Adiposity and Outcomes of Clinically Localized Prostate Cancer


This study attempts to clarify the mechanistic basis for the association between adiposity and risk factors for prostate cancer-specific morbidity and mortality in men with clinically early-stage prostate cancer. Our overall hypothesis is that excess adiposity alters prostatic exposure to physiologic factors that are influenced by weight status and implicated in prostate cancer progression, and that these changes at the gland level mediate the effect of adiposity on the presentation and course of the disease. Therefore the specific aims of this 5-year study are to:

  1. Conduct a prospective 2-year cohort study of incident cases of clinically localized prostate cancer to examine the association of adiposity with pathologic features at diagnosis and biochemical failure-free survival after radical prostatectomy;
  2. Measure fatty acids, insulin-like growth factor (IGF) axis activity, modulators of inflammation, and sex steroid hormone profiles in prostate tissue and periprostatic fat, and use mediation model analysis to determine which physiologic variables account for the association of adiposity with tumor characteristics and biochemical failure-free survival;
  3. Evaluate the effects of post-treatment changes in adiposity on 2-year risk of biochemical failure.

The cohort will consist of 400 men enrolled in the urology clinics of four medical Chicago-area medical centers who are awaiting radical prostatectomy. Adiposity is quantified at the time of diagnosis and one year after surgery by anthropometry and dual energy x-ray absorptiometry. Pathologic tumor characteristics are determined by a single pathologist, and biochemical outcomes are ascertained using a standard protocol. Potential mediators that are studied include fatty acids, IGF-1 receptor signaling proteins, adipose tissue-derived cytokines, eicosanoids, and metabolites of estrogen and testosterone.

Lifestyle factors that associate with more rapid progression of clinically early-stage prostate cancer are of increasing concern to health care providers and public health professionals. This research identifies some of the biological reasons why obesity associates with more "aggressive" prostate cancer at diagnosis and decreases a patient's chances for cure with surgery. This research also sheds light on ways to prevent cancer recurrence that may involve new or existing medications or lifestyle changes. 

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