Obesity Doubles Odds of Prostate Cancer Mortality

SEATTLE, March 15 -- Obese men diagnosed with prostate cancer in middle age are at a 2.6-fold higher risk of dying from the disease than are patients of normal weight, according to a case-control study.

Surprisingly, the increased prostate-cancer-specific mortality risk was independent of treatment and key prognostic factors at diagnosis, including disease grade and stage, reported Alan R. Kristal, Dr.P.H., of the Fred Hutchinson Cancer Research Center here, and colleagues, in the March 15 issue of Cancer.

Epidemiology data has consistently indicated a modest increase in prostate cancer mortality among men with a body mass index (BMI) of 30 kg/m² or greater. However, it was unclear whether the effect was due to poor prognostic factors or an effect on progression after treatment.

So, the researchers looked at 752 men ages 40 to 64 with newly diagnosed, histologically confirmed prostate cancer in the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The men reported their pre-diagnosis height and weight in a baseline interview and were followed through the registry for an average of 9.5 years.

The mean BMI was 26.7 kg/m², and 17.0% of the men were obese. About a quarter had regional- or distant-stage prostate cancer at diagnosis (27%), and 14% had Gleason scores of 7 or higher. Most underwent radical prostatectomy as the primary treatment (63%).

During follow-up, 50 men died of prostate cancer, 64 died of other causes, and 36 developed metastases.

The researchers found that obesity at diagnosis significantly increased risk of prostate-cancer-specific mortality (hazard ratio 2.64, 95% confidence interval 1.18 to 5.92, P=0.03 for trend) after controlling for age, race, smoking status, and clinical prognostic factors at baseline. Mortality from other causes was not linked to BMI (P=0.40).

The prostate-cancer-specific mortality rates were:

• 6.5 per 1,000 person-years for normal or underweight men (BMI less than 25 kg/m²).
• 5.4 per 1,000 person-years for overweight men (BMI 25 to 29.9 kg/m²).
• 13.0 per 1,000 person-years for obese men.

When the researchers stratified mortality by BMI categories, the adjusted findings were:

• No significant associations between obesity and Gleason score (P=0.72 for interaction), cancer stage (P=0.78 for interaction), or serum prostate specific antigen level at diagnosis (P=0.11).
• No significant trend for higher mortality with higher BMI whether the primary treatment was radical prostatectomy (P=0.26 for trend) or androgen-deprivation therapy only (P=0.07 for trend).
• No significant association between mortality and androgen-deprivation therapy use (P=0.32 for interaction) though there was a suggestion that the risk was higher among those that did not receive it (HR 15.92, 95% CI 1.37 to 85.18).

Obesity also significantly increased the risk of metastasis for men diagnosed with local- or regional-stage disease (HR 3.61, 95% CI 1.73 to 7.51, P=0.0006 for trend). This finding did not vary significantly across BMI strata with Gleason score, cancer stage, or primary treatment.

Mechanisms by which obesity could affect cancer outcomes may include altered steroid hormone concentrations, high levels of leptin and other adipokines, and inflammation, Dr. Kristal and colleagues suggested.

They said their findings were unlikely to be biased by the effects of treatment or diagnosis on weight since men reported their pre-diagnosis weight and androgen-deprivation treatment showed no interaction with reported BMI.

However, they noted that such self-reports may have introduced error.

While it is unknown whether weight reduction post-diagnosis could affect prostate cancer outcomes, the researchers said the study suggests that this avenue should be studied.

"Although a randomized clinical trial would be needed to definitively determine whether weight reduction would be an effective adjunct treatment for men diagnosed with prostate cancer," they wrote, "these results provide yet one more important reason for men to adopt healthful patterns of diet and physical activity to achieve and maintain a normal weight."