EAU 2018: Complications of Hormonal Treatment in Prostate Cancer

Copenhagen, Denmark (UroToday.com)  Dr. Sommer gave an overview of the complications associated with the treatment for advanced prostate cancer. The first topic discussed was the acute side effects of androgen deprivation therapy (ADT). These include decreased libido, erectile dysfunction, hot flashes, and fatigue. The chronic side effects include anemia, osteoporosis/fractures, obesity, sarcopenia, lipid alterations, insulin resistance and diabetes. ADT is also associated with other problems, including cardiovascular disease, thromboembolism, colorectal cancer, depression, dementia, and renal failure. 

In the largest series assessing the adverse effects of ADT on prostate cancer patients, [1] more than 26000 patients were analyzed, demonstrating an increased rate of osteoporosis, fractures and hospitalizations due to fractures. The most important risk factors for osteoporosis and fractures are age and duration of ADT. Other risk factors include current smoking, use of systemic corticosteroids for over 3 months and excessive alcohol use. 

At the Advanced Prostate Cancer Consensus Conference in 2017, 87% of the experts have stated that there is strong evidence that ADT increases the risk of bone loss and/or fractures. At commencement and during ADT several actions must be performed regarding bone health. These include:

  1. Assessment of history of fractures and risk factors for osteoporosis
  2. Baseline and yearly measurement of bone mass density
  3. Advice to perform regular physical exercise including aerobic and weight bearing exercises, stop smoking and  limit the amount of alcohol consumption
  4. Total daily calcium intake of 1000 mg
  5. Vitamin D3 supplementation according to baseline level
  6. Consider starting a bone health agent if appropriate
Several studies analyzing population level databases (SEER-MEDICARE, Ontario registry, and Veterans administration) have shown a hazards ratio of 1.24-1.44 in favor of developing diabetes among patients on ADT. Additional relevant recommendations regarding commencement and ADT duration include:

  1. Metabolic risk assessment prior to start of ADT -including BMI and waist circumference, blood pressure, fasting blood glucose, HbA1c, and lipid profile
  2. 6 monthly to yearly metabolic assessments
  3. Lifestyle intervention to prevent weight gain
  4. Smoking cessation
  5. Blood pressure < 130/80
  6. Lipid targets according to treatment guidelines
Metformin reduced the incidence of diabetes, hyperinsulinemia and dyslipidemia. It has also been shown to harbor antineoplastic properties and it has been demonstrated to improve survival in men with prostate cancer.

Dr. Sommer continued to discuss the adverse effects of Abiraterone. Its main toxicities include hypertension, edema, hypokalemia, liver toxicity, cardiac toxicity, and associated steroid adverse effects (due to the fact that prednisone is taken together with abiraterone). Therefore, the management of these patients include monitoring f blood pressure, clinical exam and regular liver function tests, and potassium measurements. Furthermore, patients need a cardiac evaluation before starting treatment, and it is important to check drug-drug interactions and make sure patients are not given potassium lowering drugs.

Enzalutamide was the next topic discussed by Dr. Sommer. Its main adverse effects include central nervous side effects (fatigue, loss of motivation, problems with concentration/memory), seizures, falls, and hypertension. Management of these patients include monitoring of blood pressure, checking drug-drug interactions, and making sure they ae not given drugs that could potentially lower the threshold for seizures.

In conclusion, ADT has significant metabolic and skeletal adverse effects. Patients should be informed and proper monitoring should be performed. Abiraterone and enzalutamide have proven efficacy but also have substantial adverse effects. Treatment choice should also be guided by the adverse effects profile.


Presented by: Silke Gillessen, MD, St. Gallen Switzerland

References:
1. Shahinian et al. New Eng J Med 2005

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark
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