Exercise for managing cancer- and treatment-related side effects in older adults

Abstract

The incidence of cancer in adults aged 60 years and older is expected to rise, and because cancer is associated with aging, the overall prevalence of cancer will rise as well. With advances in cancer treatment, more older adults will receive treatment but they will also suffer the biopsychosocial consequences of cancer and cancer treatment. In this review, we describe the importance of assessing biopsychosocial needs in this vulnerable population and highlight studies supporting the use of exercise in addressing these needs. We discuss challenges and research gaps in several areas including 1) Identifying the exercise doses and modes for specific outcomes, 2) Understanding risks and safety of exercise, and 3) Implementing exercise programs into clinical practice at the individual, health care team, and organizational levels, including strategies to increase adherence.

Introduction

The world's population is expected to increase from 7.2 billion in 2015 to 9.7 billion in 2050, and adults aged >60 years constitute the group with the highest projected growth rate.¹ As cancer is associated with aging, the overall prevalence of cancer will increase as well. With improved availability and tolerability of cancer treatments, more older adults are able to receive treatment and derive benefits, thereby increasing the number of older cancer survivors.^2,3 This group, however, is more vulnerable to short- and long-term treatment-related physical and psychological side effects due to underlying age-related comorbidities, polypharmacy, and both cognitive and physical impairments.^4-8

Increasing emphasis has been placed on assessing and addressing the biopsychosocial needs of older adults.^9,10 The biopsychosocial model stresses the importance of understanding and treating the patient’s illness and assessing physical health and emotional well-being as well as social and environmental factors, many of which are inter-related and may influence one another.¹¹ In the context of cancer and aging, cancer itself and its treatments may lead to functional and cognitive decline or diminished emotional health by contributing to depression and anxiety.^4,12-14 This in turn may result in treatment delay or non-adherence, affecting disease outcomes.¹⁵ Acknowledging the complex needs of older patients, a cancer-specific geriatric assessment tool was developed to uncover these important biopsychosocial needs in older patients.¹⁶ Once these needs have been identified, behavioral interventions such as exercise can be helpful in addressing these needs. For example, exercise may prevent or improve side effects including functional and cognitive decline associated with cancer and cancer treatment, as well as ameliorate psychological and behavioral needs such as depression, anxiety, distress, and low self-esteem. These benefits could lead to improvement in treatment adherence, treatment outcomes, and quality of life (QoL).^17-25 However, exercise is not routinely incorporated into cancer care due to multiple barriers, and studies have shown that less than 50% of physicians recommend exercise in routine clinical care and less than 20% of patients recalled being instructed to exercise by their oncologist.^26-29

In this narrative review, we discuss the common biopsychosocial consequences of cancer and cancer treatment in older patients with cancer. We also review published studies evaluating the effects of exercise on various outcomes and associated challenges faced delivering exercise interventions in this population.

Biopsychosocial consequences of cancer and cancer treatment

Aging is associated with deterioration in multiple organ,³⁰ often accompanied by morbidities, disability and frailty, with a gradual decline in physical fitness and functional reserve.³¹ With a diagnosis of cancer and the addition of cancer treatment, a seemingly fit older individual can decompensate quickly. Many studies have demonstrated that older patients experience a multitude of physical issues as they navigate the management of their cancer, including functional decline, fatigue, bone loss, cardiovascular toxicity, sarcopenia and cachexia.^5,32-37 The prevalence of some of these problems is higher in the older population with cancer than in their younger counterparts and in those of the same age without cancer.^32,34 In a study by Abbema and colleagues, functional status decline at twelve months post-surgery was higher in patients with cancer aged >70 years (43.6%) than in patients with cancer aged 50-69 years (24.6%) and in persons without cancer aged >70 years (28.1%).³⁴ Similarly, in a study by Butt and colleagues, patients with cancer reported more fatigue (36.9%) than those without cancer (46.6%), and fatigue was found to increase with age.³² Detecting and addressing these issues is important, as they are associated with poor outcomes such as increased healthcare utilization and decreased treatment tolerance, QoL, and survival in patients with cancer.^38-41

