This study explored the interconnections between sociodemographic elements, depression, fatigue, and exercise in patients suffering from incurable neoplasm, particularly emphasizing the mediating influence of exercise on the relationship between depression and fatigue This was a prospective, multicenter, observational study involving 15 hospitals across Spain. After three months of systemic cancer treatment, participants completed the Brief Symptom Inventory (BSI), the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and the Fatigue Assessment Scale (FAS) to measure levels of depression, fatigue, and exercise, respectively. A total of 616 subjects participated in this study. Activity levels differed markedly according to educational attainment, marital, and work status. There was a negative correlation between physical activity and depression, and a positive correlation between depression and fatigue (β = −0.18, and β = 0.46, respectively). Additionally, physical activity inversely influenced fatigue levels (β = 0.21). Physical activity served as a partial intermediary in the link between depression and fatigue among patients with advanced, unresectable cancer. Healthcare providers are urged to consider both the physical and emotional dimensions of cancer treatment, implementing physical activity programs to enhance overall patient quality of life and mental health.
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