Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials

Prostate cancer and the androgen deprivation therapy (ADT) thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25–60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28–1.44). Although the possible relevance of cytokines such as Il-6 and TNF-αto ADT-related diabetes has been suggested, its mechanism is poorly understood.

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Re: Liam Bourke, Stephen Gilbert, Richard Hooper, et al. Lifestyle Changes for Improving Disease-specific Quality of Life in Sedentary Men on Long-term Androgen-Deprivation Therapy for Advanced Prostate Cancer: A Randomised Controlled Trial. Eur Urol 2014;65:865–72;Re: Daniel A. Galvão, Nigel Spry, James Denham, et al. A Multicentre Year-long Randomised Controlled Trial of Exercise Training Targeting Physical Functioning in Men with Prostate Cancer Previously Treated with Androgen Suppression and Radiation from TROG 03.04 RADAR. Eur Urol 2014;65:856–64;Re: Nancy L. Keating, Pang-Hsiang Liu, A. James O’Malley, Stephen J. Freedland, Matthew R. Smith. Androgen-deprivation Therapy and Diabetes Control Among Diabetic Men with Prostate Cancer. Eur Urol 2014;65:816–24;Re: Christina G. Jespersen, Mette Nørgaard, Michael Borre. Androgen-deprivation Therapy in Treatment of Prostate Cancer and Risk of Myocardial Infarction and Stroke: A Nationwide Danish Population-based Cohort Study. Eur Urol 2014;65:704–9

European Urology ◽

10.1016/j.eururo.2014.04.018 ◽

2014 ◽

Vol 66 (3) ◽

pp. e51-e52 ◽

Cited By ~ 5

Author(s):

Sanchia S. Goonewardene ◽

Raj Persad ◽

Annie Young ◽

Adel Makar

Keyword(s):

Prostate Cancer ◽

Randomised Controlled Trial ◽

Androgen Deprivation Therapy ◽

Controlled Trial ◽

Population Based ◽

Androgen Deprivation ◽

Lifestyle Changes ◽

Previously Treated ◽

Randomised Controlled

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Adverse Effects of Androgen Deprivation Therapy: Defining the Problem and Promoting Health Among Men with Prostate Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2010.0014 ◽

2010 ◽

Vol 8 (2) ◽

pp. 211-223 ◽

Cited By ~ 65

Author(s):

Philip J. Saylor ◽

Matthew R. Smith

Keyword(s):

Prostate Cancer ◽

Adverse Effects ◽

Androgen Deprivation Therapy ◽

Locally Advanced ◽

Population Based ◽

Androgen Deprivation ◽

Data Driven ◽

Mineral Density ◽

Clinical Fractures

Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population.

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