Clare Stevinson Kristin L Campbell Christopher M Sellar and Kerry S Courneya

1.0. INTRODUCTION

Interest in the potential of exercise as a therapeutic intervention for a wide range of clinical populations is growing steadily. A body of research has established physical activity as having a role in the prevention and/or management of several chronic medical conditions,1 including coronary heart disease,2 stroke,3 hypertension,4 non-insulin-dependent diabetes,5 obesity,6 musculoskeletal disorders,7 and mental health problems.8

Evidence of the effects of physical exercise in protecting against cancer has been emerging since the 1960s. More recently research attention has turned to the potential benefits of exercise for individuals already diagnosed with cancer. This chapter summarizes the evidence available so far in this area, and outlines the new directions being taken to advance understanding of the value of physical activity across the cancer spectrum: from prevention, through detection, treatment, and palliation, toward long-term survivorship.

2.0. HEALTH CHALLENGES FOR CANCER SURVIVORS

The challenges to health and well-being faced by cancer survivors can be quite diverse depending on the site and stage of cancer, as well as characteristics such as age and gender. In addition to the effects of the disease, receiving a diagnosis of cancer and undergoing cancer therapy can result in a range of negative side effects that diminish quality of life. Common physical consequences of surgery and adjuvant therapy include impaired cardiopulmonary function, deterioration in lean body tissue and muscular strength, and decreased range of motion.9 These can all impact on the ability to carry out activities of daily living (e.g., dressing, housework, childcare, shopping, gardening), occupational work, and social activities, and can be further compounded by fatigue. Cancer-related fatigue is characterized by complete lack of energy and severe mental exhaustion, and is one of the most common and most distressing symptoms reported.10

Alterations in body weight and body composition affect many cancer survivors. Weight loss is a typical symptom of many cancers, and both chemotherapy and radiotherapy can cause mucositis, anorexia, and nausea, making food intake difficult.11 Conversely, weight gain is associated with some chemotherapy protocols used in treating breast cancer,12 and increased appetite caused by some steroid treatments. Reduced activity during and after cancer treatment also contributes to weight gain. Further side effects include pain, sleep disturbances, cognitive impairments (e.g., forgetfulness, inability to concentrate),13 and a host of psychological sequelae.14 These can range from clinical depressive or anxiety disorders, to occasional feelings of anger, guilt, confusion or loneliness. Loss of self-esteem, and concerns over body image, are also frequently reported. Psychological distress may persist long beyond the end of treatment in some cancer survivors,15,16 and can have a significant impact on the ability of some individuals to return to work.17

3.0. HEALTH-RELATED EFFECTS OF EXERCISE

Exercise has a range of physiological effects, many of which are potentially beneficial for cancer survivors at the time of treatment and afterwards. Some of the likely benefits of regular physical activity for cancer survivors are related to improvements in health-related fitness components. These are particularly relevant to the ability of individuals to carry out activities of daily living, and are associated with a lower risk of diseases linked to a sedentary lifestyle.18 The components of health-related fitness are cardiorespiratory fitness, muscular fitness, body composition, and flexibility.18

Cardiorespiratory fitness refers to the ability to maintain a level of physical activity for a continuous period of time and involves the cardiovascular, respiratory, and musculoskeletal systems of the body.18 Cardiorespiratory fitness has been shown to be a strong predictor of mortality in both healthy individuals and those with a chronic illness.19 This type of fitness is developed through aerobic exercise, consisting of repetitive, continuous movement of the body's large muscle groups (e.g., walking, jogging, cycling, swimming).20 Aerobic exercise training is associated with improvements in a wide range of outcomes: cardiovascular and respiratory function, exercise capacity and endurance, resting heart rate, blood pressure, glucose tolerance and lipid profile, body composition, functional abilities and work, recreational, and sport performance, psychological well-being, depression, and anxiety. Through these effects, cardiorespiratory fitness is effective in preventing, and/or managing, a number of chronic illnesses.18,21,22

Muscular fitness can be subdivided into strength and endurance components. Muscular strength is the ability of a specific muscle (or group of muscles) to generate force (also referred to as maximum voluntary contraction or MVC), while muscular endurance is the ability of the muscle to complete a repeated number of contractions over time.18 Recent evidence suggests that muscular fitness, independent of aerobic exercise, is associated with mortality.23 Resistance training is the primary mode of improving both muscular strength and endurance. Benefits of resistance training include improvements in: bone mass/density, glucose tolerance, resting metabolic rate, fat-free mass, exercise capacity, postural stability and balance, and performance of activities of daily living.18

Body composition refers to the relative percentages of fat mass and fat-free mass that make up the body.18 Specific measurements of body composition provide better estimates of body fat than do those based simply on weight, height, and/or circumferences.18 Individuals with large amounts of body fat are at greater risk of developing various chronic illnesses.6 Improvements in body composition can be achieved through both aerobic exercise and resistance training, and may act through increases in total caloric expenditure, fat-free (lean) body mass, and resting metabolic rate.6 These favorable changes to body composition can result in decreased risk of numerous medical conditions including some cancers.6

