Muscle Health and Prognosis in Patients With Cancer: New Insights

BACKGROUND: Reduced muscle mass and impaired composition have each been independently associated with worse outcomes in patients with cancer. However, emerging evidence suggests that reduced muscle strength-namely, dynapenia-may be particularly important for prognostication, as it is easier to assess in clinical practice compared to muscle mass. Importantly, muscle mass and composition-as assessed with computed tomography images-may not fully capture key physiological changes and/or reflect whole-body alterations, particularly in patients who remain within the normal range. We investigated the predictive power for mortality of low muscle mass and impaired composition, weight loss (WL) and low strength, as well as their combination, in a cohort of patients with cancer. METHODS: Baseline data on muscle mass and radiodensity (Hounsfield units [HU]) at the L3 level-assessed using computed tomography-along with 6-month unintentional WL (relevant if ≥ 10% of usual body weight) and muscle strength by handgrip were pooled for 477 patients with cancer (59.1% male, mean age 61.2 ± 12.8 years) from studies conducted in Brazil, Canada and Italy. Patients were categorized by sex and body mass index-specific cutoffs for low skeletal muscle mass index, low skeletal muscle radiodensity, WL ≥ 10% and low handgrip strength. Patients were followed for at least 12 months until death or censoring. RESULTS: During a median follow-up of 43 months (IQR: 28-83), 188 patients died. Kaplan-Meier analysis showed no survival differences for low skeletal muscle index or low radiodensity, regardless of handgrip strength. Only WL ≥ 10% consistently identified patients with poorer prognosis, independently of low handgrip strength. Fully adjusted Cox's regression models showed an independent association only with WL (HR = 1.56 [95% CI: 1.12;2.16]; p = 0.008) and low handgrip strength (HR = 2.07 [95% CI: 1.47;2.92]; p < 0.001), as well as an increased risk for all low handgrip strength/%WL categories. Mortality risk increased across all low handgrip strength/%WL categories. Among the eight risk groups combining low skeletal muscle mass index, WL ≥ 10% and low handgrip strength, only those including WL ≥ 10% and low handgrip strength were significantly associated with higher mortality. Low skeletal muscle mass index contributed to a worse prognosis only when combined with both WL ≥ 10% and low handgrip strength. Similar results were observed when skeletal muscle radiodensity was used in replacement of skeletal muscle mass index. CONCLUSIONS: In patients with cancer, muscle strength and WL were stronger survival predictors than muscle mass and composition, reinforcing their relevancy as easily assessed key markers of muscle health.