Dec 22 2003. Obese men with prostate cancer are more likely to have aggressive tumors and to experience cancer recurrence after surgery compared to men of normal weight or those who are overweight but not obese, according to two new studies.

Although more research is needed, the findings suggest that men may be able to modify their risk of aggressive prostate cancer by maintaining a healthy weight. The results of both studies were reported December 22 online in the Journal of Clinical Oncology (JCO).

"The primary role of obesity in prostate cancer is still unclear, but it appears to induce the development of more aggressive tumors," said Christopher L. Amling, MD, of the Naval Medical Center's Department of Urology in San Diego and lead author of one of the studies. "I would advise patients to maintain a normal body weight to limit the possibility that they would develop clinically significant, more aggressive prostate tumors."

Both studies examined the relationship between obesity and prostate cancer recurrence in large samples of men with localized prostate cancer who had undergone surgery to remove the prostate - a procedure called radical prostatectomy.

While obesity rates in the general adult population are similar between African-American and Caucasian men, both studies found that obese patients in the study groups were more likely to be African American. This finding may help explain why African-American men with prostate cancer generally have more aggressive tumors and worse outcomes compared to Caucasians.

"We suspect that worse outcomes among African-American men with prostate cancer are related to obesity rather than race. If we can target obesity in the African-American community, we may be able to reduce the burden of prostate cancer among black men," explained lead author of the second study, Stephen J. Freedland, MD of the multi-institution Shared Equal Access Regional Cancer Hospital (SEARCH) Database and currently at the James Buchanan Brady Urological Institute at the Johns Hopkins University School of Medicine.

While other studies have indicated that obesity influences cancer recurrence for women diagnosed with breast cancer, the current studies are the first to investigate the relationship between obesity and prostate cancer recurrence after surgery.

Dr. Amling's study involved 3,162 prostate cancer patients, including 19% who were obese. Obesity was defined as a body mass index of 30 kg/m2 or higher - the equivalent of a 5 foot, 10 inch man weighing 210 pounds or more. In this study, obesity was associated with an elevated Gleason score - a method used to classify the aggressiveness of prostate tumors - and a higher rate of cancer recurrence (determined by elevated PSA levels). African-American men in the study were more likely to be obese (27% vs. 18% of white men), have higher cancer recurrence rates, and more aggressive disease.

Dr. Freedland's study involved 1,106 patients, including 22% who were obese. In this study, mild obesity was also defined as a body mass index of 30 kg/m2 or greater. However, moderate and severe obesity was defined as a body mass index of 35 kg/m2 or greater- equivalent to a 5 foot, 10 inch man weighing 245 pounds or more - and was associated with a higher Gleason score and higher rates of cancer recurrence (determined by rising PSA levels). Men with a BMI of 35 kg/m2 or greater had a 60% risk of cancer recurrence within 3 years, the investigators found. In this study, 31% of African-American men were obese, compared to 21% of Caucasian men.

Both Drs. Amling and Freedland suggest that proteins and hormones stored in body fat - such as leptin and insulin-like growth factor-1 - may promote prostate tumor growth in obese men. Also, obese men typically have lower testosterone levels and higher estrogen levels, which may encourage the growth of cancer. In addition, diets high in fat may promote tumor growth.

An accompanying editorial in the JCO commends the studies for presenting a provocative thesis relating obesity to prostate cancer aggressiveness and outcome.

"In light of the rising incidence of obesity worldwide, identifying obesity as a risk factor for aggressive prostate cancer is important, since it may be one of the few modifiable risk factors for prostate cancer," said Alfred I. Neugut, MD, PhD, Professor of Medicine and Epidemiology, and Head of Cancer Prevention at Columbia University's Herbert Irving Comprehensive Cancer Center and author of the editorial, "The Skinny on Obesity and Prostate Cancer Prognosis."

"The number of prostate cancer survivors is steadily increasing," Dr. Neugut added, "and it will be important to investigate if weight loss and other lifestyle changes can improve prognosis in those already diagnosed with prostate cancer."

"Impact of Obesity on Biochemical Control Following Radical Prostatectomy for Clinically Localized Prostate Cancer." Stephen J. Freedland et al, Johns Hopkins School of Medicine, Baltimore, MD.

"Pathologic Variables and Recurrence Rates As Related to Obesity and Race in Men With Prostate Cancer Undergoing Radical Prostatectomy." Christopher L. Amling et al, Naval Medical Center, Department of Urology, San Diego, CA.

The Journal of Clinical Oncology is the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world's leading professional society representing physicians who treat people with cancer.

Edited by J. Strax, Dec 22, 2003.

Age, Low Calorie Diet, and Rate of Tumor Growth

PSA Rising Dec 24 2003/ Netherlands Organization for Scientifc Research/ A new tumor growth model developed by Dutch scientists reveals that a low-calorie diet delays the growth of a tumor, and thus increases the life expectancy. Furthermore, tumors were found to develop faster in the young (animals or humans) than in the old.

Ingeborg van Leeuwe, a biologist at Vrije University in the Metherlands, has developed this new theory of tumor growth, which views the tumor as an integral part of the body. Existing models regard the tumor as an independent unit, separate from the host in which it grows.

The tumor growth rate was found to be dependent on the age-dependent metabolic rate of the host. The model also established the relationship between the tumour growth process and the host's food intake.

Animals which follow a low-calorie diet have a higher life expectancy upon developing a tumour than animals without any dietary restrictions. The researcher also predicts that tumors generally develop faster in younger than in older hosts. This is because the energy available per cell decreases with age.

Van Leeuwen also developed a model that established the effect of food intake on growth and ageing. The model consists of two modules. The first describes the energy dynamics of an organism and provides equations for the feeding rate, fat content, change in body weight and metabolic rate.

The second module describes the ageing of an organism. This description is based on the theory that ageing is the result of oxidative damage caused by free radicals. The two modules are linked together by the fact that the rate of production of free radicals depends on the metabolic rate, which in turn depends on the energy uptake and body size. In the end, a combination of the two modules results in an equation in which the life expectancy depends on the food consumption and body growth.

For fully-grown animals, the model simplifies to another, already well-known model. This enabled the researcher to ascertain how the parameters of this known model depend on the metabolic rate, feeding behaviour, and body size of the animals.

Edited by J. Strax, Dec 24, 2003.