Fatigue

A literature review into radiotherapy-induced fatigue by Jereczek-Fossa et al.^{Reference Jereczek-Fossa, Marsiglia and Orecchia6} states that fatigue can affect a patient’s wellbeing more than any other treatment-related side effects, with many prostate cancer patients ranking fatigue as being more impacting to their quality of life than lower urinary tract symptoms (LUTS). Research by Aghili et al.^{Reference Aghili, Farhan and Rade11} supports this statement, finding that patients viewed fatigue more adversely impacting than pain, sexual dysfunction and other treatment side effects. Vashistha et al.^{Reference Vashistha, Singh, Kaur, Prokop and Kaushik12} found that fatigue impacts physically, physiologically and psychologically, and is the major contributor to poor quality of life in cancer patients.

Although widely researched, the cause and prevalence of radiotherapy-induced fatigue are not fully understood and commonly underestimated by health care professionals.^{Reference Jereczek-Fossa, Marsiglia and Orecchia6,Reference Windsor, Potter, McAdam and McCowan13–Reference Stone, Richards, A’Hern and Hardy15} Kinney et al.^{Reference Kinney, Blair and Guest14} state that fatigue is common, yet it is under-recognised and under-treated, leading to patients becoming isolated, less active and physically deconditioned, contributing to the exacerbation of fatigue levels during treatment. Within current literature, there is limited evidence to support current ‘standard care’ for fatigue management. Patients experiencing fatigue are frequently advised to rest and avoid strenuous physical activity. However, new research has found this to be counterproductive and potentially detrimental to patients’ quality of life.^{Reference Horgan and O’Donovan1,Reference Windsor, Nicol and Potter16} Prolonged inactivity in prostate cancer patients due to treatment causes declined physical functioning and reduced fitness, which, in turn, negatively impacts quality of life. Evidence by Monga et al.^{Reference Monga, Garber and Thornby17} reports fatigue incidences ranging from 68 to 100% in prostate cancer patients undergoing radiotherapy. Due to the huge impact fatigue has on patients’ quality of life, Aghili et al.^{Reference Aghili, Farhan and Rade11} state that it is imperative to find a non-invasive, non-pharmacological cost-effective solution to fatigue management.

Exercise

Exercise is renowned for its multitude of physical and physiological health benefits, while reducing feelings of depression and benefitting cognitive function, resulting in improvement to overall wellbeing.^{Reference Drouin and Beeler18,Reference Patel, Alkhawam, Madanieh, Shah, Kosmas and Vittorio19} New knowledge and understanding into the benefits of exercise have unearthed a growing interest in the potential of prescribed exercise therapy, especially in cancer patients. Although most studies focus on breast cancer, some studies have reviewed the potential impact of exercise on radiotherapy-induced fatigue in prostate cancer patients.

A comprehensive systematic review of 13 RCTs involving 1,057 prostate cancer patients across multiple centres was undertaken by Vashistha et al.^{Reference Vashistha, Singh, Kaur, Prokop and Kaushik12} into the effects of exercise on fatigue. This review reported that 96% of patients involved in these studies experienced radiotherapy-induced fatigue. Adopting the Cochrane Collaboration tool for risk of bias assessment, the authors highlighted that ten of the 13 eligible trials had a high risk of bias with seven having poor attrition rates. Many of these studies had limited descriptions of the interventions and selective reporting in favour of their primary objective. However, this review concluded, from the combined evidence, that exercise interventions did improve radiation-induced fatigue and quality of life in prostate cancer patients.

Drouin & Beeler’s review^{Reference Drouin and Beeler18} of exercise and urology cancers also concludes that exercise has the potential to positively impact patients’ physical and physiological wellbeing, stating that exercise would provide unique benefits in the management of treatment side effects and may be necessary in the prevention of fatigue. However, research into the most effective exercise programme is still under debate, with trials focusing on various training aspects, such as exercise type, intensity, frequency and duration. Although most studies have focused on Aerobic training and Resistance training, alternative exercise traditions, such as Pilates, Yoga, Tai Chi and Qigong, have recently become more popular in fatigue management exploration.