In addition to physical issues, older patients with cancer experience a variety of psychological and social effects from cancer and cancer treatments including sleep disorders, anxiety, depression, distress, fear, and cognitive impairment.^5,7,42 The prevalence of these symptoms ranged from 10-72% in studies of the geriatric oncology population.^5,7,42,43 Over the last few decades, patients with cancer have described their socio-psychological side effects as severe and long-lasting.⁴⁴ In addition, socio-psychological side effects were perceived to be less tolerable than physical side effects.⁴⁵ They were also associated with poor outcomes including lower performance status, diminished QoL, and decreased survival.^14,46

Exercise recommendations and studies in older adults with cancer

The American College of Sports Medicine (ACSM) recommends that patients with cancer and cancer survivors adhere to the United States Department of Health and Human Services 2008 Physical Activity Guidelines for Americans: 1) Weekly accumulated 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity or an equivalent combination of moderate and vigorous aerobic activity. For older cancer survivors whose physical conditions preclude participation in 150 minutes of moderate-intensity physical activity, they are encouraged to be as active as they are able; 2) Two to three sessions of strength training that engages major muscle groups per week; and 3) Major muscle group stretching on exercise days.⁴⁷ Although this physical activity guideline is generally appropriate for patients with cancer and cancer survivors, 38% of cancer survivors do not adhere to the guideline after the completion of primary cancer treatment.⁴⁸ Among these individuals, almost half are older adults (over 65 years).⁴⁹ Despite the publication of numerous studies showing the benefits of exercise for managing cancer-related toxicities, inclusion of geriatric oncology patients in this research is uncommon.

Table 1 illustrates examples of randomized controlled trials that investigated the effects of exercise intervention (either alone or with another intervention such as diet) on biopsychosocial health in at least 100 patients with cancer with a mean or median age of 60 years or above. The exercise interventions were diverse in terms of mode (e.g. aerobic exercise,^50,51 resistance training,^50-54 the combination of aerobic and resistance training^52,55,56), intensity, frequency, duration, and delivery methods (e.g. home-based exercise program^57,58). These studies demonstrated that exercise improved various biopsychosocial outcomes including physical function, muscle strength, cardiovascular fitness, body composition, weight loss, fatigue, QoL, depression, and cognitive and social function.

Table 1:

Examples of published studies evaluating the effects of exercise in older adults with cancer