Flexibility is defined as the ability of ajoint (or joints) to move through a complete range of motion (ROM) and plays an important role in the ability to perform activities of daily living.18 The performance of regular stretching exercises specific to eachjoint is required to maintain or improve flexibility.18 This may improve joint ROM and function, and enhance muscular performance resulting in improved functional abilities.20 Furthermore, regular flexibility training may play a role in reducing the incidence of, and treating, musculoskeletal injuries.20

4.0. EVIDENCE FOR PREVENTION AND SURVIVAL OUTCOMES

The evidence that physical activity can prevent cancer has been accumulating since a seminal study of railway workers in 1962 that demonstrated a 30% reduced risk in cancer mortality among section men compared with clerks.24 There are currently more than 180 epidemiological studies investigating the association between physical activity and cancer risk. Evidence for risk reduction attributable to physical activity is considered "convincing" for colon and female breast cancer, "probable" for endometrial cancer, and "possible" for prostate and lung cancer. Lower risk at other cancer sites (i.e., testicular, ovarian, kidney, pancreas) has also been reported, but the evidence is "insufficient" at this time due to the small number of studies.25,26

The biological mechanisms behind the apparent protective effects of physical activity have not been established, but several systemic and site-specific mechanisms have been suggested.25 Systemic effects of physical activity include the modification of metabolic hormones and growth factors, improvements to the antitumor immune defence system, and regulation of energy balance and fat distribution. Physical activity may also promote antioxidant defence and DNA repair. Additional site-specific mechanisms include alterations in levels of sex steroid hormones (e.g., estrogens, progesterone, and androgens) that are implicated in hormone-dependent cancers such as breast, endometrial, ovarian, and prostate. In the case of colon cancer, decreased gastrointestinal transit time may reduce exposure to carcinogenic agents, and changes to levels of insulin, prostaglandin, and bile acids may inhibit colonic cell proliferation. Improved pulmonary ventilation and perfusion may help to prevent lung cancer through minimizing the presence of carcinogens in the airways.

Although there are currently insufficient empirical data to establish the precise mechanisms for the anticarcinogenic effects of physical activity,27 it is an area of considerable research activity. Furthermore, it is feasible that some of the mechanisms thought to be responsible for the role of exercise in the primary prevention of some cancers, may also confer benefits in terms of secondary prevention outcomes such as disease recurrence and survival.

4.1. Cancer Mortality and Recurrence

There is limited research on the effect of physical activity on disease recurrence and mortality in cancer survivors, with data available from four studies so far. In a randomized trial of group psychotherapy in 66 metastatic breast cancer survivors, self-reported regular exercise was the only nonmedical variable to predict survival.28 In a recent cohort study, the amount of self-reported leisure-time physical activity was assessed in 41,528 Australians, among whom 526 cases of colorectal cancer were identified.29 Those who reported regular exercise (at least once a week) prior to diagnosis, had improved cancer-specific survival (73% 5-year survival) compared with those not reporting regular exercise (61% 5-year survival). In addition, cancer-specific mortality was higher in those with higher body weight, percent body fat, and waist circumference: all factors that can be positively influenced by physical activity. The observed association between exercise and cancer-specific mortality was also influenced by cancer stage and site. A greater risk reduction was observed for those with stage II and III compared with stage I and IV cancers, and in those whose cancer originated in the right colon, rather than the left colon or rectum. Recurrence was not assessed in this study. Another study involving 816 patients with stage III colon cancer, observed increases in recurrence-free survival, disease-free survival, and overall survival in association with increasing volumes of physical activity.30 After controlling for various demographic and medical variables, those performing at least 18 MET-hours of exercise per week (equivalent to 1 hour of brisk walking 6 days per week) had a 49% reduction in risk of recurrence or death compared with those performing <3 MET-hours per week over a 3-year period following surgery and chemotherapy.

Using data from the Nurses Health Study, the amount of self-reported leisure-time physical activity was assessed in 2987 female breast cancer survivors after diagnosis.31 Women who reported at least 3 MET-hours of physical activity (equivalent to 1 hour of walking) per week or more, had a decreased risk of recurrence or cancer-specific mortality compared with women who reported less physical activity. A further reduction in risk of recurrence and cancer-specific mortality was seen with higher levels of physical activity, up to 23.9 MET-hours per week. Overall, 5-year survival was 93% for <3 MET-hours per week, 97% for 3-8.9 MET-hours per week, and 97% for >9 MET-hours per week. The corresponding rates for 10-year survival were 86%, 89%, and 92%. In addition, this risk reduction held for normal weight (BMI <25), overweight (BMI 25-30), and obese (BMI >30) women who engaged in 9 or more MET-hours per week. However, the benefits of physical activity (<9 versus >9 MET-hours per week) appeared to be limited to women with hormone-responsive tumors. This finding was based on small numbers of deaths so further research is required to determine the impact of tumor characteristics on the relationship between physical activity and cancer recurrence and cancer-specific mortality. Further data on the effects of exercise on cancer recurrence is currently being collected from a cohort of over 1200 breast cancer survivors and 1000 prostate cancer survivors who participated in case-control studies.32,33

4.2. Cancer Biomarkers

Studies assessing recurrence and mortality obviously take many years to perform. Other studies are focused on the shorter-term effects of physical activity on intermediate biological markers that are thought to lie on the causal pathway between exercise and cancer recurrence or mortality. These trials provide important data on the potential mechanisms by which exercise may influence disease progression and survival.

