Fat Worsens Outcome in Advanced Ovarian Cancer

LOS ANGELES, Aug. 28 -- In advanced ovarian cancer, excess weight shortens the time to recurrence and increases the risk of death, according to researchers here.

Their retrospective chart review of 216 patients "is the first to identify weight as an independent factor in ovarian cancer in disease progression and overall survival," Andrew Li, M.D., of Cedars-Sinai Medical Center here, and colleagues, reported in the Oct. 1 issue of Cancer.

They speculated that some "biologic effect of obesity itself in tumor growth, apoptosis, or chemotherapy resistance pathways" may be responsible for the difference in disease-free and overall survival.

The researchers used medical records of patients undergoing primary cytoreductive surgery for epithelial ovarian cancer at Cedar-Sinai from Jan. 1, 1996, through June 30, 2003. The charts of 216 eligible patients were analyzed for height, weight, age, and comorbidities.

The patients were stratified according to body mass index (BMI), defined as weight in kilograms divided by height in meters squared. Of the total:

• 8% were underweight (BMI less than 18.5).
• 50% were at an ideal weight (BMI at least 18.5 but less than 25).
• 25% were overweight (BMI at least 25 but less than 30).
• 16% were obese (BMI at least 30).

The study found that histology varied with BMI, with obese patients significantly more likely to have a mucinous cancer (at P=0.028). Also, there was a trend toward a nonserous histology in obese women, compared with those of ideal body weight, but it did not reach significance.

When all 216 patients were evaluated, there was no significant difference in overall survival between the obese and ideal body weight groups, Dr. Li and colleagues found. The median survival was 62 versus 80 months, at P=0.28.

But a secondary analysis of the 146 patients with Stage III and IV disease who underwent surgical resection to decrease tumor load and chemotherapy did show differences. Specifically:

• Patients with BMI greater than 25 had an average disease-free survival of 17 months, compared with 25 months for those with BMI less than 25. The difference was statistically significant at P=0.04.
• Median progression-free survival fell overall as BMI increased, from 32 months for underweight women to 24 months for ideal weight women, 18 months for overweight women, and 21 months for obese women. The long-rank test for the trend was significant at P=0.02.
• Overall survival also fell overall as BMI increased. The median survival wasn't reached in underweight women, but it was 70 months for ideal weight women, 79 months for overweight women, and 33 months for obese women. The long-rank test for the trend was significant at P=0.02.

Each one-unit increase in BMI:

• Increased the risk of recurrence by 4%, the researchers said. The hazard ratio was 1.042, with a 95% confidence interval from 1.009 to 1.076; P=0.01.
• Increased the risk of death by 5%. The hazard ratio was 1.050, with a 95% confidence interval from 1.005 to 1.097; P=0.03.

"Our study suggests that fat tissue excretes a hormone or protein that causes ovarian cancer cells to grow more aggressively," Dr. Li said. "The next steps will be to examine this relationship more closely, and to determine the exact biological mechanisms that influence tumor growth in ovarian cancer."

The study was limited, the researchers noted, by its small size and retrospective nature, as well as a potential for treatment bias.