Metabolic Effects of Treatment in Intermediate and High-Risk Prostate Cancer

Intermediate and high risk prostate cancer patients generally undergo either watchful waiting, surgery, RT alone or RT in conjunction with androgen deprivation therapy (ADT). Prostate cancer patients who receive upfront ADT exhibit drastic reductions in testosterone, resulting in the loss of a key anabolic signal and ultimately muscle loss and adipose tissue gain. In non-malignant populations, these changes in body composition are associated with the development of insulin resistance and metabolic syndrome. Hypogonadism is also independently predictive of hyperinsulinemia and metabolic syndrome, and may be the consequence of ADT, increased saturated fat intake, inactivity as well as unhealthy changes in body composition during the treatment time-course. However, it is thought that obesity itself is associated with atherogenic profiles, insulin resistance, biochemical failure, increased risk of cancer recurrence and/or metabolic syndrome in prostate cancer. The loss of muscle is largely attributed to reduced anabolic stimulus due to inactivity and reduced androgen hormones from ADT. As skeletal muscle has an important role in glucose disposal, using RT alone does not reduce androgen hormone levels and may maintain muscle mass to prevent the deleterious metabolic effects exhibited with ADT. Thus, different forms of therapy may present with diverse changes in body composition and ultimately metabolic implications. While there are discrepancies in the success of ADT therapy, this form of therapy invariably results in several detrimental metabolic changes that predispose prostate cancer patients and survivors to developing chronic diseases such as diabetes and cardiovascular disease as well as a greater risk of cancer recurrence. In fact, prostate cancer patients who undergo radical prostatectomy and androgen deprivation therapy, not only lose muscle mass while undergoing treatment but also develop a greater risk of mortality from cardiovascular disease as compared to prostate cancer patients receiving other forms of therapy. To date, no studies have examined the metabolic effects that develop with ADT and/or radiation therapy. The results of the proposed study will indicate the potential metabolic changes that develop with therapy. It is important to identify these unhealthy changes early so that specific nutrition and exercise protocols may be used to improve clinical outcomes.