Author(s)/Year	N	Age in years, mean/median (range if available)	Sample/Comorbidities if available	Intervention(s)	Control	Outcomes	Positive findings
Bourke, et al. 201452	100	71	Male with prostate cancer who have received at least six months of ADT and will continue to receive ADT 14% were diabetes, 65% were taking cardiovascular medications	Lifestyle intervention consisting of combined supervised and self-directed exercise with dietary advice. Supervised exercise includes 30 min aerobic exercise and two to four sets of resistance exercises targeting large skeletal muscle 2x/week for the initial six weeks and 1x/week for the following six weeks with a total of twelve weeks. Self-directed exercise includes at least one to two twenty min session/week.	Usual care	QoL, fatigue, aerobic exercise tolerance, BMI, blood pressure, PSA, dietary intake	Improved QoL at twelve week but not at six month. Fatigue and aerobic exercise tolerance were improved at twelve week and six month.
Galvao, et al. 201018 and Buffart LM, et al. 201556	100	71.7	Prostate cancer survivors Mean number of comorbidities: 1.5*, 70% had at least one comorbidity; mean number of medication: 1.4	Supervised aerobic (20-30 min of cycling and walking/jogging) and resistance (two to four sets of six to twelve repetitions of eight weight training exercises) exercises for six months followed by a home-based exercise maintenance program (90 min/week) for six months	Printed education material regarding physical activity for 12 months	QoL	Improved aerobic fitness, lower body performance, QoL, physical function and social function
Livingston, et al. 201598	147	65.8	Male with prostate cancer who had completed active treatment within the past three to twelve months	Two supervised gym sessions and one home-based session per week for twelve weeks	Usual care	QoL, anxiety, depression	Borderline intervention effects of depression and cognitive functioning
Morey, et al. 200958 and Demark-Wahnefried, et al. 201257	641	73 (65-91)	Breast, colorectal and prostate cancer survivors Mean number of comorbidities: 2.0	Diet-exercise intervention delivered via mailed print materials and print counseling, fifteen sessions and eight prompts over twelve months (immediate intervention)	Same intervention but was given twelve months later (delayed intervention)	Diet quality, BMI, physical function, QoL	The immediate intervention arm had improved diet quality, physical function and QoL as well as greater weight loss compared to the delayed intervention arm from baseline to one-year follow-up. Both arms had improved diet quality and BMI from baseline to two-year follow-up. Decline in physical function increased in the year after intervention completion in the immediate intervention arm.
Segal, et al. 200353	155	68	Male with prostate cancer scheduled to receive ADT for at least three months	Resistance exercise training consisting of two sets of eight to twelve repetitions of nine strength training exercises 3x/week for twelve weeks	Waiting list control (exercise advice and guidance)	Fatigue, QoL, muscular fitness, body composition	Less interference from fatigue on activities of daily living and higher QoL in the intervention compared to the control group.
Segal, et al. 200950 and Alberga, et al. 201251	121	66.3	Male with prostate cancer receiving radiation with or without ADT 4% were current smokers,	Resistance training consisting of one to two sets of eight to twelve repetitions of ten different exercises vs. aerobic exercise consisting of 3x/week on a cycle ergometer, treadmill, or elliptical trainer for 24 weeks. Intensity of the exercises increases over time.	Usual care	Fatigue, QoL, aerobic fitness, % body fat, muscle strength, cardiovascular fitness, body composition, body weight, serum lipids, PSA, testosterone, hemoglobin	Resistance exercise improved QoL, aerobic fitness, upper- and lower-body strength and triglycerides as well as prevented an increase in body fat. Lean mass was preserved in the resistance training group compared to a decline in the aerobic exercise and usual care group in those >65 years and receiving DVT. Aerobic exercise improved fitness.
Winters-Stone, et al. 201254	106	62.3 (53-83)	Female with early stage breast cancer at least one year post chemotherapy or radiotherapy Mean Charlson Comorbidity Index: 1.7-1.8	Resistance and impact exercise program consisting of one to three sets of eight to twelve repetitions of eight to ten weight training exercises during two one-hour supervised classes and one one-hour home-based session/week for one year	Stretching (whole body stretching and relaxation exercises) placebo program	Maximal muscle strength, grip strength, objective and self-report physical function, fatigue	Improved maximal leg and bench press strength.

^*Cardiovascular disease, hypertension, diabetes, osteoporosis, and dyslipidemia

Abbreviations: %, percentage; ADT, androgen deprivation therapy; BMI, body mass index; Min, minute; QoL, quality of life

Challenges and Research Gaps

1. Identifying the exercise doses and modes for specific outcome

An interesting question is whether various intended outcomes require different exercise doses and modes. In non-cancer populations such as patients with osteoarthritis of the knee, the benefit of aerobic exercise on pain was greater with quadriceps-specific exercises than with lower limb exercise, particularly if performed at least three times a week.⁵⁹ Patient characteristics as well as the intensity and duration of exercise did not affect pain reduction.⁵⁹ In the cancer population, a meta-analysis of 42 trials of adult patients with cancer demonstrates that combined aerobic and resistance training provides the largest treatment effect on cancer-related fatigue. Moderate-intensity aerobic exercise has a greater effect on walking endurance than high-intensity exercise. It is unclear, however, if low-intensity exercise is sufficient to improve outcomes, since studies comparing moderate- and low-intensity exercise are scarce (see Table 1).⁶⁰ One study in patients with breast cancer receiving chemotherapy and/or radiation therapy shows a negative association between exercise intensity and fatigue and QoL.⁶¹ Low- to moderate-intensity resistance training either alone or with aerobic exercise appears to be effective in improving muscle strength, although studies suggest the combination is better.^62,63 On the other hand, the relationships reported between exercise dose and anxiety and depression in the cancer population have been generally inconsistent.^61,64