4.2.1. Sex Steroid Hormones

Cumulative lifetime exposure to sex steroids, particularly estrogens has been linked to breast, endometrial, and ovarian cancer, while androgen exposure has been linked to prostate cancer. Physical activity has been shown to lower estrogen levels in premenopausal women through a continuum of alterations in menstrual cycle function.34 Furthermore, for postmenopausal women, exercise leads to reductions in body fat, and increases in sex hormone binding globulin concentration, resulting in less bio-available estrogens and androgens in both men and women.25

The effects of a 12-month aerobic exercise intervention were examined in 173 sedentary, overweight, postmenopausal women without cancer.35 The exercise group had a significant decrease in estrone, estradiol, and free estradiol compared to no change or increase in the control group at 3 months. These differences were maintained at 12 months, but were no longer statistically significant. A similar nonsignificant decrease in androgens was noted in both groups. However, those who lost weight had a significant decrease in testosterone and free testosterone, which was greater in the exercise group than the control group despite similar weight loss. To date, the effect of physical activity on sex steroid hormones in cancer survivors has only been examined in a small pilot study of nine breast cancer survivors who engaged in an 8-week physical activity (3 times per week of aerobic activity) and low fat diet (20% calories from fat) intervention.36 Slight, nonsignificant decreases were observed in serum concentration of total and free estradiol, estrone sulfate, total testosterone, androstenedione, and dehydroepiandrosterone.

4.2.2. Body Composition

Higher body weight is associated with increased risk of colon, kidney, esophageal, endometrial, thyroid, and postmenopausal breast cancer.37 In addition, abdominal fat is proposed to result in higher cancer risk than overall body fat.38 Physical activity and reduced dietary intake can decrease body weight, while physical activity may preferentially reduce intra-abdominal fat38 and is associated with improved weight maintenance after weight loss.25

In randomized controlled trials of physical activity in breast cancer survivors, a 12-month resistance intervention in 85 women resulted in a significant increase in lean body mass and significant decrease in percent body fat, with no change in overall body weight, BMI, or waist circumference,39 while a 15-week aerobic activity intervention in 52 women did not result in a change in body weight, BMI, or sum of skinfolds.40 In a trial of a 3-month aerobic intervention in 123 women, no overall change in body weight between the supervised exercise group, home-base exercise group, and control group was recorded.41 However, when type of cancer treatment was considered, in those not receiving chemotherapy, the supervised exercise group lost body weight while there was a slight increase in both the home-based and control groups. In a randomized controlled trial of physical activity in 155 prostate cancer survivors undergoing androgen deprivation therapy, no change in body weight, BMI, waist circumference or sum of skin folds was noted.42

4.2.3. Metabolic Hormones

Higher insulin and IGF-1 levels have been associated with increased cancer risk.25 Physical activity decreases insulin and increases IGFBP-3, which binds IGF-1 limiting its bioavailability, while the evidence for changes in IGF-1 is mixed.25

In 443 colorectal cancer survivors who reported leisure time physical activity prior to diagnosis, no difference in IGF-1 or IGFBP-3 was observed by activity level and no association with cancer-specific mortality existed.43 However, in the physically active group, those in the highest quartile of IGFBP-3 had a significant decrease in cancer-specific and all-cause mortality. No association was demonstrated for the inactive group. In the randomized controlled trials with breast cancer survivors described above, the 12-month resistance program resulted in a significant decrease in IGF-II but no change in fasting glucose, insulin, insulin resistance, IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3,39 while the 15-week aerobic exercise program resulted in a decrease in IGF-1 and increase in IGFBP-3, with no change in fasting glucose, insulin, insulin resistance, IGF-II, IGFBP-1, or IGFBP-2.44

4.2.4. Immune Function and Inflammatory Markers

An improvement in antitumor immune defences could potentially impact all cancer sites.25 Physical activity has been shown to increase the number and activity of macrophages, as well as lymphocyte activity and proliferation.25 Furthermore, physical activity may reduce systemic inflammation45 which has been linked to numerous chronic health conditions, including cancer.46

