Reducing a weighty prostate-cancer prognosis

Obese men who are diagnosed with prostate cancer have more than two-and-a-half times the risk of dying from the disease as compared to men of normal weight at the time of diagnosis, according to researchers in the Public Health Sciences Division. The study by senior author Dr. Alan Kristal and colleagues appeared in the March 15 edition of the journal Cancer.

"I was very surprised by the results," said Kristal, associate head of the Cancer Prevention Program. "We found the prostate-cancer-specific mortality risk associated with obesity was similar regardless of treatment, disease grade or disease stage at the time of diagnosis."

"If a man is obese at the time of diagnosis, he faces a 2.6-times greater risk of dying as compared to a normal-weight man with the same diagnostic profile, regardless of whether he has a radical prostatectomy or radiation therapy, whether or not he gets androgen-deprivation therapy, whether he has low- or high-grade disease and whether he has localized, regional or distant disease," Kristal said, referring to the degree of cancer spread.

The researchers also found that obese men diagnosed with local or regional disease — that is, disease that is confined to the prostate or has spread into surrounding tissue — face a 3.6-times increased risk of cancer spreading into distant organs, or metastasis, as compared to prostate-cancer patients of normal weight. The association of obesity with disease progression was strongest among men with regional-stage disease at diagnosis, whose cancer had already spread beyond the prostate, as compared to men with early, localized disease.

The inflammation factor

The mechanisms behind the link between obesity, prostate-cancer metastasis and death are believed to involve both steroid hormones and inflammation. "We are now beginning to appreciate that obesity is a massive inflammatory condition, and obesity also increases levels of serum estrogens and growth factors that can promote cancer growth," Kristal said.

For the study, Kristal, first author Dr. Zhihong Gong, a postdoctoral research fellow in the Cancer Prevention Program, and colleagues at the Hutchinson Center and the University of Washington followed 752 recently diagnosed middle-aged, Seattle-area prostate-cancer patients for about 10 years. Body-mass index, or BMI, in the year before diagnosis was determined during an initial interview. Seventeen percent of the participants were classified as obese, with a BMI of 30 or more. Of the men studied, 50 died of prostate cancer and 64 died of other causes.

Only one other study has examined obesity and prostate-cancer outcome; this study reported no association between the two, but the study was limited to men at one hospital, all of whom received radical prostatectomy.

Kristal's study is the first long-term, population-based study of prostate-cancer patients who have undergone a variety of treatments. A strength of the study is that it used metastasis and mortality as an endpoint versus biochemical recurrence (the presence of circulating prostate-specific antigen, or PSA, in the blood after treatment, a biomarker of limited value in predicting death from prostate cancer).

"I think this study represents the first good piece of evidence that losing weight may in fact reduce the risk of dying of prostate cancer," Kristal said. "Although one would need a randomized clinical trial to definitively determine whether weight loss could be an effective complimentary treatment for obese men diagnosed with prostate cancer, these results offer yet another good reason for men to achieve and maintain a healthy weight," he said.

Co-author Dr. Janet Stanford, of PHS, provided data for the study. Funding came from the National Institutes of Health, the National Cancer Institute and the Hutchinson Center.