Exercise and cancer survivorship

Authors:

Details:

  1. Edith Cowan University Health and Wellness Institute, Edith Cowan University, Joondalup Western Australia, Australia.
  2. School of Public Health and Social Work, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
  3. School of Exercise and Nutrition Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
  4. Centre for Medical Psychology and Evidence-based Decision Making, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia
  5. ONTrac at Peter Mac, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  6. School of Exercise Science, Australian Catholic University, Strathfield, New South Wales, Australia.

Abstract

Exercise has been identified as an integral component of comprehensive survivorship care and a promising adjuvant therapy to aid in the management of cancer. Leading organisations worldwide now advocate exercise for cancer survivors. Here we briefly review the existing evidence for exercise and survivorship, as well as current research endeavours in Australia. Discussion extends to identify the gaps between research and practice, as well as future research directions needed to drive the field forward. With continued efforts by scientists, clinicians and consumers, there is real potential to strengthen the nexus between scientific evidence and clinical practice and integrate exercise into standard cancer care.


Exercise is considered a safe and effective treatment for people with cancer.1-3 Research to date has predominately evaluated the impact of exercise among people with localised breast and prostate cancer, however evidence is building for other types and stages of cancer. Clinical research over the last three decades has established the efficacy of exercise in counteracting many of the adverse treatment-related side-effects of cancer. To date, the strongest evidence exists for improving physical function, including aerobic fitness, muscular strength and functional ability,4 attenuating cancer-related fatigue,5 improving quality of life across multiple general health and cancer-specific domains,3 and alleviating psychological distress.6 Emerging evidence highlights that participation in exercise during or following cancer treatment reduces risk of developing new cancers and comorbid conditions, such as cardiovascular disease, diabetes and osteoporosis,1 counteracts unfavourable changes in body composition,7 can minimise sexual dysfunction,8 decreases pain,9 and enhances sleep quality.10

Further, observations from epidemiological evaluations suggest there is a protective effect of exercise against cancer recurrence and/or cancer specific death in breast, colon and prostate cancer but insufficient evidence for other cancers.2 Specifically, these observational data show that a higher level of physical activity is associated with a 20-60% risk reduction depending on cancer type in cancer-specific mortality when compared with those who are least active.2 Importantly, appropriately prescribed and supervised exercise has been consistently observed to be safe for many groups of cancer patients and survivors, including those with advanced disease.11 Collectively, this compelling literature has contributed to the development of exercise and cancer guidelines, which have subsequently been endorsed by major health organisations.11-14

Current exercise guidelines arose from a consensus statement developed by the peak professional body in exercise science worldwide, the American College of Sports Medicine.11 These guidelines extend the previous position statement by Australia’s exercise science organisation, Exercise and Sports Science Australia,12 and have been incorporated into physical activity recommendations promoted by the American Cancer Society,13 and the National Comprehensive Cancer Network.14 These guidelines promote: a) avoidance of inactivity; b) progression towards return to normal activity; and c) participation in at least 150 minutes of moderate-intensity or 75 minutes of vigorous intensity aerobic exercise (e.g. walking, jogging, cycling, swimming) weekly, and two to three resistance exercise sessions each week involving moderate to vigorous intensity exercises targeting the major muscle groups (i.e. lifting weights). While the guidelines are similar to exercise guidelines for adults,15 cancer type, presence and severity of treatment-related adverse effects, functional state, and cancer-specific precautions need to be considered when identifying optimal exercise prescription for people with cancer. This is a critical caveat which dictates that appropriate screening, prescription and monitoring is required to ensure safety and maximise efficacy in cancer survivors.11,13,14

The term ‘physical activity’ applies to any movement produced by skeletal muscles that requires the body to exert energy. In contrast, ‘exercise’ is structured physical activity for the purpose of conditioning the body to improve health and fitness. Research has firmly established the relationship between participation in physical activity and improvements in both the general and cancer-specific health and wellbeing of survivors. Recent epidemiological evidence demonstrates that it is not only participation in physical activity that is important for cancer-specific and all-cause mortality, but also the amount that is performed at a moderate to high intensity – that is, at a brisk walking pace or greater.16-18 This is consistent with decades of exercise science research involving healthy adults and various disease groups, establishing a clear dose-response relationship between exercise and health benefits.19-22 The specific physiological adaptations to exercise are dictated by the exercise modality performed, and the magnitude of adaptation dictated by the intensity and volume of exercise, relative to the starting point of the individual. Specific exercise is particularly important for counteracting insulin resistance, sarcopenia and declines in cardiorespiratory fitness. While the message for survivors to remain physically active is clearly important, targeted prescription of progressive exercise at an appropriate intensity and volume can optimise benefits to health and wellbeing in cancer survivors.