In the randomized controlled trial in 52 breast cancer survivors previously described, a 15-week aerobic exercise intervention resulted in an increase in natural killer cell cytotoxic activity and unstimulated [H3]thymidine uptake by peripheral lymphocytes.44 Furthermore, there was a nonsignificant decrease in high-sensitive c-reactive protein, a marker of inflammation that has been linked to cardiovascular disease.47 A trial of 35 stomach cancer patients undergoing surgery also reported increased natural killer cell cytotoxic activity.48 Positive correlations between natural killer cell function and both recurrence and cancer-specific mortality have been suggested.49

Overall, there has been limited research on the effects of physical activity on proposed biomarkers of cancer recurrence, cancer-specific mortality, or all-cause mortality. Thus far, compelling evidence for the mechanisms through which physical activity may influence secondary prevention in cancer does not exist. However, research efforts are continuing in the attempt to validate biomarkers and understand the effects of exercise on these intermediate outcomes, with the ultimate aim of increasing disease-free intervals and overall survival.

5.0. EVIDENCE FOR REHABILITATIVE OUTCOMES

Although there is increasing interest in investigating the potential effects of exercise on disease and survival outcomes, the majority of research on exercise for cancer survivors so far has been directed at outcomes relating to treatment management and rehabilitation.

Since the pioneering work of Maryl Winningham of Ohio State University College of Nursing during the 1980s,50-52 the volume of research in this area has grown exponentially. By the close of the 20th century, more than 60 journal articles

Table 1. Recent Systematic Reviews of Exercise for Cancer Survivors

Authors

Review

Reviewer conclusions

Conn et ai54

McNeeleyei al.'6

Schmitz et alf1

Knols et al.6

Douglas5

Galvao and

Newton'

Stevinson etal.

Oldervoll etal.64

Systematic review of 30 intervention trials with meta-analysis Systematic review of 14 randomized breast cancer trials with meta-analysis

Systematic review of 32 controlled trials with meta-analysis

Systematic review of 34

controlled trials Systematic review of 21 intervention studies

Systematic review of 26 intervention studies

Systematic review of 33 controlled trials with meta-analysis

Systematic review of 12

randomized controlled trials

Exercise interventions resulted in small positive effects on health and well-being outcomes among existing studies.

Preliminary evidence suggests that exercise is an effective intervention to improve quality of life, cardiorespiratory fitness, physical functioning, and fatigue.

Physical activity improves cardiorespiratory fitness during and after cancer treatment, symptoms and physiologic effects during treatment, and vigor posttreatment.

Cancer patients may benefit from physical exercise both during and after treatment.

There is a growing body of evidence to justify the inclusion of exercise programs in the rehabilitation of cancer patients returning to health after treatment.

Preliminary positive physiological and psychological benefits from exercise when undertaken during or after traditional cancer treatment.

Exercise interventions for cancer patients can lead to moderate increases in physical function and are not associated with increased symptoms of fatigue.

Cancer patients benefit from maintaining physical activity balanced with efficient rest periods.

or theses had been written on exercise after cancer diagnosis, and half a decade later, the body of evidence now comprises well over 200 reports. Furthermore, the geographic spread of research activity has widened considerably over this time and includes studies conducted in at least 15 different countries across six continents.

A number of review articles have been published that attempt to summarize the results and implications of individual studies.53-72 Conclusions from reviews have been consistently positive with regard to the potential benefits of exercise during cancer therapy and after treatment completion. Table 1 summarizes the conclusions of recent systematic reviews that have evaluated the evidence.

5.1. Physical Function

The most consistent and positive effects demonstrated in randomized clinical trials relate to physical function outcomes. Results of meta-analyses show moderate improvements in cardiorespiratory fitness among cancer survivors engaging in aerobic exercise programs during, and after, cancer treatment.54,62,67,70 The benefits of preserving fitness during treatment, and gradually increasing it again afterwards, are considerable in terms of being able to perform daily activities and continuing with leisure pursuits.

Similarly encouraging functional outcomes have been demonstrated in trials that have focused on resistance exercise training. Reductions in shoulder pain and disability were reported in head and neck cancer survivors who had undergone spinal accessory neuropraxia/neurectomy,73 and increases in muscular fitness42 and muscle mass74 have been found for prostate cancer survivors receiving androgen deprivation therapy. Increased muscle mass was also demonstrated in breast cancer survivors following a 6-month weight training program.39 If resistance exercise helps to prevent or reverse the loss of muscle tissue that can result from inactivity, inadequate nutrition, or cachectic processes, it would make a significant contribution to cancer survivors' functional abilities.

5.2. Treatment Side-Effects

There is some preliminary evidence that exercise can help in the management of treatment-related symptoms or side effects.67 A serendipitous finding of one of the early trials by Winningham and MacVicar was reduced nausea following exercise in breast cancer survivors on chemotherapy.51 A subsequent trial found that more participants reported reduced nausea in the exercise group, compared with the control participants.75 Other trials have found fewer sleep problems reported by breast cancer survivors undertaking walking programs during chemotherapy76 and radiation treatment,77 than those receiving usual care. Another trial involving inpatients receiving high-dose chemotherapy following peripheral blood stem cell transplantations demonstrated a range of positive outcomes for those exercising daily on a supine cycle ergometer, compared with control participants.78 These outcomes included lower pain severity and less use of analgesics, lower severity of diarrhea, shorter duration of thrombopenia and neutropenia, and shorter hospitalizations.

