Effects of a 6-Week Supervised Multimodal Exercise Program on Cancer-Related Fatigue, Quality of Life and Physical Function During Active Treatment: A Randomized Controlled Trial

<b>Background:</b> Reduced quality of life, cancer-related fatigue, and functional impairment are common during and after oncologic treatment. Although therapeutic exercise is effective, evidence on brief, supervised programs of moderate to vigorous intensity remains limited, despite their greater clinical feasibility. This study evaluated the effectiveness of a six-week multimodal Therapeutic Exercise Program (TEP) in patients with cancer. <b>Methods:</b> A randomized controlled clinical trial (NCT05816187) was conducted with 110 patients with cancer (stages I-III), assigned to either an intervention group (supervised TEP, three sessions per week for six weeks) or a control group (usual care). The program included cardiorespiratory and strength training with intensity monitored using the Rating of Perceived Exertion (RPE), as well as stretching exercises. Quality of life (QoL) was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F), functional capacity using the Six Minute Walk Test (6MWT), and muscle strength using the 30 Second Sit to Stand Test (30s-STST) and handgrip dynamometry (HGT). Analyses of covariance (ANCOVA), responder analyses based on the Minimal Clinically Important Difference (MCID), and effect sizes (ηp²) were performed. <b>Results:</b> The intervention group showed significant and clinically meaningful improvements in fatigue (FACIT-F: +4.53; <i>p</i> < 0.001; ηp² = 0.135), global QoL (+9.22; <i>p</i> = 0.006), physical function, functional capacity (+24.16 m in the 6MWT; <i>p</i> = 0.006), and muscle strength (30s-STST: +2.71 repetitions; handgrip: +3.32 kg; <i>p</i> < 0.001). A total of 63.3% of participants were responders for fatigue compared with 13.3% in the control group (NNT = 2.00). Functional improvements showed moderate correlations with fatigue and global health status. Among symptoms, only insomnia demonstrated a significant reduction. <b>Conclusions:</b> A brief, supervised, multimodal TEP of moderate to vigorous intensity appears to be an effective, safe, and clinically relevant intervention to improve fatigue, QoL, and functional capacity in patients with cancer, with potential applicability in multidisciplinary oncologic care.