Current research in Australia

A systematic search of the Australian New Zealand Clinical Trials Registry, Australian Cancer Trials and clinicaltrials.gov databases was conducted to provide a comprehensive overview of the current research trials ongoing in Australia. All trials involving a specified exercise intervention in adult cancer survivors with a site in Australia and an enrolment status of ‘recruiting’, ‘not yet recruiting’ or ‘closed’; follow-up continuing as of July 16, 2014 were included. Registered trials that hadn’t been updated in the last five years were assumed to be completed, or with published outcomes were omitted. A total of 26 clinical trials were identified.

The majority of exercise intervention trials currently ongoing in Australia involve clinic-based programs (table 1). The 17 trials target 1639 participants diagnosed with breast (six trials; n = 379), prostate (five trials; n = 780), lung (three trials; n = 206), bowel/colorectal (two trials; n = 124) and haematologic (one trial; n = 150) cancers. There are a range of outcomes being evaluated, with primary analyses planned for exercise-related variables such as physical activity levels, physical function and cardiopulmonary fitness, as well as general and cancer-specific health issues, including sexual wellbeing, fatigue, body composition, bone mineral density, cognitive function, natural killer cell activity, lymphoedema incidence and severity, and pelvic floor symptoms. The duration of the exercise interventions range from one to 12 months, with an average length of 3.5 ± 2.6 months. Interventions involve an average of 2.3 ± 0.8 exercise sessions per week (range: one to four per week). For the majority of trials, sessions are supervised by an accredited exercise physiologist (AEP) (11 trials; n = 1355), physiotherapists (four trials; n = 204) and fitness trainers (two trials; n = 80). The majority of the interventions incorporate a combined prescription of aerobic and resistance exercise (12 trials). Programs currently underway are also delivering resistance only (three trials) aerobic only (one trial) exercise, as well as yoga (one trial). Impact exercise such as jumping, skipping, hopping and bounding prescriptions have been incorporated into the two trials examining bone mineral density as a primary outcome. Unfortunately, the intensity of the exercise wasn’t specified for the majority of the trials (eight trials), with six trials requiring a moderate to vigorous intensity in line with current guidelines and the remaining three specifying a low, moderate or low-moderate intensity of exercise. Eleven of the trials indicated that the exercise prescription was individualised. Nine of the studies incorporate various other elements to the intervention. One trial was non-randomised with no comparator/control group.

Table 1: Summary of registered trials involving clinic-based exercise interventions for cancer patients and survivors currently ongoing in Australia. †

Nine of the ongoing trials in Australia incorporate predominately home-based exercise interventions (table 2). These trials are targeting a total of 1672 cancer survivors, with over half of these participants (n = 962) involved in an international trial, with participating sites in Australia.21,22 This large trial involves survivors diagnosed with colon cancer, with the remaining trials targeting breast (2 trials; n = 300), haematologic (2 trials; n = 160), prostate (2 trials; n = 70), gynecologic (1 trial; n = 30) cancer survivors, as well as survivors with any form of cancer (1 trial; n = 150). Similar to the trials involving clinic-based exercise interventions, a wide variety of outcomes are being evaluated in these studies, with primary outcomes including disease-free survival, fatigue, physical activity level, body composition, quality of life, incontinence, lymphoedema incidence and muscle strength. The majority of these trials (eight trials; 98% of participants) incorporate ongoing support from AEPs, physiotherapists or fitness trainers by either face-to-face and/or telephone. The nature and frequency of ongoing support varies considerably across the interventions. Similarly, the duration of intervention length varies widely, from two months to three years. The exercise prescription wasn’t well defined for most trials in terms of the type and intensity of exercise involved. Eight trials specified that the program is to be individualised. Two of the trials incorporated behavioural support and two dietary education, in conjunction with the exercise program.

This body of ongoing research will address a number of areas warranting investigation. While for many cancers, efficacy of exercise is established, the optimal prescription variables such as type, intensity and duration require further investigation. Likewise, evaluation of modes of delivery that overcome barriers of distance and access are important for wide-spread reach and will make an important contribution to the field. The current research also addresses contemporary survivorship concerns such as sexual wellbeing, sleep disturbance and neuropathy, where exercise may play an important role in the future, and provide further rationale for the role of exercise as part of standard clinical care. While the search is limited only to projects that progressed to the stage of being registered in a primary clinical trials registry, and doesn’t include other forms of research, our results give an overview of the important work being undertaken in this space in Australia.

Table 2: Summary of registered randomised control trials involving home based exercise interventions for cancer patients and survivors currently ongoing in Australia.

