Change in skeletal muscle mass during systemic cancer treatment: a systematic review and meta-analysis

BACKGROUND AND PURPOSE: Loss of skeletal muscle mass (SMM) is common during systemic cancer treatment, but the magnitude and variability across cancer and treatment types remain uncertain. We aimed to describe changes in SMM during systemic cancer treatment supported by pooled quantitative estimates. PATIENTS/MATERIAL AND METHODS: We systematically searched PubMed, Embase, and Web of Science until April 2025 for longitudinal studies reporting SMM during chemotherapy and/or immunotherapy (± targeted therapy) in patients with cancer (PROSPERO CRD42022308388). Standardized mean changes (SMC) were pooled in random-effects meta-analyses using the restricted maximum-likelihood estimator with Hartung-Knapp adjustment. Heterogeneity was assessed using I². Risk of bias was assessed with the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Seventy-eight studies (n = 10,502; 52% male; median age 64 years [interquartile range, IQR: 34-77]) were included. Meta-analysis across cancers showed an association between systemic cancer treatment and decline in SMM (59 studies; n = 6,373; SMC = -0.24, 95% confidence interval [CI]: -0.29 to -0.20; I² = 92%), corresponding to -5% over a median interval of 90 (IQR: 71-129) days among studies (62%) reporting assessment intervals. Declines were most pronounced during chemotherapy (± targeted therapy). INTERPRETATION: Declines in SMM are frequently observed during systemic cancer treatment, particularly during chemotherapy (± targeted therapy), although effect sizes were generally small per Cohen's thresholds. However, substantial heterogeneity limits interpretation of a single pooled estimate. Prospective studies with standardized methods are needed to clarify trajectories, mechanisms and clinical implications of SMM loss.