Muscle Loss Is Associated with Overall Survival in Patients with Metastatic Colorectal Cancer Independent of Tumor Mutational Status and Weight Loss

Abstract

Background: Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival.

Materials and methods: We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status.

Results: We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS-mutant, and 14% BRAF-mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p < .001; 12 months hazard ratio, 2.10; p = .031). We found an association of >5% muscle loss with BRAF-mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status.

Conclusion: Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC.

Implications for practice: In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status.

Keywords: Body composition; Colorectal cancer; Outcomes; Sarcopenia; Skeletal muscle; Survival.

Figure 1

Consort diagram. Flow diagram specifying inclusion and exclusion criteria of patients and computed tomography (CT) scans. All time points ± 45 days. Abbreviations: CT, computed tomography; mCRC, metastatic colorectal cancer.

Figure 2

Change in body composition over time is hard to detect with the naked eye. Serial body composition analysis of a 61‐year‐old male patient with metastatic colon cancer. Left column: Serial axial computed tomography images at the level of the third lumbar vertebral body obtained at the time of metastatic disease diagnosis (baseline), and 3‐, 6‐, and 12‐month follow‐up. Right column: Corresponding segmentation of skeletal muscle (red), subcutaneous adipose tissue (green), and visceral adipose tissue (yellow). Twelve months following the diagnosis of metastatic disease, skeletal muscle had decreased by 20% and adipose tissue had reduced by 44% compared with baseline.

Figure 3

Kaplan‐Meier plots for overall survival. (A) Kaplan‐Meier plots depicting the relationship of the combination of dichotomized skeletal muscle loss with weight loss at 3 months. (B) Relationship of the combination of dichotomized skeletal muscle loss at 3 months with tumor mutational status. Both skeletal muscle and weight loss were dichotomized by >5% versus ≤5%). Abbreviation: WT, wild type.