Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors

Abstract

Exercise is associated with strong reductions in recurrence and mortality of several common cancers. Cancer survivors who exercise have reduced fatigue, improved quality of life, physical function and body composition. The amount of activity required to achieve protective benefits is moderate, (e.g. walking 30 minutes/day at 2.5 miles per hour). However, many health care providers report a lack of awareness of exercise recommendations, timing and referral to exercise programs for cancer survivors. The American College of Sports Medicine recommends that exercise is safe for cancer survivors and inactivity should be avoided. The guidelines for exercise are 150 minutes of moderate or 75 minutes of vigorous aerobic activity per week, and 2 days a week of resistance exercise. Survivors with lymphedema, peripheral neuropathy, breast reconstruction, central lines and ostomies should follow specific precautions. Providing health professionals with the training and tools needed to provide adequate recommendations to their patients is essential in improving patient outcomes. To facilitate adherence among communities with the greatest need and poor access to services, cultural and environmental adaptation are essential.

PURPOSE AND CONTENT

The purpose of this article is to discuss exercise recommendations for cancer survivors at different stages of survivorship. A survivor is defined from the day of cancer diagnosis to the end of life. This definition is broad and includes people with no tumor burden to those with multi-system failure at the end of life. Clearly, exercise needs to be adapted and individualized for each person along the survivorship trajectory. The article includes a succinct review of the cancer research and a discussion of the American College of Sports Medicine exercise recommendations for cancer survivors.[1] Greater detail focuses on common acute, long-term and late effects of cancer and examine how these side effects impact exercise. The article concludes with a brief discussion of ongoing exercise programs in the community, at cancer centers and culturally tailored programs in specific underserved communities.

Overview of cancer and exercise research

Cancer treatment causes profound debilitation, and leads to reduced physical function and impaired quality of life. These negative sequela have been observed across therapies, from surgery, to radiation to hormonal treatment and targeted therapies.[1] For example, an important indicator of physical fitness and function is aerobic capacity, which has been observed to decrease by 10 to 33% over a 12-week period of chemotherapy for breast and other cancers [3–5] Almost a third of breast cancer survivors have aerobic capacity below what is required for functional independence.[6] Peak oxygen consumption may also be a predictor of survival in metastatic disease.[6]

These declines can be minimized or prevented with a well thought-out progressive program of restorative exercise. A substantial body of evidence demonstrates that exercise is beneficial for a range of objectively measured and self-reported outcomes. Exercise during and following treatment has been associated with reductions in recurrence and mortality, by 30–60% in breast and colorectal cancers,[8–10] and has been found to prevent or reduce many of the negative effects of cancer treatments, such as fatigue, muscle weakness, declines in cardiovascular function, functional ability, neuropathy, body composition and quality of life.[1,3,7,11–20]

These effects are observed across different disease states (e.g. breast, prostate cancer, colorectal cancer, lung cancer, transplant etc.), during and after treatment, and at different stages. For example, the incidence rate of breast-cancer related lymphedema ranges from 6 to 70%. Risk factors include extent of axillary surgery, radiation therapy, and chemotherapy. Breast cancer survivors who engaged in a slow, progressive program of resistance exercise (weight lifting) not only strengthened their affected arm but had a lower incidence and severity of lymphedema.[16] Men with prostate cancer on androgen deprivation therapy face profound changes in skeletal muscle (mass and strength) and body composition. However, prostate cancer survivors on androgen deprivation therapy who exercise gained muscle strength, improved body composition, physical function, quality of life, and reduced fatigue.[17–20]

The amount of physical activity required to achieve many of the protective benefits of exercise is moderate.[8] Walking 30 minutes five-days a week at about 2.5 miles per hour conveys beneficial effects and is attainable for most cancer survivors.[8] During a period of time when we expect patients to become debilitated, simple exercises like walking 3 or 4 days a week can prevent the typical declines and for many improve their functional ability. It is time we change our thinking about caring for cancer survivors and become proactive advocates for restorative exercise during and following treatment.

