonists increase cholesterol and triglycerides,1
boost obesity,and heighten insulin resistance2
in men with prostate cancer, potentially leading to diabetes mellitus, coronary heart disease, and myocardial infarction.3
To monitor for signs of diabetes, urologists or primary-care physicians should conduct blood screens for glycated hemoglobin, diabetes, and pre-diabetes on these patients at baseline and then yearly, and should promote weight loss and physical activity,4
Tracking potential cardiovascular complications should involve screening for fasting lipoproteins at baseline, 1 year, and then every 5 years, and assigning a target LDL cholesterol level based on major risk factors for coronary heart disease, Gomella said. Prevention in this setting, he said, should focus on the treatment of hypertension, tobacco cessation efforts, the promotion of healthy lifestyle choices, and the use of first-line statins for hyperlipidemia when needed.4
Bone Mineral Density
While a normal man loses 0.5% of his bone density in a year,5
men on ADT lose 4.6% of their bone density in that period,6
a trend that “adds up over the long term and has the potential to cause great morbidity and in fact mortality,” Gomella said. After being on these medications for 10 years, 80% of men have osteoporosis,7
One study found that the likelihood of experiencing a bone fracture between 1 and 5 years after treatment with a GnRH agonist increased 6.8%, to a frequency of 19.4%, in patients with prostate cancer who received ADT as compared to patients with the disease who were not treated with ADT; in the ADT group versus the non-ADT group, 5.2% versus 2.4% of patients experienced fractures that required hospitalization.8
Fractures in areas such as the hip can significantly decrease a patient’s longevity, and men fare much worse in that situation than women do, Gomella noted.9
Monitoring bone mineral density (BMD) remains the gold standard for diagnosing osteoporosis in clinical practice, the doctor said, as it is one of the best ways of determining bone strength and predicts fracture as reliably as blood pressure predicts stroke. A DEXA bone scan T-score of <-2.5 indicates osteoporosis, he said. He added that the World Health Organization has a fracture risk assessment questionnaire that physicians might find helpful.
In general, he said, osteoporosis prevention should start with “the easy stuff” before more complicated interventions are used.
One simple tactic for prevention is the administration of vitamin D, which at 700 to 800 IU per day can lower the risk of bone fracture by 26%, Gomella said.10