Effect of Weight Loss on Prostate Cancer Pathology

Obesity is an epidemic, a major public health concern, and is a significant risk factor for
progression and mortality from prostate cancer. Prior work in the investigators' laboratory
in pre-clinical prostate cancer models and in obese men found that a low fat diet, exercise,
and weight loss resulted in antiproliferative and pro-apoptotic effects on prostate cancer
tissue through mechanisms related to the IGF-axis. The investigators now propose to conduct a
prospective, randomized clinical trial in overweight and obese men with prostate cancer
undergoing radical prostatectomy to evaluate if weight loss prior to radical prostatectomy
results in antiproliferative and pro-apoptotic effects in prostate cancer tissue. The
investigators will accomplish this aim by enrolling overweight and obese men with prostate
cancer scheduled to undergo radical prostatectomy. Following informed consent, men will be
randomized to either immediate radical prostatectomy or to an 8-week weight loss intervention
group that will undergo a diet and exercise weight loss program followed by radical
prostatectomy. Proliferation and apoptosis of prostate cancer cells in the prostatectomy
specimen will be compared between the groups and relative to the baseline prostate needle
biopsy specimens. Further studies will evaluate potential serum surrogate biomarkers that the
investigators developed in the investigators' laboratory (ex-vivo serum bioassays) and serum
and tissue IGF-axis proteins that have previously been related to obesity, weight loss, and
prostate cancer progression. The goal of the investigators' project will be to evaluate the
potential anticancer effects of weight loss on prostate cancer tissue and to identify
surrogate serum biomarkers that reflect antiproliferative and pro-apoptotic tissue effects
and can be applied to future secondary prevention trials in overweight and obese prostate
cancer survivors.

Inclusion Criteria:

- Subject is overweight or obese (BMI > 25 kg/m2)

- Patient with pathologically confirmed adenocarcinoma of the prostate and has elected
to undergo radical prostatectomy

- Willing to delay radical prostatectomy for 5 to 8-weeks if randomized to the weight
loss intervention group.

- Able to adhere to physical activity intervention (able to walk for 30 minutes without
rest)

- Able to come to the VA for weight loss visits during the 5 to 8-wk study

Exclusion Criteria:

- Any one of the following: Gleason grade > 4+4, PSA > 20.

- History of ever receiving androgen deprivation therapy, antiandrogen therapy, or
finasteride

- Prior prostate radiotherapy (external beam or brachytherapy) or prior cryotherapy

- Diagnosis of diabetes mellitus and on insulin**

- Current use of weight loss medications or enrolled in a diet/weight loss program

- Current use of lycopene supplements*** Significant co-morbidities (i.e. cardiac,
pulmonary, liver disease, ongoing alcohol/drug abuse) Cardiac pacemaker