Despite a rapidly growing body of knowledge about the benefits of exercise for cancer survivors, 80% of oncology care providers (nurses and physicians) are unaware of the exercise guidelines and report a lack of knowledge about them, when to implement them and where to refer survivors for exercise.[2] As a result, few survivors receive formal information about exercise, a referral or even direction to a community-based cancer survivor exercise program. Notably, oncology care providers who themselves are physically active and meet the national exercise guidelines are significantly more likely to discuss exercise with their patients and provide a referral.[2]

To provide optimal care during and following treatment, survivors should be referred for restorative exercise to reduce fatigue, weakness, risk for lymphedema, pain, and improve functional ability. Where one refers a survivor may be based on the individual survivors’ level of function, previous experience with exercise and their degree of debilitation and comorbidities. Initially, survivors with severe debilitation and other comorbidities that greatly limit function may achieve the greatest benefit by working with a physical therapist. Survivors who are functionally able without any specific deficit (s) (e.g. lymphedema, peripheral neuropathy, pain, muscle weakness) other than the negative effects of cancer treatment will benefit from a community-based program that is directed by a cancer exercise specialist, such as LIVESTRONG at the YMCA.[21]

ACSM Guidelines exercise guidelines for cancer survivors

In 2009 the American College of Sports Medicine (ACSM) convened a multidisciplinary group of experts to review cancer exercise research and develop guidelines for survivors.[1,7] In many ways the ACSM Exercise Guidelines for Cancer Survivors mirror the US Physical Activity Guidelines, but specific recommendations are given for different sites of cancer, stages of disease, types of treatment and acute, long-term and late treatment effects. The overwhelming message to convey to all cancer survivors is to avoid inactivity and that any physical activity may provide some health benefit.

The ACSM guidelines for cancer survivors recommend that all cancer survivors attain at least 150 minutes of moderate or 75 minutes of vigorous aerobic activity per week and 2 days a week of resistance exercise at a moderate to high intensity for all major muscle groups.[1] Flexibility exercises are recommended for all major muscle groups too. Exercises to improve balance are recommended for older adults and there is little downside to including them in a survivor regimen at any age, especially if the survivor has problems with balance. Explicit recommendations are made for cancer-specific conditions, such as: lymphedema, peripheral neuropathy, breast reconstruction, central lines and colorectal survivors with ostomies who should avoid excess abdominal pressure. While the research to date has limitations to generalizability and does not include all cancer populations, the overall findings are strong enough to recommend that exercise is safe, should be encouraged and to avoid inactivity.

Specific side effect issues

Acute Effects of treatment

Acute treatment-related side effects occur during active treatment when survivors are often immune compromised and are learning to cope with side effects, such as, nausea, vomiting, fatigue, skin rashes, peripheral neuropathy, hair loss, pain, anxiety, depression and changes in self-esteem and body image. These acute treatment-related side effects have a negative impact on quality of life and contribute to the declines in physical and emotional function.

Exercise is possible during active treatment, but survivors need to learn to manage their side effects before they escalate from mild to severe. An exercise program needs to be adapted to the individual’s abilities and focus on improving their specific physical limitations. Many studies have demonstrated that during active treatment exercise improves fatigue, weakness, nausea, depression, anxiety and quality of life.[1,7,12,15,16, 22–25]

Oncology professionals need to help patients manage their side effects so they can exercise and function at the highest level possible. Exercise professionals may need to guide the survivor to learn to adapt exercise to their physical state, side effects and degree of fatigue to optimize performance outcomes.

Long-Term Effects of Treatment

Long-term effects of cancer treatment are side effects that begin during treatment and linger many months or years after treatment. Examples are lymphedema, fatigue, peripheral neuropathy, infertility, pre-mature menopause and changes in body composition. Long-term effects often necessitate adapting an individualized restorative exercise program to minimize risk for injury or lymphedema. The goal is to adapt exercise and still give the survivor the optimal benefits from exercise. For example, lymphedema does not preclude exercise, but exercise precautions must be observed to avoid a flare-up and still increase muscle strength and range of motion. Gradual, progressive resistance exercise is safe and recommended to reduce the risk and severity of lymphedema.[15,16,26] Another important recommendation is the use of compression garments (e.g. sleeve and/or glove) when exercising.