2. Understanding risks and safety of exercise in older adults

A concern when considering an exercise prescription is the risk of exercise specifically among older adults with cancer. In 2010, ACSM published its exercise guideline in cancer survivors.⁴⁷ The expert panel reviewed over 80 studies and concluded that exercise was safe.⁴⁷ The reported adverse events were uncommon and mild which included pain and musculoskeletal injuries. However, most of the studies were done in patients with breast and prostate cancer and those who underwent hematopoietic stem cell transplantation. In addition, this guideline did not focus on older adults with cancer. As seen in Table 1, information on comorbidity and frailty status of older adults with cancer is frequently not available. Therefore it is unclear if the safety data from existing studies are generalizable particularly to those over age 75 and those with features of frailty who frequently do not meet eligibility criteria for studies. Multiple organizations including World Health Organization, ACSM, and European Association of Cardiovascular Prevention and Rehabilitation state that exercise is generally safe in older adults.^65-67 A systematic review also shows that exercise is safe in frail older adults.⁶⁸ Taken together, although the evidence in older adults with cancer is still lacking, studies in the cancer and general geriatric population suggest that there is a low occurrence of adverse events with exercise. It is important, however, that a pre exercise assessment that includes an evaluation of comorbidities, peripheral neuropathy, musculoskeletal issues, and cardiac conditions is performed in order to tailor the exercise intensity and level for older adults with cancer.^47,66 ACSM also recommends cancer-site specific medical assessments prior to start an exercise program (e.g. evaluation of muscle strength and wasting for prostate cancer, arm/shoulder morbidity prior to upper body exercise for breast cancer, etc).^47,69 Nevertheless, intervention studies designed specifically for older adults particularly those above age 75 and with comorbidity are needed to inform optimal prescriptions and safety data for older adults at various stages in the cancer treatment continuum. Given the heterogeneity in older adults, it is also important for studies to report outcome and safety data by age groups (e.g. 60-69 and over 70).

3. Implementing exercise programs

Despite evidence demonstrating the benefits of exercise, numerous barriers to widespread implementation of exercise programs for cancer survivors exist at the individual, health care team, and organizational levels. Studies have shown that exercise adherence is negatively associated with older age.^70,71 Therefore, it is important to understand age-specific barriers and patient preferences in exercise participation. Some commonly reported individual barriers include: 1) physical barriers such as comorbidities, cancer-related fatigue, pain, and impaired mobility; 2) psychological barriers such as fears and lack of motivation and knowledge; and 3) environmental barriers such as lack of social support, access, and guidance and cost and time constraints.^72-74 At the care team level, barriers include a lack of knowledge of the benefits of exercise, lack of training, and workplace culture. At the organizational level, barriers include a lack of resources and reimbursement.

To overcome exercise adherence at an individual level, understanding exercise preferences and what older patients value is also important. In a prior study of older bladder cancer survivors, participants were more likely to exercise if the program was home-based, light intensity, and unsupervised.⁷⁵ In the general geriatric population, an exercise program is preferred when it is shorter, free, does not require transport, reduces falls, and improves the ability to perform daily tasks at home.⁷⁶ Several studies are ongoing to evaluate the role of novel interventions to promote exercise adherence. With increasing use of technology in daily activities, the incorporation of digital devices into an exercise intervention is attractive. The use of such devices has the potential to enhance exercise self-efficacy and motivation, to serve as a platform for monitoring, and to help address barriers in real-time. In the general geriatric population, adherence rates to technology-based exercise interventions are higher compared to traditional exercise programs, and patients report higher levels of enjoyment.⁷⁷ In the cancer population, adherence rates are not different, although the number of studies is small.⁷⁸ Another novel method is the involvement of a caregiver with the goal of enhancing engagement, and some studies suggest that a dyadic approach may be more effective than individual approach.⁷⁹

