A reason to hit the gym?

A new study shows that loss of muscle mass is significantly related to mortality in stage I to III colorectal cancer.  (see also, weight loss and mortality, https://csn.cancer.org/node/311659 )

https://onlinelibrary.wiley.com/doi/full/10.1002/jcsm.12305

In this large population‐based cohort study, we demonstrated that longitudinal declines in muscle mass and radiodensity are a risk factor for all‐cause and CRC‐specific mortality in patients with stage I–III CRC. The observed associations were independent of recurrent disease and changes in body mass and other body composition parameters including visceral and subcutaneous adipose tissue. Extrapolated from the abdomen to the whole body, moderate and large deteriorations in muscle mass are consistent with losses of 1.8 ± 0.6 and 4.4 ± 1.9 kg of skeletal muscle, respectively.22

Among 215 patients receiving first‐line chemotherapy for metastatic CRC, a >5% deterioration in muscle mass over 4 months was associated with a 2.1‐fold higher risk of mortality.9 A ≥9% deterioration over 3 months was associated with a four‐fold increase in the risk of mortality in a cohort of 67 patients receiving first‐line and second‐line chemotherapy for metastatic CRC.8 In our study, over 14 months we observed small overall changes in muscle mass (+0.1 ± 5.7%) and muscle radiodensity (−0.7 ± 10.1%). This is in contrast to patients with stage metastatic CRC, such that over 14 months it is estimated that patients lose, on average, 28.5% and 17.3% in muscle mass and muscle radiodensity, respectively.8 In a cohort of 1803 healthy older adults, each ≈4% decline in thigh muscle mass over 4 years was associated with a 20% increase in the risk of death, independent of weight loss and changes in adiposity.28

At the time of diagnosis, 30−60% of patients with CRC may have a low muscle mass or low muscle radiodensity.8, 29 Low muscle mass and low muscle radiodensity at diagnosis are risk factors for mortality.8, 29 Our analyses demonstrated that, independent of muscle mass or radiodensity at diagnosis, muscle wasting within the first 9−27 months after diagnosis was a risk factor for mortality. In subgroup interaction analyses, the prognostic importance of muscle wasting did not vary by baseline muscle mass or radiodensity. This suggests that muscle wasting may be deleterious among all patients, regardless of their body composition at diagnosis. The identified associations were independent of weight loss, suggesting that monitoring changes in body mass may be insufficient to promptly identify occult muscle wasting. CT images of the chest and abdomen is recommended every 6−12 months in patients with stage II and III CRC for the surveillance of recurrent disease.30 If our findings are replicated, it may provide empirical support to the viewpoint that quantifying body composition in routinely collected CT images will add value to patient care.18 Additional research is necessary to replicate the effect modification of cancer site on the relationship between change in muscle mass and risk of all‐cause mortality.

The observation that muscle wasting is associated with mortality may serve as a framework to test the hypothesis that interventions which prevent or **** muscle wasting may offer clinical benefit in this population. In this framework, the measurement of muscle mass and radiodensity may serve as therapeutic targets (i.e. biomarkers) to guide early‐phase intervention development. Muscle wasting is characterized by inflammation and oxidative stress, which activate the ubiquitin‐proteasome system and apoptosis‐inducing proteins, and suppress insulin‐like growth factors.31, 32 Pharmacotherapy development for muscle wasting has just begun to emerge.33 Participation in physical activity after diagnosis of stage I–III CRC is associated with a 40% relative reduction in the risk of mortality.34 Physical activity, particularly resistance exercise, is efficacious for preserving or improving muscle mass in adults35 and may be synergized when prescribed with nutritional supplementation.36 However, the efficacy of resistance exercise and nutritional supplementation in patients with stage I–III CRC has not yet been established.