Obesity is Risk Factor for Aggressive Prostate Cancer

Obesity appears to increase the risk of prostate cancer, particularly aggressive disease, and may make it harder to find, researchers say.

Smaller prostates also increase the risk of aggressive disease, they say.

Both findings are being presented at the annual meeting of the American Urological Association May 21-26 in San Antonio.

The obesity study examined the association between body mass index – weight to height ratio – and prostate cancer in 787 men undergoing biopsy due to an elevated tumor marker in the blood or an abnormal physical exam at a Veterans Affairs hospital in California between 1998 and 2002.

It indicated that obesity increases the risk of prostate cancer, particularly in young men, as well as the risk of aggressive disease in all men.

“The exact relationship between obesity and prostate cancer is still very much a point of controversy and debate in urology,” says Dr. Martha K. Terris, urologist at the Veterans Affairs Medical Center in Augusta and the Medical College of Georgia.

“One consensus that seems to be evolving is that obese men have an increased risk of more aggressive, and therefore potentially more deadly, disease,” she says. “The take-home message for men and for all of us really is that we should try to maintain a healthy weight for a variety of health reasons.”

Obesity may literally be a deterrent to finding prostate cancer because it makes digital rectal exams, a major screening tool, more difficult, says Dr. Terris. Also, in men and women alike, fat makes estrogen-like compounds, which lowers circulating levels of prostate specific antigen, or PSA, a marker for prostate cancer. If PSA levels are lower due to hormone changes from obesity, the prostate cancer is less likely to be detected at an early stage.

Hormone changes observed with obesity also cause decreased levels of the male hormone testosterone. Since testosterone feeds prostate cancer, obesity could, in theory at least, reduce the risk of prostate cancer. This reasoning remains controversial, however since the current study and others suggest that obese men actually may be at increased risk for prostate cancer. However, researchers are more convinced of the link between obesity and aggressive prostate cancers that do not rely on testosterone to grow.

“Hormone balance has potent effects on the prostate and prostate cancer,” Dr. Terris says. “Most prostate cancer researchers have accepted the suggestion that higher estrogen and lower testosterone suppress prostate cancer growth with the exception of those cancers that are not sensitive to testosterone. However, when we adjusted for age in this study, we didn’t necessarily find less cancer. We did find that men with a higher body mass index did indeed have higher-grade, more aggressive-appearing cancer.”

A study published in February 2004 in Journal of Clinical Oncology also found higher rates of aggressive cancer in obese men as well as higher recurrence rates after surgery. That study, for which Dr. Terris was the senior author, looked at 1,106 men who had cancerous prostate glands removed at Veterans Affairs Medical Centers in Augusta, West Los Angeles, San Francisco and Palo Alto, Calif., as well as the San Diego Naval Medical Center from 1988 to 2002. The hospitals comprise the Shared Equal Access Research Cancer Hospital, or SEARCH, Database, so named because access is based on military service requirements rather than paying status.

The 1,106 men included 330 of normal weight, 528 considered overweight and 214 mildly, moderately or severely obese. “Obesity was associated with higher-grade tumors, increased risk of positive surgical margins, and higher biochemical failure rates among men with clinically localized prostate cancer treated with (radical prostatectomy),” the study authors concluded. “Severely and moderately obese patients were at higher risk of failure than mildly obese patients,” with risks two to three times that of slimmer patients.

The new study exploring the relationship between the size of the prostate gland and severity of disease also looked at patients in the SEARCH Database.

“Men with smaller prostates tend to have smaller cancers than men with larger prostates. But this is not as good as it sounds,” says Dr. Terris, a Georgia Cancer Coalition Distinguished Scholar. “If you have a large prostate, cancer can grow to a fairly large size before it outgrows the surrounding prostate and spreads out into other areas of the body. However, if the prostate containing the cancer is small, the cancer does not have to grow very much before it is big enough to spread outside the gland.” But this story gets more complicated. Men with larger prostates naturally have higher PSA levels, which means they may be more closely followed so their cancers are caught earlier. Also, the size of the prostate is linked to genetic and testosterone levels.

“Similar to the findings in obese men with prostate cancer, the explanation may be differences in hormone levels,” says Dr. Terris. “If you have estrogen or less testosterone in your system, your prostate will not be as large as a man with a high testosterone because these hormone affect both benign prostate growth and cancer. As a result, the same hormone balance that result in a small prostate gives hormone insensitive tumors more chance to grow.”

Dr. Terris conducted the studies with colleagues at Johns Hopkins University, University of California Los Angeles, University of California San Francisco, and Stanford University.