Lower BMI, Higher Risk of Progression and Death From Colorectal Cancer

Patients with metastatic colorectal cancer and a low BMI were at higher risk for disease progression and death; this risk did not affect those with a high BMI.

Patients with metastatic colorectal cancer and a low body mass index (BMI) were at increased risk for progression of their disease and death, according to data from a pooled analysis of trials looking at first-line treatment. However, no increased risk for death or progression was seen in patients with an elevated BMI.

“By pooling patient-level data from more than 21,000 individuals enrolled worldwide onto recent major randomized trials for front-line treatment, we have shown that BMI is prognostic for OS [overall survival] and PFS [progression-free survival] in this population, but with a shape of the risk curve across the BMI spectrum different than that observed in the adjuvant setting,” wrote Lindsay A. Renfro, PhD, of the Mayo Clinic in Rochester, Minnesota, and colleagues in the Journal of Clinical Oncology. “Specifically, obese patients with stage II or III colon cancer were previously found to be at increased risk for disease recurrence or death; however, in this study, obese patients with metastatic disease were not at increased risk.”

The pooled analysis included data from 21,149 patients who participated in 25 first-line trials of metastatic colorectal cancer conducted between 1997 and 2012 in the ARCAD (Aide et Recherche en Cancérologie Digestive) database. Only trials that included information on PFS and OS were included.

Across the trials, the median OS was 17.9 months and the median PFS was 8.8 months. Patients had a mean BMI of 26 kg/m2. The patients were classified according to their BMI: underweight patients had a BMI of < 18.5 (3.1%); normal weight, 18.5 to less than 25 (42.8%); overweight, 25 to less than 30 (36.3%); and obese, 30 or greater (17.8%).

A higher likelihood for disease progression was associated with lower BMI (P < .001). In addition, a patient’s BMI was prognostic for both OS (P < .001) and PFS (P < .001). According to the researchers, the increased risk persisted until a BMI of about 28 kg/m2.

“Relative to obese patients, patients with a BMI of 18.5 kg/m2 had a 50% increased risk of death (95% confidence interval [CI], 43% to 56%) and a 27% increased risk of progression or death (95% CI, 20% to 34%); greater risk is suggested for patients with a BMI less than 18.5 kg/m2,” the researchers wrote.

This increased risk remained even after the researchers adjusted for a variety of factors, including age, sex, performance status, and previous chemotherapy use.

“The strongly negative prognostic relationship between low BMI and disease progression or death, together with the significant association between low BMI and poor performance status, suggest that patients with advanced colorectal cancer and low BMI are likely cachectic,” the researchers wrote. “Cancer cachexia affects approximately 50% of patients with colon cancer, and across all tumor groups, cachexia is associated with a 20% mortality rate.”

Looking at differences by gender, the data indicated that having a low BMI was associated with poorer OS in men vs women; however, it also showed the reverse to be true. High BMI was associated with improved OS in men compared with women.

Finally, BMI was not a predictor of any treatment effect, with no difference in PFS or OS with targeted vs nontargeted treatment.