Comparative efficacy of different exercise interventions for cancer-related fatigue, health-related quality of life, anxiety and depression symptoms in cancer survivors: a systematic review and network meta-analysis

Cancer survivors commonly experience persistent treatment-related symptoms including fatigue, reduced health-related quality of life (HRQoL), anxiety, depression, and physical function decline. Whilst exercise broadly benefits survivors, the comparative efficacy of specific exercise modalities remains insufficiently characterised to inform modality-specific clinical prescription. This network meta-analysis evaluated the comparative effectiveness of aerobic exercise (AE), resistance training (RT), combined aerobic-resistance training (CART), and mind–body exercises (MBE) across five symptom domains in cancer survivors. Systematic searches were conducted across MEDLINE, Scopus, CENTRAL, SPORTDiscus, and Web of Science. Eligible randomised controlled trials compared AE, RT, CART, or MBE against control conditions in adult cancer survivors (≥ 3 months post-treatment). Primary outcomes were cancer-related fatigue (CRF) and HRQoL; secondary outcomes were depression, patient-reported physical functioning, and objective cardiorespiratory fitness. Anxiety was examined via pairwise meta-analysis. Bayesian random-effects network meta-analysis was performed in RStudio, with treatment rankings quantified using SUCRA. GRADE was applied to primary outcomes. Fifty-seven trials involving 5,675 participants formed the evidence networks. For CRF, all modalities produced positive estimates relative to usual care. MBE ranked highest (SMD = 1.02, 95% CrI: 0.53 to 1.51; P-score = 0.97) and AE produced a statistically significant moderate effect (SMD = 0.54, 95% CrI: 0.10 to 0.98); however, substantial heterogeneity (I2 = 90.9%) and significant network inconsistency warrant cautious interpretation of fatigue rankings. GRADE certainty was moderate for AE and CART, and low for MBE and RT. For HRQoL, AE ranked first (SMD = 0.71, 95% CrI: 0.37 to 1.06; P-score = 0.92) with moderate certainty, and CART produced a significantly small-to-moderate effect (SMD = 0.34, 95% CrI: 0.05 to 0.63). CART demonstrated consistent benefits for patient-reported physical functioning (SMD = 0.53, 95% CrI: 0.29 to 0.76) and cardiorespiratory fitness (SMD = 0.55, 95% CrI: 0.14 to 0.96). Depression benefits were directionally consistent but non-significant across all modalities. Pairwise meta-analysis indicated a small but significant overall reduction in anxiety with exercise (SMD = -0.24, 95% CI: -0.47 to -0.01). All exercise modalities confer meaningful benefits across cancer survivorship outcomes, with intervention-specific advantages informative for symptom-guided prescription. AE demonstrated the most robust HRQoL benefits, CART produced the broadest physical functioning profile, and MBE ranked highest for fatigue, though with low certainty evidence. Modality selection guided by individual symptom priorities and patient preferences within existing clinical guidelines is supported by current comparative evidence. INPLASY2025110092.