ABSTRACT: An informal review of literature on exercise and cancer was undertaken in order to examine the role of exercise in cancer prevention, treatment, rehabilitation, and late survivorship. Population-wide studies show that cancer incidence decreases with increasing physical activity levels. Exercise can decrease the side effects of anticancer therapy, and can aid in recovery and rehabilitation following chemotherapy, radiation, and surgery. Observational studies of breast, colon, and prostate cancer survivors show robust associations between postdiagnosis exercise and decreased cancer-specific mortality. In addition, all-cause mortality in cancer survivors decreases with increasing amounts of exercise. The amount and intensity of exercise required to measure a survival benefit appear to vary by primary tumor type. Decreased breast cancer mortality is seen with the equivalent of 3 hours of walking per week, and decreased colon cancer mortality with 6 hours of walking per week. For these tumors, more vigorous exercise may not improve survival. However, after a prostate cancer diagnosis, more intense exercise is associated with superior survival when compared with walking. The mechanisms behind these differences remain to be elucidated. Further research is also needed to determine the various amounts and intensities of exercise required for optimum cancer prevention, recovery, and survival.

Introduction

“Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise save it and preserve it” — Plato (427–347 BC)

Physical activity intersects with oncology in both the pre-diagnosis and survivorship settings. That physical activity plays a role in the prevention of many cancers is well known, as is the role of exercise in decreasing treatment side effects, speeding recovery after a cancer diagnosis, and enhancing survival. This article will review these intersections of exercise and oncology, discuss the known mechanisms by which exercise exerts its salutary effects, and touch upon the future directions of exercise research in the oncology setting. Finally, recommendations are provided for clinicians to help patients with and without cancer take advantage of the benefits of physical activity.

Regular Exercise Is Associated With Decreased Cancer Risk

That exercise decreases cancer risk is well known, as many studies document the population-wide inverse association between physical activity and cancer incidence. Epidemiologic data from 73 studies conducted around the world, for example, indicate a 25% reduction in the risk of breast cancer among the most physically active women compared with those who are least active.[1] A recent meta-analysis of 19 studies documents the inverse association between kidney cancer and physical activity.[2] Similarly, numerous studies have established the protective role exercise plays in decreasing the risk of many other cancers, including lung, endometrial, colon, and possibly prostate cancer.[3-6]

Regular Exercise May Not Protect Against Health Risks Associated With Prolonged Daily Sitting

However, the dangers of inactivity are especially problematic among those who are consistently sedentary. The possibility that spending more than 4 hours a day behind a desk or working at a computer increases the risk of many chronic diseases, including cancer, has recently gained attention.[7,8]

The extent of the association between sitting and cancer is not fully known. However, current studies, suggesting that regular exercise may not ameliorate the deleterious effects of prolonged sitting,[9] raise concern. That is, an office worker who exercises daily may still incur an increased risk of cancer simply by sitting for more than 4 hours every day.

A timer can be used to remind persons whose job requires prolonged sitting to rise at least once an hour. Suggested activities include climbing a flight or two of stairs, stretching, calisthenics, or taking a short walk. Some office workers make a habit of taking all phone calls standing up. In addition, if the workplace permits, treadmill desks are available from various manufacturers, or a simple one can be constructed in a home shop. Treadmill desks allow reading, writing, or working on a computer while walking very slowly, typically at the rate of 1 mile per hour.

Physical Activity During Cancer Therapy Decreases Treatment Side Effects

In the middle years of the last century, exercise was not recognized as an important part of cancer treatment. The prevailing notion at the time was that cancer patients undergoing cytotoxic treatments should avoid exertion. However, a 1989 randomized trial of 45 women undergoing adjuvant chemotherapy for stage II breast cancer demonstrated that 10 weeks of interval-based, aerobic exercise not only improved functional capacity and body composition, but it also decreased chemotherapy-induced nausea. This pioneering work demonstrated that aerobic exercise was feasible, safe, and beneficial for patients undergoing chemotherapy. [10-12]

Studies since then have carefully documented the positive effects of exercise on patients undergoing chemotherapy or radiation therapy for many different types of cancer.[13-15] At least one study shows that this decrease in symptom burden extends to elderly patients who exercise while in treatment, including improved self-reported health during and after treatment, less memory loss and shortness of breath during treatment, and less fatigue following completion of treatment.[16]

Exercise has also been shown to ameliorate the sexual dysfunction of men undergoing androgen deprivation therapy for advanced prostate cancer.[17] Fifty-seven men on androgen suppression therapy for prostate cancer were randomized to an exercise group or a sedentary control group. The exercise intervention consisted of supervised aerobic activity and resistance training. After 12 weeks of exercising twice weekly, men in the intervention group reported increased sexual interest and activity. In contrast, sexual interest and activity decreased over the same period among men in the control group.

