Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy

Abstract

Background: Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear.

Methods: The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2-sided.

Results: During a median follow-up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal-weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (Pinteraction = .0129). Men with class 2 and 3 obesity (BMI ≥ 35.0 kg/m(2) ) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; P = .0297) compared with normal-weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09-1.28; P < .0001) that was more significant among men (HR, 1.31; 95% CI, 1.15-1.50; P < .0001) than among women (HR, 1.11; 95% CI, 1.01-1.23; P = .0362; Pinteraction = .0340). BMI was not predictive of a benefit from adjuvant treatment.

Conclusions: Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials.

Figure 1

Kaplan-Meier plots showing the association of BMI category with time-to-recurrence (TTR) and overall survival (OS) in men (A, C) and women (B, D) with resected, stage II and III colon cancers who participated in adjuvant chemotherapy trials.

Figure 2

BMI is modeled using restricted cubic splines in all patients (A) and by patient sex (B) for overall survival (OS). Hazard ratios (HRs) for OS are shown for BMI values (range 15 to 40 relative to no effect). Plots used 4 knots that were all statistically significant (p< 0.025). Instead of the y axis being shown in log scale, transformation to a HR scale was performed to enhance interpretability.