Gaps between research and practice

The majority of Australian cancer survivors do not reach sufficient levels of physical activity (~40%) or are completely inactive (~33%).23 This is despite endorsement from major cancer organisations nationally and internationally, as well as the reported desire of cancer survivors to participate in appropriately designed and supervised exercise programs.24,25 Physical activity levels decrease significantly after diagnosis, and often don’t return to pre-morbid levels.26,27 The development of evidence-based programs that incorporate best practice exercise prescription, implemented by qualified allied health professionals (AEPs), and that are systematically available throughout Australia may be required. However, a multifactorial approach is needed to overcome significant challenges, including issues related to access and equity, consumer perceptions, integration with clinical practice and access to clear referral pathways.

The vast majority of the evidence has resulted from interventions delivered by health professionals. In order to optimise the benefits of exercise while maximising safety, the recommendation of exercise to a cancer survivor needs to be coupled with a referral to a qualified exercise professional. AEPs are four-year tertiary trained allied health professionals, most appropriate to provide exercise services for the prevention and management of chronic diseases and/or complex medical conditions. These specialists are highly skilled in identifying the optimal exercise prescription, which takes into account individual need, goals and circumstances. Based on current evidence, it is clear that cancer patients and survivors will benefit from the incorporation of exercise within their treatment and survivorship care plans. As such, moves to incorporate AEPs within multidisciplinary oncology teams are warranted in order to provide integrated care through dedicated exercise consultations. While this level of access to AEPs is not yet readily available throughout Australian hospitals and treatment centres, specialists and other oncology health professionals can refer patients to one of a growing number of AEPs practicing throughout Australia (there are approximately 3000 AEPs currently registered and searchable through an online directory at www.essa.org.au/find-aep/). Currently, cancer patients and survivors are eligible for up to five Medicare subsidised visits to an AEP annually through the Chronic Disease Management Plan.

Future directions

There is a pressing need for prospective randomised control trials of exercise interventions that involve best practice prescription, investigating cancer progression and survival outcomes. These large scale trials, accompanied by extended follow-up, are warranted based on promising epidemiological and animal model evidence.2,28 Data from such trials are critical to realising the role of exercise as an adjunct therapy for the management of cancer. They are theorised to be the stimulus required to incorporate high quality exercise programs as part of standard cancer care by providing the impetus for: funding of cancer specific exercise programs; oncology specialists to refer patients; and for survivors to participate. Importantly, the optimal exercise prescription for improvement in disease outcomes is yet to be established, especially with regards to the dose and timing of exercise, and whether potential effects vary by cancer site, stage or treatment factors. Canada is leading the field in this area, reporting trends towards improved disease-free survival in an exploratory analysis of breast cancer survivors (START trial).29 As well as launching the first prospective, randomised control trial of an exercise intervention on outcomes of survival in colon cancer, which is currently open for enrolment at 26 centres in Australia (CHALLENGE trial).30,31

There are over 100 different types of cancer with various disease trajectories and numerous treatment options, combinations and sequences. This diversity leads to a unique series of adverse physiological side-effects that dictate the need for targeted exercise interventions based on disease and treatment variables.32 Despite increased research efforts to explore the safety and efficacy of various exercise prescriptions for cancer survivors, there is a dearth of knowledge regarding these effects in a large number of cancer types. Research teams in Australia are starting to investigate relatively understudied cancer groups such as lung and gynaecological cancers, including cancers with poorer prognoses exemplified by pancreatic, brain and mesothelioma cancers. However, more research is required to determine targeted exercise prescription in these survivors. Furthermore, there are little data available to direct practice for advanced and palliative cancer groups. Based on the available early evidence in this area,33-38 exercise programs show promise in providing significant functional and quality of life benefits to survivors. Importantly, these patients report a desire and perceived ability to participate in exercise programs.39 Future research in these areas is warranted.

There remain important research questions requiring rigorous scientific investigation to advance understanding in the field of exercise and cancer. Some of the main areas warranting investigation include evaluating the effect of exercise on contemporary survivorship concerns, including understudied but problematic treatment-related effects such as cognitive decline, sexual dysfunction, compromised sleep quality, establishing cost-effectiveness and cost-utility, exploring mechanistic pathways, and developing the use of technology to overcome issues of equity and access. There is also a need to evaluate the effectiveness of systematic community-based exercise programs that can be administered as a standard supportive care service for cancer survivors throughout Australia.

In conclusion, the evidence demonstrating the benefits of exercise during and following treatment for cancer continues to mount. Further international efforts, with Australians significantly contributing to these, are underway to address current gaps in the literature. However, for the benefits of exercise to be realised on a global-scale, the greater challenge will be to translate what we know to be efficacious exercise programs in the research setting into effective programs in the community.

Acknowledgements
PC is supported by the Cancer Council Western Australia Postdoctoral Research Fellowship.

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