Low Muscle Density Is Associated with Morbidity and Systemic Inflammation in Colorectal Cancer, Independent of Tumor Factors.

BACKGROUND

Low skeletal muscle index (SMI) and skeletal muscle density (SMD) are associated with poor postoperative outcomes in colorectal cancer. However, standardized diagnostic thresholds remain undefined.

METHODS

In total, 927 patients with stage I to IV colorectal cancer were included. Preoperative computed tomography was used to determine body composition parameters. Optimal stratification was applied to identify the sex-specific and body mass index (BMI)-specific SMD and SMI cutoffs. SMD and SMI were analyzed as continuous variables relative to clinicopathologic features, systemic inflammatory markers, and sex-specific quartiles in survival analyses using Kaplan-Meier and Cox regression methods.

RESULTS

Optimal stratification did not yield reproducible cutoff values for SMI or SMD. In multivariable analysis, low SMD and SMI were associated with female sex, older age, and BMI, whereas tumor-related factors were not associated with either measure. Low SMD was associated with systemic inflammation, including elevated circulating C-reactive protein and interleukin 6 (IL6) levels, whereas low SMI showed only a nominal association with elevated IL6 levels after adjustment. Low SMD independently predicted poorer cancer-specific survival [multivariable hazard ratio (HR) for lowest vs. highest SMD = 4.29; 95% confidence interval (CI), 1.86-9.91; P = 0.001] and overall survival (HR for lowest vs. highest SMD = 3.42; 95% CI, 1.62-7.25; P = 0.003) in women but not in men, whereas SMI was not associated with survival.

CONCLUSIONS

Low SMD is a sex-specific prognostic factor. Incorporating SMD assessment into preoperative risk stratification may enhance individualized management, particularly for female patients.

IMPACT: Survival-based cutoff values for SMD or SMI in colorectal cancer could not be established. Moreover, preoperative body composition reflects patient-related factors rather than tumor-induced changes.