Cancer-related fatigue has been identified as one of the most common and distressing symptoms reported by patients, and also one of the most difficult to treat.10 An overemphasis on rest carries the likelihood of causing increased fatigue, due to individuals becoming caught in a vicious cycle of inactivity that leads to further de-conditioning, hence greater fatigue upon even minimal exertion. Some trials have reported reductions in fatigue in participants exercising during treatment,42,76,77 and those who have completed treatment.40,79 However, not all trials have demonstrated this effect, and the results of meta-analyses are conflicting on this outcome, with no significant change in fatigue found in three reviews,54,67,70 but a small significant reduction in another.62 It is important to note that there is little evidence of increased fatigue from exercise. This is a highly positive finding with respect to the understandable concerns of patients and caregivers that exercise may cause or exacerbate existing fatigue. Instead, current evidence suggests that by adhering to a graded exercise program, cancer survivors can maintain or increase their level of conditioning and function, thereby avoiding becoming trapped in a perpetuating cycle of deteriorating physical function and increasing fatigue.

Exercise has been suggested as useful method of reversing unwanted weight gain in cancer survivors.80 Although, some studies have reported improved body composition (i.e., increases in lean/fat tissue ratio)39,74,79,81-83 there is no evidence of significant changes in total body weight.67,70 It may be that most clinical trials of exercise have been of insufficient duration to affect body weight, and that this outcome is better addressed in longer-term health promotion protocols. A recent systematic review of trials in breast cancer survivors, concluded that the evidence for improved body composition was sketchy, but encouraging.84

5.3. Quality of Life

Many trials have measured the effect of exercise interventions on quality of life or psychological well-being in cancer survivors. Some promising results have been reported for breast cancer patients both during and posttreatment for overall quality of life,40,85 anxiety,77,86 depression,41,76,86 body image,76,77 and self-esteem.40,87

Quality of life was also enhanced in two prostate cancer trials.42,74 However, other trials have been published which found no difference between exercise and control groups in measures of quality of life and psychological distress.88-90 and the results of meta-analyses have also been conflicting for these outcomes.62,67

6.0. RISKS OF EXERCISE

Clearly, for exercise to be considered a valuable intervention that can be routinely recommended to cancer survivors, it must have a positive risk-benefit ratio. The risks associated with exercise at levels required for health promotion, are low in the general population. For cancer survivors, concerns relate to the possibility of exercise leading to immunosuppression, falls, bone fractures, complications of car-diotoxic treatments, exacerbation of pain and other symptoms, and interference with treatment completion or efficacy.

Systematic reviews of trials with cancer survivors have reported few adverse events associated with exercise. However, it should be noted that clinical trials have rigorous screening criteria and exclude participants for whom exercise may pose a potential risk (e.g., those with uncontrolled cardiovascular or pulmonary disease, existing musculoskeletal disorders, or cancer-related conditions such as severe cachexia, anemia, neutropenia, thrombocytopaenia, or metastatic bone disease). Studies that have addressed the role ofexercise in causing or worsening lymphedema in breast cancer survivors who have undergone axillary node dissection, have found no increased risk with upper body physical training.91-93

In assessing the risk-benefit ratio of exercise, it is important to consider the potential harm to cancer survivors of remaining inactive, alongside the possible hazards of exercise. Physical inactivity leads to deconditioning, bone loss, and muscle atrophy, decreases in glucose metabolism, insulin sensitivity, digestive function and immunosurveillence, and increases in cardiovascular risk factors (e.g., lipid levels, blood pressure). Maintaining regular activity is essential therefore for reducing the risk of developing other chronic conditions (e.g., diabetes, cardiovascular disease, osteoporosis), and particularly so for cancer survivors who may at increased risk of further disease.94-96

7.0. SUMMARY OF EVIDENCE

The conclusions of all reviews of the evidence are largely favorable toward exercise as a generally beneficial and safe intervention for cancer survivors. However, all include caveats regarding the inconsistencies among results, and the heterogeneity and methodological rigor of trials. Considerable diversity between trials in the study participants, exercise interventions, and outcomes assessed, make comparisons difficult. Furthermore, methodological limitations were common, particularly in the earlier trials. Common weaknesses are listed in Table 2. Encouragingly, methodological rigor has improved in more recent trials, increasing the validity of the reported findings.61,70

The most clearly demonstrated benefit of exercise for cancer survivors is improved physical function, without exacerbation of fatigue or other adverse effects. This strongly implies that patients should attempt to remain active during their treatment, and progressively increase their activity posttreatment to avoid becoming trapped in a perpetuating cycle ofdeteriorating physical conditioning and increasing

