Study Finds Shorter Survival for Thin Patients With Colorectal Cancer

Yousuf Zafar, MD

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), according to new research reported at the recent 2015 World Congress on GI Cancer.

“Contrary to our hypothesis, patients who had the lowest BMI were at risk for having the shortest survival,” said lead author Yousuf Zafar, MD, 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 IV 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 6128 patients in the United States 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 (interquartile range [IQR], 22.6-28.7). BMI was divided into five categories: <20 (n = 532); 20 to 24 (n = 2328); 25 to 29 (n = 2119); 30 to 35 (n = 821); and ≥35 kg/m² (328). The majority of patients (n = 5554) 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%) had undergone surgical resection.

Although PFS was similar across baseline BMI categories, investigators found a difference in OS. Patients with BMIs <25, 25 to 29, 30 to 35, and ≥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 (hazard ratio [HR] = 0.911; 95% CI, 0.879-0.944).

For those with a BMI <20 versus <25, the HR was 1.18. For <20 in comparison with >25, the HR was 1.32. In those with a BMI of >25 kg/m², the HR compared with <20 was 1.12. Using BMI as a categorical variable and adjusting for hypertension at baseline showed a similar pattern across the respective categories.

“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 (<18.5 kg/m²) and highest (≥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.