Cancer-related fatigue continues to be a chronic and persistent problem for approximately 33% of long-term breast cancer survivors.[27–29] Fatigue is exacerbated by other symptoms. Fatigue levels increase with neuropathy, with Raynaud-like symptoms and with anxiety and depression. Rest and a sedentary lifestyle compound fatigue by accelerating debilitation. Evidence demonstrates that physical activity reduces fatigue.[1, 13,14, 17,18, 24, 30] Developing an exercise program for long-term cancer survivors with fatigue must begin and progress slowly. Survivors may initially be shocked by their degree of debilitation but quickly see gains in muscle strength and cardiovascular endurance.

Peripheral neuropathy is a side effect of many chemotherapy agents that plagues a staggering 60% of patients up to 3 months post-treatment and does not appear to improve over time for up to 30% by 6 months post-treatment and beyond.[31] Some preliminary studies suggest that exercise may improve peripheral neuropathy, although no interventions have been discovered that reverse or prevent the neurologic damage.[25] When long-term cancer survivors begin exercise, balance may be impaired due to peripheral neuropathy and general weakness. It is important to tailor an exercise prescription to not only improve muscle strength and aerobic capacity, but also improve and restore balance. Referral to physical therapy or a community-based exercise program should focus on core and pelvic girdle strength. An easy exercise that one could do at home is to balance on one foot, while holding onto something stable nearby. Improving balance not only reduces fall and fracture risk, but also builds movement confidence.

Cardiopulmonary complications of cancer treatment can emerge during active treatment but generally become problematic at later stages of survivorship for a wide range of different cancers, including breast, Non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and testicular cancer.[32,33] Heart failure is an early sign that may occur during some chemotherapy (e.g. trastuzumab, doxirubicin) and may present years later. Other cardiac complications include hypertension, arrhythmia, arterial stenosis, conduction disorders and valvular disease. Pulmonary effects from chemotherapy and/or radiation therapy may include radiation pnuemonitis, pulmonary fibrosis and a reduction in pulmonary function. Breast cancer survivors demonstrate such severe declines in cardiac function that they actually have accelerated aging.[6] Fortunately, these cardiac declines can be largely reversed with physical activity.[6]

Ongoing research is examining the hypothesis that structured exercise in testicular cancer may prevent cardiovascular disease.[34] While more research is needed to determine optimal dose, duration and timing, evidence is growing to support the notion that progressive restorative exercise programs may not only reverse, but also mitigate some cancer treatment-related cardiopulmonary complications.

Late-effects of treatment

Late effects of cancer treatment develop years after treatment has ended and may impair functional ability and exercise. Osteoporosis and cardiovascular disease [14,32,35] are two common examples of late effects of the chemotherapy and hormonal therapies that cause bone wasting, leading to osteopenia and osteoporosis.

The late cardiac effects of cancer treatment have a profound effect on survivors who have as much as a 70% higher risk for developing cardiovascular disease compared to someone without cancer.[6,32,34] The most common conditions are myocardial dysfunction and heart failure, coronary artery disease, valvular disease, arrhythmias, arterial hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension and pericardial problems. Common classes of chemotherapy drugs that can cause left ventricular dysfunction include: anthracyclines, alkaylating agents, antimetabolites, antimicrotubule agents, monoclonal antibodies and small molecule tyrosine kinase inhibitors. Radiation therapy alone or concurrently with a cardiotoxic chemotherapy can predispose a survivor to interstitial myocardial fibrosis, diastolic dysfunction, and heart failure. In patients treated with mantle field radiation, these cardiac effects are often not seen for 15–20 years after treatment. Hodgkins lymphoma survivors who have received mantle field radiation and cardiotoxic drugs have a two to seven-fold increased risk of myocardial infarction.[36–38]

Cardiovascular disease is the leading cause of mortality for women with early stage breast cancer.[39,40] These women are also at an increased risk for coronary artery disease and heart-failure.[39,40] Exercise may have potential benefits to modulate cardiovascular disease among early-stage breast cancer survivors.[40] A longitudinal prospective study of almost 3,000 women with nonmetastatic breast cancer noted that women who adhered to the cancer survivor exercise guidelines (vs. those who did not) had a 23% adjusted reduced risk of cardiovascular events.[40]