Table 2. Common Methodological Limitations in Clinical Trials of Exercise Interventions for Cancer Survivors

Common methodological limitations of trials

Table 2. Common Methodological Limitations in Clinical Trials of Exercise Interventions for Cancer Survivors

Common methodological limitations of trials

Sample

• Small and inadequately powered to detect clinically important changes

• Convenient rather than representative samples

Group allocation

• Randomization not (or inadequately) used

• Inadequate allocation concealment procedures

Assessment

• Primary outcomes not predefined

• Multiple outcomes measured and not corrected for in analysis

• Lack of blinded assessment

Analysis

• Lack of intention-to-treat analysis

• Post-hoc subgroup analysis

fatigue. Preliminary evidence suggests that a range of other positive outcomes are also possible, including lower risk of recurrence, increased survival, and enhanced immune function, quality of life, and psychological well-being.

8.0. EXERCISE PRESCRIPTION GUIDELINES FOR CANCER SURVIVORS

The health-related fitness components of exercise that were discussed earlier, play a key role in the cancer survivor's ability to maintain activities of daily living and other work-related or leisure activities. Therefore, an exercise training program designed to improve each of these components may play a significant role in improving functional capacity in cancer survivors.

As with other clinical populations, cancer survivors should be thoroughly screened prior to commencing any exercise program.97 The screening process should include a medical examination, consisting of a complete medical history, a physical exam, and laboratory tests as necessary.18 A form such as the Canadian Society of Exercise Physiology (CSEP)'s PARmed-X is a useful tool that exercise professionals can supply to medical staff to ensure that an individual's ability to undergo a fitness assessment and begin an exercise program, is assessed appropriately.98 Following medical clearance, assessments to determine the current status of each health-related fitness component should be completed to establish baseline fitness levels. The American College of Sports Medicine (ACSM)18 provides current guidelines for exercise testing and prescription regarding specific fitness assessment techniques. This information will allow an exercise prescription to be tailored according to the individual's strengths and weaknesses in order to maximize the benefits of the training program. Whether the selected fitness assessments of cardiorespiratory and muscular fitness should be maximal or submaximal in nature will depend on a number of factors including the individual's current health status and medical history, the expertise of the assessor, and the equipment available. However, these assessments should test each person to at least the minimum level anticipated for the training program, to ensure they are physically and medically able to begin the program.97 Proposed contraindications regarding exercise testing have been described,99 and should be considered before conducting fitness assessments with cancer survivors.

A complete exercise training prescription should include, at a minimum, the frequency, mode, duration, and intensity of the exercise to be completed.18 Frequency and duration refer to the number of exercise sessions per week, and length of individual sessions respectively. The mode of exercise refers to the type of exercise to be completed and is specific to the relevant fitness component. Intensity is reported in a number of different ways that vary according to the fitness component addressed. Ways of expressing the intensity of aerobic training prescriptions include the percentage of actual (as determined from fitness assessment) or predicted maximal oxygen consumption (VO2max), maximal heart rate (HRmax), or heart rate reserve (HRR), or as a rating of perceived exertion (RPE). The intensity of resistance training prescriptions can be reported as a percentage of one-repetition maximum (1 RM), the amount of weight that can be lifted a specified number of times (e.g., 10 RM = maximum weight that can be lifted 10 times), or RPE.

In addition, three training principles should be applied when designing an exercise prescription: specificity, overload, and progression.18 The principle of specificity suggests that to achieve a certain outcome from an exercise training program, it must be designed to address that particular outcome.18 For example, to improve cardiorespiratory fitness, an aerobic training program would be most appropriate. Alternatively, if the goal is to improve muscular fitness, then a resistance training program should be prescribed. It is also important to note that for resistance and flexibility training, any improvement seen will be specific to the muscles or joints used. It is essential to address this principle and base the exercise program on the needs and goals ofthe cancer survivor to ensure that the desired results are achieved. The second principle, overload, requires that the exercise load must be greater than the body is accustomed to (i.e., greater than required for usual daily activities) for an adaptation (i.e., improvement) to occur.18 For example, a moderate intensity walking program may be sufficient to improve cardiorespiratory in a sedentary individual. However, for a cancer survivor who is already active, this may not exceed usual daily activities, and cardiorespiratory fitness would not improve, unless the exercise stress was increased. The final training principle, progression, is similar to overload but refers to the long-term benefits of exercise training.18 Although applying the overload principle correctly will result in fitness improvements, an exercise training program must gradually increase the volume of training to ensure that improvements continue to occur long-term. The proper application of all three training principles to an exercise prescription will help to maximize the health benefits for the cancer survivor.

