The Determinants of Cancer-Related Fatigue: A Systematic Review

Abstract

Cancer-related fatigue (CRF) remains one of the most prevalent and functionally disruptive symptoms in oncology, yet its determinants are still frequently examined in isolation. This systematic review synthesizes recent evidence using an integrated model in which physiological, psychological, and treatment-related determinants shape fatigue severity, with sleep disturbance positioned as a probable mediating pathway and social support as a contextual moderator. A qualitative systematic synthesis aligned with PRISMA 2020 was conducted across PubMed, Scopus, Web of Science, and CINAHL for peer-reviewed studies published between 2021 and 2025. Of 274 records identified, 46 studies met the inclusion criteria and were retained for synthesis. The evidence consistently links inflammatory and metabolic dysregulation, pain burden, physical deconditioning, low activity, anxiety, depressive symptoms, treatment intensity, and advanced disease burden to higher fatigue severity. Recent evidence suggests that these determinants do not operate independently; rather, they accumulate across domains and cluster with poorer sleep. Sleep disturbance emerges as the most consistently implicated proximal pathway through which multidomain burden intensifies daytime fatigue, whereas stronger social support appears to attenuate fatigue escalation by buffering distress and supporting coping. The review contributes a study-by-factor matrix, a theory-informed synthesis, and an integrated conceptual framework for understanding variation in CRF severity across patients and care phases.