At the care team level, oncologists desire a referral process to a cancer-trained physical therapist or trainer.²⁹ Patients are also more likely to adopt exercise if it is recommended by their oncologist.^29,80 These studies highlight the crucial role of oncologists in understanding and encouraging exercise adherence in older patients with cancer and emphasize the need to enhance infrastructure and mobilize resources to assist oncologists in this process. Once patients are referred to exercise professionals, individuals’ health status, treatment received, and disease progression should be considered when exercise is prescribed for this population. To reduce referrals to physicians for medical clearance and barriers to initiating and maintaining a regular exercise program, ACSM updated its recommendations in 2015 to include 1) patient’s currently level of physical activity, 2) presence of symptoms or signs and/or known cardiovascular, metabolic, or renal disease, and 3) desired exercise intensity in the exercise pre-participation health screening.⁸¹ This is different compared to the previous recommendation that is based on cardiovascular risk factor profiling.⁸¹ Although this represents one step further towards increasing exercise participation in older adults, more research is needed on how to disseminate and integrate exercise interventions into routine cancer care.

At the organizational level, several professional organizations such as the National Comprehensive Cancer Network, American Society of Clinical Oncology, and American Cancer Society have established guidelines on physical activity.^82-84 In the United States, many tertiary cancer centers have outpatient cancer rehabilitation programs that include an exercise program. These programs have been shown to improve physical function, QoL, fatigue, symptoms, and psychological health in patients with cancer.^85-89 However, access to these services is limited due to a complicated mix of insurance coverages, copays, and authorization and reimbursement processes. These services may not be fully covered and may specify limited schedules and restrictive guidelines for continuation. Physician attitudes about cancer rehabilitation also lead to decreased utilization.⁹⁰ Healthcare professionals usually do not have a clear understanding of these pathways and referral processes.⁹¹ The multitude of barriers has led to underuse of these services. Some centers have established survivorship programs that include a physical fitness and exercise service. An exercise physiologist is usually available to provide personalized exercise prescriptions and advice. Survivorship programs are generally funded by research grants or by philanthropists and foundations, with little third-party reimbursement. Other centers may have an integrative oncology program that includes exercise counseling.^92-94 However, most of these programs and services are not available in the community setting. Because most patients with cancer are treated by community oncologists, access to exercise programs and exercise physiologists is lacking. In the United States, the YMCA partners with the LIVESTRONG Foundation in many communities to provide adult cancer survivors a twelve-week small group, supervised, circuit style, physical activity program to help alleviate cancer-related side effects, prevent weight gain, and improve energy levels, self-esteem, and quality of life. In addition, the Cancer Support Community and the LIVESTRONG Foundation recently launched the “Cancer Transitions: Moving Beyond Treatment”, a six-week program covering topics of exercise, nutrition, relaxation, stress management, emotional and social support, and long-term medical management for cancer survivors. In Europe, several countries including Denmark, Finland, Sweden, Netherlands, and Germany have established cancer rehabilitations centers. These programs are concentrated in municipalities and include either inpatient or outpatient services or both,⁹⁵ and cover a variety of topics from smoking cessation, dietary advice, physical exercise interventions, and psychological counseling.⁹⁶ Referral to cancer rehabilitation is done by the patient’s oncologist, general practitioner, healthcare professional, or by self-referral.⁹⁶ Cancer rehabilitation in these countries is most commonly covered by government funds, and the interventions are provided by many healthcare professionals: i.e., physiotherapists, nurses, occupational therapists, social workers, psychologists, and certified fitness instructors.⁹² Similarly, these rehabilitation centers are not accessible to patients living in the rural areas and the criteria for referral vary across centers and countries.

Conclusions

With the growing number of older patients with cancer, it is important that we assess and consider their biopsychosocial needs across the cancer continuum. Numerous studies suggest that exercise can address these unmet needs and improve cancer- and treatment-related side effects, but randomized controlled trials in this population are generally lacking. To address research gaps in this field, experts in exercise, aging, and cancer convened at the 2015 Cancer and Aging Research Group and National Cancer Institute U13 conference and published their recommendations in geriatric exercise oncology.⁹⁷

To successfully implement exercise programs in the care of this vulnerable population, there is a need for more research, resources, and education.