Cancer Survivor exercise programs

With a growing body of research in exercise oncology, so are community programs. Many physical and occupational therapists offer restorative cancer exercise programs, which are fully reimbursable by insurance for indications such as fatigue, muscle weakness, muscle spasms, osteoporosis, pain, connective tissue disorders (scars and fibrosis), cardiopulomonary conditions, and lymphedema. These programs may focus on improving overall function or specifically on managing or preventing lymphedema, improving functional ability, weakness and range of motion. LIVESTRONG at the YMCA is a community-based exercise program that is led by ACSM certified Cancer Exercise Trainers.[21] These individuals have received formal training to work with cancer survivors during and following cancer treatment and understand how to structure and adapt exercise for survivors with different diagnoses, types of treatment and stages of disease. There are many other community programs that are more loosely structured. Online programs, such as Restwise™ help survivors learn to interpret their symptoms and understand when to rest and how hard to exercise in order to maximize benefits.[41]

It is particularly important to focus cancer exercise interventions on vulnerable populations with traditionally poorer access to care, as research has consistently demonstrated poorer screening rates and lower survival rates. For example, compared to White populations, African American men and women have a 37% and 17% higher death rate and lower 5-year survival for almost all cancers.[42] Native American populations have the lowest 5-year survival rates of any population (59.0%), and were the only group that did not see reductions in cancer mortality from 2001 to 2010.[42]

To reach these populations, adaptation of programs that have demonstrated efficacy is needed. To date, most culturally adapted programs target education and screening, not survivorship. [43–45] An example of a physical activity intervention for Native American populations is a project called “Restoring Balance.” This program is a cancer survivor exercise program developed specifically for Native Americans. The program follows the ACSM Exercise Guidelines for Cancer Survivors and is culturally tailored to meet the specific needs and preferences of Native American cancer survivors.[46] An important piece of tailoring the intervention was to ensure that the individuals working with survivors had specialized training in working with Native populations. They understood the cultural nuances around discussing cancer and treatment, common barriers, environmental circumstances and the historical context of the population. For example, accessibility of facilities may require flexibility in scheduling and a combination of face-to-face and home-based exercise. In addition, all activities and materials were vetted to ensure alignment with traditional cultural preferences and feasibility in the environment.[46]

What clinicians can do now

Provide clear succinct information about exercise at every visit and emphasize that inactivity should be avoided. Survivors need to know that exercise is safe and beneficial at all stages of survivorship, but it needs to be stressed that exercise should begin slowly with a gradual progression to increase volume (time) and intensity. Survivors with specific limitations should be referred to physical or occupational therapy, and survivors who have fewer limitations should be directed to community-based programs. It is important to remind survivors to start slowly and progress slowly. A simple handout with ACSM exercise recommendations will make educating the survivor simple and time efficient.

Conclusions

Ideally, restorative exercise should begin as soon as possible after diagnosis to enable the survivor to obtain optimal benefits and improved tolerance for treatment, and reap the physical and emotional benefits.[1,4] However, it is never too late to refer a survivor to an exercise program. Exercise at any point in the survivorship trajectory helps survivors maintain and improve functional ability, body composition and quality of life to be able to pursue a full and meaningful life.

Table 1.

ACSM Exercise Guidelines for Cancer Survivors

• 150 minutes/week of moderate intensity physical activity or 75 minutes of vigorous physical activity

• Strength training (resistance) exercise 2 or more days per week involving all major muscle groups.

• Adapt exercise to individual’s ability with thought to:

○ surgical effects (e.g. lymphedema, decreased range of motion, pain),

○ chemotherapy/immunotherapy or radiation side effects (e.g. immune compromise, fatigue, peripheral neuropathy, weakness)

• Some exercise is better than none.

• The benefits of exercise outweigh the risks.

• Refer to physical or occupational therapy, community or home-based programs.

Table 2.

Goals of Exercise for Cancer Survivors

• Avoid inactivity

• Restore and improve physical function, aerobic capacity, strength and flexibility

• Improve function: cardiorespiratory, endocrine, neurological, muscular, cognitive and psychosocial.

• Improve quality of life and body image

• Improve treatment tolerance

• Reduce risk of recurrence and development of other cancers

• Prevent or mitigate long-term and late effects of treatment

• Improve ability to cope with current treatment or future cancer treatments.

KEY POINTS:

• Cancer Survivors should avoid inactivity.

• Exercise is safe and beneficial for cancer survivors at all stages of survivorship.

• Exercise should be adapted to acute, long term and late effects impacting the survivor.

• To provide optimal care during and following treatment, survivors should be referred for restorative exercise.