Background Current literature is inconsistent in the associations between computed tomography (CT)‐based body composition measures and adverse outcomes in older patients with colorectal cancer (CRC). Moreover, the associations with consecutive treatment modalities have not been studied. This study compared the associations of CT‐based body composition measures with surgery‐ and chemotherapy‐related complications and survival in older patients with CRC. Materials and Methods A retrospective single‐center cohort study was conducted in patients with CRC aged ≥65 years who underwent elective surgery between 2010 and 2014. Gender‐specific standardized scores of preoperative CT‐based skeletal muscle (SM), muscle density, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue, IMAT percentage, SM/VAT, and body mass index (BMI) were tested for their associations with severe postoperative complications, prolonged length of stay (LOS), readmission, and dose‐limiting toxicity using logistic regression and 1‐year and long‐term survival (range 3.7–6.6 years) using Cox regression. Bonferroni correction was applied to account for multiple testing. Results The study population consisted of 378 patients with CRC with a median age of 73.4 (interquartile range 69.5–78.4) years. Severe postoperative complications occurred in 13.0%, and 39.4% of patients died during follow‐up. Dose‐limiting toxicity occurred in 77.4% of patients receiving chemotherapy (n = 53). SM, muscle density, VAT, SM/VAT, and BMI were associated with surgery‐related complications, and muscle density, IMAT, IMAT percentage, and SM/VAT were associated with long‐term survival. After Bonferroni correction, no CT‐based body composition measure was significantly associated with adverse outcomes. Higher BMI was associated with prolonged LOS. Conclusion The associations between CT‐based body composition measures and adverse outcomes of consecutive treatment modalities in older patients with CRC were not consistent or statistically significant. Implications for Practice Computed tomography (CT)‐based body composition, including muscle mass, muscle density, and intermuscular, visceral, and subcutaneous adipose tissue, showed inconsistent and nonsignificant associations with surgery‐related complications, dose‐limiting toxicity, and overall survival in older adults with colorectal cancer. This study underscores the need to verify whether CT‐based body composition measures are worth implementing in clinical practice.

Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as post‐operative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review, we summarize proposed pathophysiological mechanisms underlying the association between low skeletal muscle mass and poor clinical outcomes in older cancer patients including a) systemic inflammation; b) insulin‐dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics of anticancer drugs. The mechanisms of altered myokine balance negatively affecting the innate and adaptive immune system, and altered pharmacokinetics of anticancer drugs leading to a relative overdosage of anticancer drugs are best‐substantiated. The effects of glucose intolerance and circulating mitochondrial DNA as a consequence of low skeletal muscle mass are topics of interest for future research. Restoring myokine balance through physical exercise, exercise mimetics, neuro‐muscular activation and adapting anticancer drug dosing on skeletal muscle mass could be targeted approaches to improve clinical outcomes in older cancer patients with low skeletal muscle mass.

Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B are released by physically active muscle and cross the blood-brain-barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood-brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function, lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.

Physical and nutritional prehabilitation in older patients with CRC has not shown a significant reduction in postoperative complications or length of stay. One study that examined the effect of a perioperative nutritional supplement reported a reduction in postoperative complications. Future research should explore targeted combined interventions, taking into account physical and nutritional patient requirements.