Aerobic exercise

The majority of research studies explore the use of aerobic exercise programmes for fatigue management. This is mainly due to the simplistic nature of aerobic exercise, as it is defined as any type of cardiovascular conditioning, such as walking, running, or cycling.^{Reference Patel, Alkhawam, Madanieh, Shah, Kosmas and Vittorio19} Such exercises can be seamlessly implemented into daily routine without major impact. This training depends primarily on the aerobic energy generating process, which involves oxygen, and can be of low to high intensity.^{Reference Patel, Alkhawam, Madanieh, Shah, Kosmas and Vittorio19}

A prospective RCT carried out by Windsor et al.^{Reference Windsor, Nicol and Potter16} focused on the impact of a 4-week aerobic exercise programme on radiotherapy-induced fatigue in prostate cancer patients. The study included a cohort of 66 men undergoing prostate radiotherapy, 33 being placed in a control group and 33 in an aerobic exercise intervention group. The exercise intervention employed was a 4-week home-based, moderate intensity, continuous 30-minute walking programme, three times per week. Patients in the control group were given standard advice to rest if they became fatigued and continue with daily activities. Windsor et al.^{Reference Windsor, Nicol and Potter16} conducted a robust study with a definitive result in favour of aerobic exercise in the prevention and management of fatigue. However, this study fails to address its limitations including being a single centre study, which only illustrates the results of a small sample of patients. Furthermore, patients enrolled into this study mainly had a diagnosis of early stage prostate cancer, hence may be in a better physical condition than those with more advanced prostate cancer, and therefore, findings may not be generalizable to all prostate cancer patients.

A review of current literature by Luan et al.^{Reference Luan, Tian, Zhang, Huang, Li and Wang20} into exercise as a prescription for various diseases supports the findings of Windsor et al.^{Reference Windsor, Nicol and Potter16} One hundred eighty-eight articles reporting on RCTs were included for data analysis with the primary focus of exercise intervention. Luan et al. state that aerobic exercise for prostate cancer patients increases activity levels, improves cardiovascular health and reduces fatigue. They describe a walking programme, by Pernar et al.,^{Reference Pernar, Fall and Rider21} which is similar to that of Windsor et al.,^{Reference Windsor, Nicol and Potter16} which concluded that implementing 10,000 steps per day has an overall positive impact on patient fatigue during treatment. This review also promotes the clinically significant role of exercise therapy as a fatigue management strategy. However, this review does not solely focus on prostate cancer, and it is not clear how many prostate cancer studies were used in the findings and if counter arguments were addressed.

An RCT carried out by Monga et al.^{Reference Monga, Garber and Thornby17} reviewed the impact of an 8-week supervised cardiovascular conditioning programme on fatigue prevention and quality of life improvement in men with localised prostate cancer undergoing radiotherapy. This two-armed, single centre study included 21 men, enrolled in either a prevention group or ‘standard care’ group. In comparison with Windsor et al.’s^{Reference Windsor, Nicol and Potter16} self-directed home-based programme, Monga et al.’s intervention group participated in a structured programme led by a kinesiotherapist and supervised by a physician. Pre- and post-radiotherapy main outcome measures were recorded including fatigue, cardiac fitness, depression, physical functioning and social wellbeing. It was noted that no significant difference between groups was recorded prior to radiotherapy. However, clinically significant improvements were documented in the exercise intervention group post-assessment. Monga et al. concluded that the implementation of a cardiovascular exercise programme can prevent fatigue and improve quality of life; however, due to their small cohort of patients, the results of their study were limited and cannot be generalised.

Overall, more research is required to establish the extent of the benefits of aerobic exercise for patients with prostate cancer, especially those with more advanced disease.

Resistance exercise

Resistance exercise, defined as exercise that focuses on improving muscular strength and endurance,^{Reference Bird, Tarpenning and Marino22} has also received some investigation. This exercise can take many forms, including traditional weightlifting, bodyweight exercises or resistance band exercises.^{Reference Bird, Tarpenning and Marino22}

Segal et al.^{Reference Segal, Reid and Courneya23} carried out an RCT of usual care versus resistance versus aerobic exercise in men undergoing radiotherapy for prostate cancer. This three-armed, single-centre study was carried out over a 3-year period and incorporated 121 men. The primary endpoint was the comparison of fatigue between groups. The ‘Functional Assessment of Cancer Therapy–Fatigue scale’ assessed fatigue levels at baseline, 12 and 24 weeks. Data from this study showed that both training regimes mitigated acute fatigue, but resistance training also produced long-term improvements in patients’ fatigue and quality of life. Segal et al. state that the strengths of this trial include a large sample size, a well-defined population, supervised exercise regimes and a comprehensive assessment of endpoints, highlighting that supervised exercise regimes have the added benefit of high levels of patient compliance, providing rigor and reliability. However, despite being of high methodology quality, this study has weaknesses that have not been addressed. The sample size, although quoted as large, is relatively small on a global scale, with a heterogeneous group of patients. Though primary endpoints were regularly assessed, a self-assessment tool was used, which is open to subjectivity. Overall, this study does find correlations between exercise and reduced fatigue, and authors do support the use of structured exercise regimes for prostate patients undergoing radiotherapy as a mechanism for fatigue prevention. This study also highlights the superior, favourable long-term effects of resistance training that previous studies fail to address.