Finally, it is important to structure each individual exercise session to include a warm-up, the exercise bout, and a cool-down.18 The warm-up should consist of a general component of light aerobic exercise to gradual increase heart rate and body temperature, followed by a specific component of stretching for all muscle groups to be used during the exercise session. The warm-up may serve to reduce the risk of injury and enhance performance. The exercise bout itself requires the completion of the prescribed volume (time and intensity) and type of exercise. Specific exercise prescription guidelines to improve the health-related fitness components are provided below. The cool-down phase of each workout provides a recovery period from the workout by slowly decreasing the intensity of the activity. Stretching exercises should also be included at the end of the cool-down period. The cool-down allows for the body's systems to return to near-resting values and reduces the chances of cardiovascular events.

While evidence-based exercise guidelines are available for a number of chronic illnesses such as cardiovascular diseases,22 type I and II diabetes,100,101 chronic obstructive pulmonary disease,102 and psychiatric diseases,19 no such guidelines are available for cancer survivors.60 Although no consensus on the appropriate exercise guidelines for cancer survivors has been reached, a number of sources have provided recommendations for prescribing exercise for this population.60 Despite the lack of consensus on the volume and type of exercise that is optimal for cancer patients, it is likely that an exercise program aimed at maintaining or improving the health-related fitness components in cancer survivors would need to minimally meet the recommendations for maintaining or improving these variables in apparently healthy individuals. The Centre for Disease Control in conjunction with ACSM have suggested that individuals complete a minimum of 30 minutes of light to moderate physical activity on most (if not all) days of the week.103 ACSM has since provided more specific guidelines to improve health-related fitness outcomes.20 Table 3

Table 3. Summary of ACSM Guidelines for Maintaining or Improving Cardiorespiratory Fitness, Muscular Fitness, and Flexibility20

Fitness component

Training variable

Suggested prescription

Comments/suggestions

Cardiorespiratory Frequency Intensity

Flexibility

3-5 days/week 55/65-90% of VO2max or HRmax 40/50-85% of HRR 12-16 RPE

Duration 20-60 minutes

Type

Muscular fitness Frequency

Intensity

Duration

Type

Frequency Intensity

Duration Type

Large muscle groups involved, continuous activity 2-3 days/week

MS: 80-90% of 1 RM, ME: 60-70% of 1 RM 16 RPE (Prior to Failure) OR 19-20 RPE (Point of Fatigue) on last repetition 1 set of 3-20 repetitions (MS: 3-8 repetitions; ME: 12-20 repetitions)

8-10 exercises to target major muscle groups

2-3 days/week (Preferably each day) The muscle/joint should be stretched to a point of tension at the end of ROM 15-30 seconds/stretch 2-4

times/stretch Slow and controlled static stretching for all major muscle groups

Exercise duration will depend on intensity chosen (e.g., lower intensity exercise should be longer in duration, and vice versa) Exercise may be completed in smaller exercise bouts of 10 minutes throughout the day Pick an activity that will be enjoyed

At least 24 hours should be allowed between workouts of same muscle group

Ranges between those provided for MS and ME will benefit both aspects of muscular fitness, but not to the same extent as being trained alone

Rest periods between sets should increase with decreasing repetitions (i.e., increasing weight) Progression to multiple sets should be included if time allows Should include core/stabilizing exercises in addition to upper and lower body exercises Can be included in the warm-up and cool-down phases of every workout No pain should be felt throughout the entire ROM

Stretches may be held for up to 1 minute

HRR = heart rate reserve; VO2max = maximal oxygen consumption; HRmax = maximum heart rate; RPE = rating of perceived exertion; MS = muscular strength; ME = Muscular endurance; 1 RM = one-repetition maximum; ROM = range of motion.

provides a summary of these guidelines along with some additional comments and suggestions to aid in their application. Additionally, ACSM has suggested exercise guidelines specific to improving and/or maintaining these health-related fitness components in older adults.104 A comprehensive exercise program should be designed to include cardiorespiratory, resistance, and flexibility training.18 Although the focus of the exercise prescription will vary according to each individual cancer survivor's needs, goals, and personal preferences, it is important that a training program attempts to maintain each fitness component at a minimum. Once exercise training has improved a fitness component to the desired level, it has been suggested that the maintenance of the exercise intensity will maintain that particular fitness component even with corresponding reductions in both frequency and duration.18 Cancer survivors initiating an exercise training program should begin at the lower end of the ranges provided for frequency, intensity, and time, when using the ACSM guidelines. It may be necessary to initiate an exercise program at levels lower than these recommendations depending on the individual's current medical status, treatment stage, and fitness/activity levels. In these cases, the volume of physical activity can be gradually progressed to meet the minimum guidelines. For any individual, progression should be gradual with no more than one variable increased at a time (e.g., intensity or duration, but not both).97 Furthermore, specific contraindications and precautions for exercise have been outlined for cancer survivors who are currently receiving,53 or have completed,105 treatment, which should be considered in addition to those contraindications that are suggested for the general population.18,99

9.0. FUTURE RESEARCH

In 2001, Courneya and Friedenreich published the PEACE (Physical Exercise Across the Cancer Experience) framework, providing a broad structure within which research on physical activity and cancer could be organized and planned.106 The framework breaks down the cancer experience into six phases: two prediagnosis (prescreening and screening) and four postdiagnosis (pretreatment, treatment, posttreatment, and resumption), and identifies eight cancer control outcomes that may be influenced by exercise during the different phases. For some of these outcomes, studies have already been published or are underway. For others there is little previous or current research. The framework helps locate the gaps in the evidence base, thereby providing directions for future investigation (see Figure 1).

