Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Prostatic Neoplasms

Weight Loss

Obesity

Body Weight

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Body Weight Changes

Hypoglycemic Agents

All Drugs and Chemicals

Insulin

Insulin, Globin Zinc

Mitogens

Subjects undergo a weight loss intervention prior to radical prostatectomy. The intervention includes weekly visits with the dietician, DEXA scanning, blood draws, and anthropometrics.

These subjects do not undergo a weight loss intervention prior to radical prostatectomy. This group does undergo DEXA scanning, blood draws, and anthropometrics prior to radical prostatectomy.

No Weight Loss Group

William Aronson, MD

The purpose of this study is to determine if weight loss prior to radical prostatectomy effects chemical substances in the blood stream and prostate tissue that may affect prostate cancer development and progression.

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.

Effect of Weight Loss on Prostate Cancer Pathology

The primary objective is to compare the mean apoptotic index in the radical prostatectomy malignant epithelium between the Weight Loss Group and the Control Group-No Weight Loss. The apoptotic index will be measured in the malignant epithelium with the highest Gleason grade. TUNEL staining was used to identify these apoptotic cells and measure the apoptotic index, which is the percent of cells stained from the sample.

The proliferative index in prostate cancer epithelium obtained from the radical prostatectomy specimen. This index was procured by staining the Ki67 protein to measure cell proliferation. (Note: Ki67 is a common indicator of cell proliferation.)

This outcome is the measure of the hormone insulin-like growth factor 1 at baseline vs. post-intervention. We measured and compared the concentration (ng/mL) of this hormone.

This outcome is the measure of the protein, insulin-like growth factor binding protein 1, at baseline vs. post-intervention. We measured and compared the concentration (ng/mL) of this protein.

The BRDU assay measures proliferation of cultured cells such as LNCaP. We expose the cells to the patient blood and see if it inhibits prostate cancer cell growth ex vivo. We use optical density (a measure of the amount of light able to pass through the specimen) to indicate the concentration of cell proliferation.

This change in body weight is observed by DEXA, a scanner that measures total body composition.

This change in percent body fat is observed by DEXA, a scanner that measures total body composition.

VA Office of Research and Development

Weight Loss Group

Weight Loss: Subjects undergo a weight loss intervention prior to radical prostatectomy. The intervention includes weekly visits with the dietician, DEXA scanning, blood draws, and anthropometrics.

Arm 1: Weight Loss

No Weight Loss Group

No Weight Loss Group: These subjects do not undergo a weight loss intervention prior to radical prostatectomy. This group does undergo DEXA scanning, blood draws, and anthropometrics prior to radical prostatectomy.

Arm 2: No Weight Loss

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Apoptotic Index of the Highest Gleason Grade Malignant Epithelium in the Radical Prostatectomy Specimen Obtained After 8-weeks of the Dietary Intervention

Spots Global Cancer Trial Database for no weight loss group