A systematic review of 17 RCTs by Menichetti et al.,^{Reference Menichetti, Villa and Magnani24} looking at various lifestyle interventions to improve quality of life in men with prostate cancer, supports results by Segal et al.,^{Reference Segal, Reid and Courneya23} in the use of resistance training. Although this review looked at various lifestyle interventions, it was noted that exercise was the most frequently implemented non-medical intervention and showed the most positive results compared to diet and combined interventions. Menichetti et al. found that in most studies, resistance training yielded the most positive effects, significantly improving fatigue, physical functioning and wellbeing when compared to aerobic exercise. However, the main limitation of this study was the variation in the quality of trials included; therefore, primary endpoints, although in favour of resistance exercise, are restricted.

Three hundred ninety-two participants were explored in a systematic review by Horgan et al.,^{Reference Horgan and O’Donovan1} into exercise during radiotherapy for prostate cancer patients. Horgan et al. found exercise to be effective in preventing fatigue but concluded that the impact of exercise on quality of life was not significant. Due to limited evidence, it was not feasible for Horgan et al. to analyse effects of resistance training in depth. However, like Segal et al.,^{Reference Segal, Reid and Courneya23} this review does conclude that post-treatment results showed resistance training to be more advantageous in fatigue management when compared to control groups and aerobic exercise. This study also addresses the benefits of supervised programmes, alluding to better patient compliance. Although a large sample size was used for this study, inter-study samples were relatively small and focused on single exercise interventions and regimes. This limits results of comparison exercise interventions, and therefore, as with previous studies, a clear superior exercise programme cannot be definitively concluded.

Alternative exercise

In recent years, there has been a surge of interest in alternative exercise traditions as methods of rehabilitation and symptom management for cancer patients. Movement-based mind-body practices, such as Yoga, Tai Chi and Qigong, could improve treatment side effects and enhance physical functioning and overall quality of life.^{Reference Drouin and Beeler18}

Ruddy et al.^{Reference Ruddy, Stan, Bhagra, Jurisson and Cheville25} state that yoga is the most popular and scientifically studied alternative exercise regime. Again, studies in research mainly concentrate on breast cancer with research data supporting the use of yoga to benefit prostate cancer patients, being limited. A review of current RCTs in the use of alternative exercise methods by Ruddy et al.^{Reference Ruddy, Stan, Bhagra, Jurisson and Cheville25} did conclude significant benefit of yoga for fatigue and quality of life in cancer patients. This study characterises yoga as a versatile, non-strenuous alternative to traditional physical activities previously discussed, which is individually adaptable to each patient’s ability, regardless of physical status and can aid in symptom management such as fatigue. This type of exercise does show benefit; however, more research is required at different cancer sites before implementation.

Tai Chi and Qigong are low-impact meditative mind-body exercise interventions that improve holistic wellbeing.^{Reference McQuade, Prinsloo and Chang4} McQuade et al.^{Reference McQuade, Prinsloo and Chang4} conducted an RCT where 76 patients with localised or advanced prostate cancer were split into three groups; a control group, a light resistance exercise group and a Qigong/Tai Chi group. Outcome measures included sleep duration and fatigue for a period of 3 months post-radiotherapy. This study concluded that the Qigong/Tai Chai intervention increased sleep duration temporarily but did not have a significant impact on fatigue levels. Strengths of this study include high adherence to activities throughout the study period, but a limitation was that it excluded those with physical walking disabilities, and therefore, the findings may not apply to all patients with prostate cancer. This study was also relatively small in terms of population size. Campo et al.’s^{Reference Campo, Agarwal and LaStayo26} small RCT with 40 prostate cancer patients randomised patients into either 12 weeks of Qigong or stretching exercises. In contrast to McQuade et al.’s results, they found that the Qigong group had significantly improved fatigue levels compared to the stretching exercise group. The difference between these two studies findings may be attributable to the differences in baseline fatigue with McQuade et al.^{Reference McQuade, Prinsloo and Chang4} describing their participants as having generally mild fatigue at baseline, while Campo et al.’s study only included patients who had a minimum threshold level of fatigue. A ceiling effect may have occurred with McQuade et al.’s results where differences in outcomes were harder to detect due to their favourable baseline score.

Kinney et al.,^{Reference Kinney, Blair and Guest14} the team involved in Camp et al.’s previous study, are currently conducting an ongoing large, multi-centre, three-armed clinical trial reviewing the biobehavioural effects of Tai Chi in men with prostate cancer compared with body training and usual care. Although this is an ongoing area of study and the results to date are not conclusive, Kinney et al. hypothesize that the use of alternative exercises may be valuable for treatment of fatigue in prostate cancer patients due to its low intensity and suitability for all age groups regardless of prior activity level. Considering this aspect, Tai chi or Qigong could bridge the gap as an exercise programme that is potentially suitable for all prostate patients irrespective of stage, age or physical ability.