During the prescreening time period, the outcome of interest is primary prevention of cancer. There is already a sizable body of data on the role of exercise in cancer protection, and continued research will help to define more clearly the amounts and types of activity required to reduce risk at specific cancer sites, and to understand the mechanisms underlying the protective effects.

In relation to screening, there may be potential for physical activity to compromise the validity of screening tests, hence interfering with cancer detection. Several studies have investigated the effect of cycling on blood concentrations of prostate specific antigen (PSA), which is used in diagnostic testing for prostate cancer. Although some cases of elevated PSA concentrations after cycling have been reported, other studies have found no change, and the issue is unresolved.107 A further possible area of investigation in relation to physical activity and detection is a potential role of exercise in helping to reduce anxiety associated with screening tests and results.

Prevention ^^ Detection

Prescreening t

Screening

PREDIAGNOSIS

Buffering ^^ Coping

Rehabilitation

Palliation

Health promotion

Survival

Palliation

Pretreatment

Treatment

Posttreatment

Resumption

POSTDIAGNOSIS

POSTDIAGNOSIS

DIAGNOSIS

Figure 1. Framework PEACE: An Organizational Model for Examining Physical Exercise Across the Cancer Experience. Reprinted with permission from Courneya KS. and Friedenreich CM106

In the pretreatment phase, a potential buffering role of exercise has been identified where improving fitness prior to commencing therapy, may allow patients to better withstand aggressive treatments. Little research has focused on this question so far.

During treatment, interest in the impact of exercise is focused on coping outcomes. As discussed earlier in this chapter, existing research has provided preliminary data that physical activity has positive effects on various functional and quality of life outcomes in cancer survivors during therapy. Although the bulk of the data relates to women with breast cancer, there are an increasing number of trials investigating other cancer populations. Researchers are also trying to address questions regarding the different dimensions of exercise interventions (e.g., type, frequency, intensity) in order to optimize coping benefits for patients.

During the posttreatment phase, principal outcomes relate either to rehabilitation, with the aim of restoring successfully treated patients as far as possible to normal function and well-being, or to palliation where the purpose is to alleviate the symptoms of those patients who cannot be cured. Relatively few exercise trials have targeted this time period so far, with most concentrating on either patients receiving active treatment or long-term survivors.

The final phase defined in the PEACE framework is resumption, during which the potential value of physical activity is for health promotion purposes, similar to the general population. Several studies have reported that physical activity levels among cancer survivors are lower than they were before diagnosis,108-110 although one large study suggested that the numbers of survivors meeting recommended activity guidelines were similar to individuals without a history of cancer.111 A recent review suggested that cancer diagnosis may represent a teachable moment for promoting positive lifestyle changes such as increased activity, that contribute to improved health and well-being.56 As discussed in the earlier chapter on exercise motivation and behavior change, there are a number of ongoing studies testing interventions targeting exercise behavior change in cancer survivors.

The last cancer control outcome identified that might be related to exercise is survival. The preliminary data discussed earlier in this chapter are encouraging with respect to exercise contributing to increased survival for breast and colorectal cancer,29,31 and further studies of this kind will provide additional information about the value of exercise on this important outcome.

10.0. CONCLUSION

In summary, research activity in the field of physical exercise and cancer is thriving. There is a growing body of evidence indicating a positive effect of physical activity in the primary prevention of cancer. Although only limited data are presently available regarding the potential of exercise to prevent recurrence and increase survival, preliminary findings are encouraging. There are a number of trials to support recommendations that cancer patients should remain physically active during cancer treatment in order to preserve fitness and function, and retain independence in performing activities of daily living. Furthermore, physical activity is an important part of health promotion among cancer survivors for encouraging positive lifestyle changes that contribute to optimizing health and well-being. Finally, ongoing research is attempting to fill current gaps in the evidence base with the aim of enhancing the understanding of the effects of exercise on cancer control outcomes across the entire cancer experience from prevention, through treatment, recovery or palliation, toward long-term survivorship.

ACKNOWLEDGMENTS

Clare Stevinson is supported by a Postdoctoral Fellowship from the Faculty of Physical Education and Recreation, University of Alberta. Kristin L. Campbell was supported by a studentship from the Alberta Heritage Foundation for Medical Research at the time of writing this chapter. Christopher M. Sellar is supported by a studentship from the Alberta Heritage Foundation for Medical Research. Kerry S. Courneya is supported by the Canada Research Chairs Program and a Research Team Grant from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and the Sociobehavioral Cancer Research Network.

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