Excessive muscle loss is commonly observed in cancer patients and its association with poor prognosis has been well-established. Cancer-associated sarcopenia differs from age-related wasting in that it is not responsive to nutritional intervention and exercise. This is related to its unique pathogenesis, a result of diverse and interconnected mechanisms including inflammation, disordered metabolism, proteolysis and autophagy. There is a growing body of evidence that suggests that the tumor is the driver of muscle wasting by its elaboration of mediators that influence each of these pro-sarcopenic pathways. In this review, evidence for these tumor-derived factors and putative mechanisms for inducing muscle wasting will be reviewed. Potential targets for future research and therapeutic interventions will also be reviewed.

Background Low muscle radiodensity on computed tomography (CT) scan, indicative of myosteatosis, is commonly observed in cancer patients and can be associated with poor prognosis. Radiodensity is typically measured at the level of the third lumbar vertebra (L3). It is unknown whether features at L3 reflect a systemic state affecting peripheral muscle groups, whether images used at different levels can be used as a surrogate if L3 images are unavailable, and how radiodensity varies between cancer types. Methods Core and extremity muscle radiodensities were measured in whole body CT images from melanoma patients to evaluate the anatomical distribution of muscle radiodensity measurements. Core muscle radiodensity was measured in 891 patients with different cancer types to study malignancy-dependent patterns in muscle radiodensity. Results Low muscle radiodensity at L3 (<30 Hounsfield Unit) was associated with a corresponding lower muscle radiodensity in all muscle groups evaluated (P < 0.001). However, muscle radiodensities were lowest in the core muscle groups compared with muscles in the extremities. Muscle radiodensities at T12 closely correlated with measurements taken at L3 (r = 0.920, P < 0.001), but the correlation was weaker with mid-thigh measurements (r = 0.745, P < 0.001). The distribution of muscle radiodensities varied significantly with cancer type (P = 0.002). Conclusions The uniform distribution of low muscle radiodensity in cancer patients supports the hypothesis that the underlying mechanism for myosteatosis is systemic in nature. The most reliable measurements of muscle radiodensity are taken using images of core muscles. Variations in muscle radiodensity associated with cancer exist, suggesting that cancer-specific biological drivers are at play.