High-Intensity Activity Provides More Benefits Than Light Activity

A recent Cochrane database systematic review of 56 trials encompassing 4,800 subjects found that compared with light exercise, moderate-intensity or vigorous exertion during cancer treatment provided greater improvements in health-related quality of life, physical functioning, anxiety, fatigue, and sleep disturbances.[18]

This suggests that for patients on chemotherapy or radiation, and without contraindications to vigorous exercise, even more benefits will accrue with high-intensity activity. In this Cochrane review, mild exercise was defined as a level of activity that raised the heart rate to 30% to 54% of maximum. Examples of low-intensity activities include walking at a rate of 2 to 3 miles per hour or bicycling at 10 miles per hour. Moderate exercise was defined as activity carried out at 55% to 70% of maximum heart rate. Walking at 3 miles per hour or bicycling at 10 to 20 miles per hour are examples of moderate-intensity activity. Finally, vigorous exercise was defined as that requiring 71% to 95% of maximum heart rate. Running at 5 miles per hour or faster, or bicycling at a speed greater than 20 miles per hour would be considered vigorous activity.

Exercise in the Early Survivorship Stage

Exercise plays a major role in the recovery of function following treatment, and in reducing the lingering effects of both the disease and its treatment. A Canadian systematic review and meta-analysis of 14 randomized controlled trials reporting the effects of exercise on 717 breast cancer survivors 35 to 72 years of age showed that exercise consistently increased cardiorespiratory fitness and quality of life, and, less consistently, decreased fatigue.[19]

As in the treatment phase, the optimal type and frequency of exercise that will most enhance recovery in the early-survivorship stage of cancer is unknown. What is becoming clear, however, is that low-intensity exercise typically provides little relief from insulin resistance, adiposity, and excessive inflammation, all of which are considered pertinent to the progression of many common cancers.

In the RESTORE trial, 82 women enrolled within 4 to 12 weeks of surgery for early-stage breast cancer were randomized to exercise plus lymphedema education or to lymphedema education only. The exercise program consisted of 30 minutes of moderate walking, 20 minutes of upper and lower body strength training, and 10 minutes of stretching, all done twice a week for 18 months. Adherence through the 18-month period was 79%. Although a significant improvement in the
6-Minute Walk Test was reported in the exercise group, no benefit was seen in other parameters, such as quality of life.[20]

This study and other studies demonstrate that not all exercise is equally beneficial for cancer survivors, and that physicians still have little to guide them when deciding how to prescribe exercise for a particular patient.

The authors of the Canadian meta-analysis described above note “the wide variability in study interventions,” and conclude that “the diversity in exercise prescription is not surprising, given the lack of consensus on the optimal exercise prescription for this patient population.”[19] In the 14 studies comprising the Canadian review, the exercise modalities ranged from walking to weight lifting, stationary cycling, tai chi, and jogging, highlighting the need for more orderly assessment of exercise modalities in future research.

In addition, optimal timing of exercise in relation to the cancer-survivorship spectrum may be important. For example, in the same Canadian meta-analysis of exercise studies in breast cancer survivors, the two studies demonstrating an improvement in fatigue were conducted in the post-treatment period. The six studies done in the adjuvant setting found no reduction in fatigue with exercise.

To address these issues, studies are underway to determine the effects of various exercise schedules and modalities on metabolism and fitness.[21]

Finally, patients in the early-survivorship stage often have specific rehabilitation needs related to surgery, radiation, chemotherapy, or the cancer itself. Lymph node dissection and/or axillary radiation can lead to lymphedema of the arm in breast cancer survivors, and this may interfere with exercise enjoyment. Life-saving chemotherapy drugs can leave survivors with peripheral neuropathy. The resulting pain and numbness can affect both the ability and the desire to exercise in previously enjoyable ways. Patients who require limb-sparing surgery for sarcoma treatment may require occupational and physical therapy. Referral to a rehabilitation specialist is appropriate for these patients.