Skeletal muscle alterations and functional repercussions in patients with colorectal cancer-associated cachexia

Cancer cachexia causes skeletal muscle wasting and metabolic dysfunction, worsening clinical outcomes in colorectal cancer (CRC). This study examines microscopic and macroscopic skeletal muscle fiber characteristics, and muscle volume in patients with CRC-associated cachexia and without cachexia compared with healthy controls (HCs), and explores how these factors relate to physical performance. In total, 12 patients with CRC-associated cachexia, 25 CRC patients without cachexia, and 25 HCs were included. Cachexia was determined by weight loss and Cachexia Staging Score. Biopsies from the vastus lateralis and erector spinae muscles were analyzed using immunohistochemistry for muscle fiber type cross-sectional area (CSA) and distribution, myonuclear content, and capillary density. Muscle volume was assessed using three-dimensional ultrasound, and CSA and density by computerized tomography scans. Physical function was evaluated with the Short Physical Performance Battery test, handgrip strength, and the Physical Activity Scale for Individuals with Physical Disabilities. Quality of life was assessed using the 36-item Short Form Survey. Patients with CRC-associated cachexia showed reduced type II muscle fiber CSA in the vastus lateralis compared with HCs and CRC patients without cachexia. CRC Patients without cachexia exhibited a slow-to-fast muscle fiber shift compared with HCs. Myonuclear content was lower in both cancer groups. Muscle volume and density were reduced in patients with CRC-associated cachexia. Positive correlations were found between microscopic and macroscopic skeletal muscle characteristics, muscle strength, physical performance, and quality of life, respectively. CRC Patients, especially those with cachexia, showed type II muscle fiber atrophy, reduced myonuclear content, and impaired physical function, emphasizing the need for targeted prehabilitation interventions.NEW & NOTEWORTHY This study reveals skeletal muscle alterations in colorectal cancer patients with cachexia, at microscopic (fiber-type specific atrophy, myonuclear content, and capillarization) and macroscopic levels (muscle volume and quality). These alterations were associated with clinically important measures of physical functioning and quality of life. Collectively, these findings establish clinically relevant links between structural muscle alterations and physical outcomes, highlighting the potential value of targeted (p)rehabilitation interventions in these patient populations.