The conceptualisation of cancer-related fatigue: a systematic review

Cancer-related fatigue (CRF) is one of the most prevalent and distressing symptoms experienced by people with cancer, affecting individuals across the entire disease trajectory (Thong et al., 2020). It may arise during diagnosis, throughout active treatment, after treatment completion and during survivorship, as well as among those receiving palliative care (Berger et al., 2019; Poort et al., 2016). CRF differs from ordinary tiredness in its severity, persistence and limited responsiveness to rest (Cella et al., 1998; Jean-Pierre et al., 2007). Its consequences extend across physical, cognitive, emotional and functional domains, often impairing daily activities, employment and social engagement (Charalambous & Kouta, 2016; Corbett et al., 2016). Despite extensive research, substantial variation remains in reported prevalence estimates. Ma et al. (2020) identified a pooled prevalence of 52%, with wide variation across studies (14–100%). Kang et al. (2023) further demonstrated heterogeneity in the prevalence of mild, moderate, severe and moderate-to-severe fatigue, varying by cancer type, treatment stage, treatment modality and gender. A major contributor to this heterogeneity is the lack of consensus regarding how CRF is conceptualised and defined. Fatigue has been variously described as a subjective symptom, a clinical syndrome and a physiological process (Fernandez et al., 2020), resulting in inconsistencies across studies. It is important to emphasise that intervention is possible, with several targeted approaches showing promise in alleviating CRF. Nevertheless, a lack of suitable conceptualisation and clear definitions currently prevents these advancements reaching their full clinical potential. Resolving these ambiguities is therefore a clinical necessity, as it ensures that promising therapies can be evaluated and implemented for patient benefit. This variability limits comparability constrains meta-analytic synthesis and challenges the development of targeted clinical interventions. Calls for clearer definitions and multidimensional frameworks highlight the need to improve conceptual clarity in CRF research (Barsevick et al., 2010; Al Maqbali, 2021). Without standardisation, the underdiagnosis and undertreatment of CRF are likely to persist (Thong et al., 2020; Al Maqbali, 2021). Several theoretical frameworks attempt to explain the nature and mechanisms of CRF, reflecting its multidimensional character. Biological models attribute CRF to physiological dysregulation, variably implicating chronic inflammation, immune activation, Hypothalamic-Pituitary-Adrenal (HPA) axis disruption, altered neurotransmission and metabolic dysfunction (Bower, 2007; Yang et al., 2019; Yavuzsen et al., 2009; Li et al., 2025; Kanter et al., 2024). Psychological frameworks emphasise the roles of affect, cognition and interoception, including maladaptive illness perceptions, attentional biases and altered predictive processing of internal bodily states (Jacobsen et al., 2007; Brown & Kroenke, 2009; Penner et al., 2020; Arya et al., 2021; Janowitz et al., 2025). Behavioural models focus on cycles of inactivity, deconditioning and disrupted sleep-wake patterns, often reinforced by beliefs surrounding activity and rest (Donovan et al., 2008; Mock et al., 2007; Cramp & Daniel, 2012; Müller et al., 2021). Phenomenological perspectives highlight the lived experience of fatigue as a profound disruption of agency, vitality and embodied selfhood (Wu et al., 2007; Bootsma et al., 2023). Although these frameworks offer valuable insights, they also illustrate the fragmentation of the CRF literature. There is limited synthesis comparing how CRF is conceptualised across studies, and how theoretical perspectives inform definitional choices and measurement practices. This fragmentation contributes to inconsistent prevalence estimates, varied assessment tools and limited progress in developing mechanism-based interventions. Given these challenges, a systematic review is needed to map, compare and critically evaluate the conceptualisations, frameworks and theoretical models underpinning CRF research. By clarifying how CRF is defined and understood across the literature, this review aims to support greater consistency in future research, enhance interpretability across studies and contribute to the development of more cohesive and clinically actionable frameworks for CRF. Review questions Primary 1. What frameworks exist to conceptualise cancer-related fatigue (CRF) in the literature? Secondary 2. How is CRF conceptualised within those frameworks (domains, components)? 3. Who are the frameworks intended for (patients, clinicians, researchers, policy makers)? 4. What do the frameworks focus on (biological, psychological, behavioural, social, measurement)? 5. Where is there consensus or disagreement between frameworks? 6. What gaps and challenges are identified when researchers conceptualise CRF? Objectives Primary objective 1. To identify and synthesise the conceptual frameworks, models and theories used to conceptualise cancer-related fatigue (CRF) in the published literature. Secondary objectives 2. To examine how CRF is conceptualised within these frameworks, including their proposed components, domains and underlying assumptions. 3. To identify the intended audience or user group for each framework (e.g., patients, clinicians, researchers, policy makers). 4. To describe the primary focus of each framework, including biological, psychological, behavioural, social and measurement-based approaches. 5. To compare areas of convergence and divergence across frameworks, identifying where consensus exists and where discrepancies remain.