18.3: Exercise and Cancer-Related Fatigue

18.3.1. Definition and Description

More than one-third of people will be diagnosed with cancer in their lifetime. Due to improvements in cancer prevention and treatment, more people are now living longer with and beyond cancer. Fatigue can be one of the principal concerns for people with cancer. The most widely accepted definition of cancer-related fatigue (CRF) is "a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning" (Berger et al., 2015, p. 1014). It can be hard to understand CRF if you have not personally experienced it, but compared with fatigue that can be experienced by healthy individuals, CRF is more severe (people with CRF describe it as "overwhelming" and "all-encompassing"), less likely to be relieved by rest, can limit daily activities, and can be debilitating (Scott et al., 2011). CRF is a significant clinical problem that has historically been under-recognized, especially in comparison to other common cancer symptoms such as pain or nausea. The experience of CRF can be highly individual, but there are several common clinical features that have been identified. Alongside significant fatigue and an increased need to rest, these features can include limb heaviness or weakness, problems with short-term memory, unrefreshing or non-restorative sleep, a perceived need to struggle to overcome inactivity, and emotional reactivity (Cella et al., 1998). CRF is assessed as a patient-reported outcome, and for routine screening in clinical practice, individuals are asked to self-report fatigue intensity over the past week on a scale of 0-10 (where 0 = no fatigue and 10 = worst fatigue). A score of ≥4 (where 0–3 = none to mild, 4–6 = moderate, and 7–10 = severe) helps identify fatigue as a problem and should be followed by a comprehensive fatigue assessment (Howell et al., 2013).

Cancer-related fatigue is common during active treatment (the period of weeks or months that a patient is receiving, for example, chemotherapy or radiation therapy), and this can be true for treatment delivered with both curative and palliative intent. Estimates of the prevalence of CRF vary due to differences in the methods used to measures CRF and differences in the specific population being assessed (considering there are many different cancer types and treatment protocols). However, fatigue does tend to worsen with the progression of the disease and can be more severe with multimodality or dose-intense treatment protocols. In the case of curative cancer treatment, fatigue resolves for most people in the weeks after the treatment has been delivered. However, for a sub-set of people, fatigue can become a chronic issue that can continue for years (Jones et al., 2016). This type of chronic CRF (also called post-cancer fatigue) can prevent people from returning to work and is associated with high levels of disability.

Although the mechanisms leading to CRF are not completely understood, it is well accepted that CRF is multidimensional and is influenced by a range of factors,including underlying biological mechanisms (Bower, 2014). Some of the factors that can contribute to CRF are psychosocial, including depression, anxiety, and lack of social support. People with CRF often report a lack of understanding from family, friends or doctors, and a lack of social and medical legitimacy for the symptom (Pertl et al., 2014; Rosman, 2009). CRF can lead to social isolation and disengagement, loss of identity, and feelings of guilt and frustration about fatigue (Corbett et al., 2017; C. Penner et al., 2020). CRF can be difficult to articulate, and there are barriers that prevent people with CRF from communicating with healthcare professionals about their fatigue, including not wanting to complain and a lack of awareness that there are effective treatments for fatigue (Passik et al., 2002). CRF is not trivial and more people now recognize the importance of the patient's experience. Clearly, CRF can have a significant impact on a person's overall quality of life.

18.3.2. The Role of Exercise in Treating Fatigue in People with Cancer-Related Fatigue

All people with cancer should avoid inactivity, be as physically active as current abilities and conditions allow,and return to daily activities as soon as possible following a cancer diagnosis (Cormie et al., 2018). However, for people with CRF, exercise can be considered first-line treatment. The mechanisms for the reductions of fatigue severity with exercise are not well understood but may include physiological factors such as increased cardiorespiratory fitness or reduced inflammation, and psychological factors, including reduced symptoms of depression, anxiety, and increased social support. Some of the evidence that supports exercise as a treatment for CRF is based on systematic reviews and meta-analyses. A systematic review is a methodical search of the literature that aims to summarize the current body of research. A meta-analysis is a statistical analysis that combines the results of multiple studies, often randomized controlled trials, and provides a high level of evidence on the effectiveness of an intervention. There are now several systematic reviews with meta-analyses on the topic of exercise for CRF. In 2020, van Vulpen et al. concluded that the beneficial effects of exercise on fatigue in patients with cancer are consistent across demographic and clinical characteristics. In 2018, Kessels et al.found that exercise has a large effect on CRF in cancer survivors and that aerobic interventions with high adherence have the best result. In 2017, Mustian et al. found that both exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. In perhaps the most comprehensive review to date, Oberoi et al. (2018) included 170 randomized controlled trials and found that physical activity significantly decreases the severity of fatigue in patients with cancer.

Although there are many studies on exercise for CRF, the body of research is not without limitations. In fact, in a systematic review of systematic reviews with meta-analyses, Kelley & Kelley (2017) concluded that more well-designed randomized controlled trials are needed because the results on exercise for CRF vary and are inconclusive. However, the researchers also noted that because exercise does not seem to make CRF worse and is associated with numerous health benefits, exercise programs that take into consideration the unique needs of cancer patients can be recommended. Another limitation is that some populations are underrepresented as most research is conducted on people diagnosed with breast cancer, whereas other cancer types have been overlooked. Similarly, most research includes interventions that are delivered during chemotherapy or radiation therapy, but there are far fewer studies on exercise for people with chronic CRF or for people with advanced cancer. Finally, the vast majority of studies do not specifically target participants with clinically relevant fatigue(Twomey et al., 2020), and this may contribute to the fact that although the beneficial effect of exercise of CRF is consistently demonstrated, the size of the effect (that is, the amount of improvement in fatigue) is usually only small to moderate.

In 2019, a consensus statement from an international multidisciplinary roundtable presented the most recent exercise guidelines for cancer survivors (Campbell et al., 2019). For some cancer-related health outcomes, there was consensus that the evidence was enough to recommend an exercise prescription based on the FITT principle (Frequency, Intensity, Time and Type). For CRF, the recommendation is to exercise three times per week at a moderate-to-vigorous intensity for 30 min, either as aerobic exercise or aerobic exercise plus resistance training. The FITT prescription provides a useful guideline, but exercise should be tailored to ensure the overall well-being of the individual. There is no "one size fits all" exercise prescription for CRF, and some people can exercise more frequently, for a longer duration or at higher intensities than the recommendations made by Campbell et al. (2019)without adverse effects. In contrast, a subset of people with CRF may experience a worsening of symptoms for multiple days after an exercise bout, and therefore, responses to exercise must be monitored carefully to avoid causing harm (Twomey et al., 2020). Finally, it can be counterintuitive or intimidating to become more physically active when you have CRF, and so support for behaviour change must also be considered alongside any exercise prescription.