New Study Shows Shorter Survival for Thin Patients With Colorectal Cancer

Though having a high body mass index (BMI) is associated with a higher risk for colorectal cancer, patients who are thinner may not do as well after treatment for metastatic colorectal cancer (mCRC). This research was reported at the recent 2015 European Society for Medical Oncology (ESMO) 17th World Congress on Gastrointestinal Cancer.

“Contrary to our hypothesis, patients who had the lowest BMI were at risk for having the shortest survival,” says lead author Yousuf Zafar, associate professor of medicine at Duke Medicine. “In this case, patients with the lowest body weight — people who had metastatic colon cancer and a BMI of less than 25 — were at the highest risk.

"This effect persisted after adjusting for study, age, ECOG performance status, gender, and hypertension. We did not see any relationship between BMI and progression-free survival.”

The results surprised researchers, who expected obese patients to respond more poorly to treatments for stage 4 colorectal cancer due to their increased risk of developing the disease and having it come back. Additionally, there is some evidence that many obese patients also receive less-than-optimal doses of cancer drugs, or have other health problems that complicate recovery.

According to guidelines, a healthy adult’s BMI ranges from 18.5 to 24, whereas a BMI below 18.5 is considered underweight.

Researchers examined data pooled from 6,128 patients in the U.S. and Europe who had previously been untreated for their mCRC and who were included in four different registry studies. Their average BMI at the start of cancer treatment was 25.3, considered slightly overweight, and all patients received bevacizumab with chemotherapy in their treatment.

The study’s primary endpoints were overall survival (OS) and progression-free survival (PFS).

Median BMI for all patients was 25.3 kg/m². BMI was divided into five categories: less than 20 (532 patients); 20-24 (2,328 patients); 25-29 (2,119 patients); 30-35 (821 patients); and at least 35 kg/m² (328 patients). The majority of patients (5,554) had an ECOG performance status of 0 or 1 and the site of the primary tumor was the colon, rectum, rectum and colon, and recto-sigmoid. Nearly all patients (86 percent) had undergone surgical resection.

Although PFS was similar across baseline BMI categories, investigators found a difference in OS. Patients with BMIs less than 25, 25-29, 30-35, and at least 35 kg/m² demonstrated a median PFS of 10.0, 10.6, 10.5, and 10.9 months, respectively. The median OS in the same four respective BMI ranges was 21.1, 23.5, 24.0, and 23.7 months.

“Proportional hazards models confirmed that low BMI was associated with shortened OS after adjusting for potential differences in baseline characteristics,” commented Zafar.

According to a proportional hazard model using BMI as a continuous variable, a BMI increase of 5 kg/m² was associated with a decrease in the risk of death.

“I see this study as hypothesis-generating and a basis for a randomized, controlled study,” said Zafar during a question and answer session.

The role of high BMI has only recently been evaluated in mCRC, revealing obesity as a risk factor for developing colon cancer. Also, patients with BMI at both the lowest (less than 18.5 kg/m²) and highest (at least 35 kg/m²) levels have been shown to be at higher risk for earlier disease recurrence following adjuvant chemotherapy for colon cancer.

“Although high BMI has been associated with increased risk of colorectal cancer, little is known about how BMI impacts outcomes for patients already diagnosed with mCRC,” remarked Zafar.

“It’s possible that the lowest weight patients may receive adequate first-line treatment but then are too sick to receive subsequent lines of therapy. That may be where we can focus more attention on improving their outcomes.”

Zafar Y, Hubbard J, Van Cutsem E, et al. Survival outcomes according to body mass index (BMI): results from a pooled analysis of 5 observational or phase IV studies of bevacizumab in metastatic colorectal cancer (mCRC). Presented at: 17th World Congress on Gastrointestinal Cancer; July 1-4, 2015; Barcelona, Spain. Abstract LBA-01.