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The Role of Physical Activity in Cancer Prevention, Treatment, Recovery, and Survivorship: Page 2 of 2

The Role of Physical Activity in Cancer Prevention, Treatment, Recovery, and Survivorship: Page 2 of 2

Physical Activity in Advanced Cancer

Physical activity also has a role in the setting of advanced cancer, where impaired physical function due to disease progression and anticancer treatment is nearly ubiquitous. A University of Pittsburgh systematic review examined 16 studies involving more than 500 subjects with advanced malignancy, and reported that aerobic exercise, rehabilitation regimens, or group exercise improved physical fitness and function, and increased feelings of vitality.[22] As with other patients who require specialized rehabilitation, it is advisable to refer these patients to an exercise specialist experienced in the care of cancer patients.

TABLE 1

Impact of Physical Activity on Common Cancers

Among the most interesting advances in the field of exercise and cancer in the last decade are several observational studies showing that colon, breast, and prostate cancer survivors who exercise enjoy reduced cancer-specific mortality, and that patients with different cancer diagnoses may require various amounts and intensities of exercise to obtain maximum benefit (see Table 1). The Cancer and Leukemia Group B (CALGB) 89803 cohort consisted of 832 subjects with stage III colon cancer. These patients were followed prospectively for a median of 9.6 years. Compared with subjects exercising an hour or less per week, those walking at least 6 hours weekly displayed a 49% decreased risk of mortality over the course of the study.[23] The Nurses’ Health Study (NHS) reinforced this finding. Among 573 colon cancer survivors, those who exercised at least 6 hours weekly gained a statistically significant cancer-specific survival advantage over those exercising less than an hour a week.[24]Compare those rather high exercise volumes to the lower volumes needed to produce a similar effect in breast cancer patients: A NHS cohort of 2,987 breast cancer survivors required only 3 hours of moderate exercise weekly to achieve a statistically significant decrease in breast cancer–specific survival.[25]

The NHS breast cancer findings were corroborated by the Women’s Health Initiative (WHI) Study. Of the 4,643 postmenopausal women with breast cancer who were enrolled in the study, those who walked briskly for only 3 hours a week had a significantly lower risk of overall mortality compared with inactive women.[26]

Contrast these low exercise volumes and intensities with those in a study of 2,705 men diagnosed with nonmetastatic prostate cancer. This study demonstrated that men who walked briskly for 90 minutes or more each week had a decreased risk of all-cause mortality. Disappointingly, however, brisk walking failed to decrease the risk of prostate cancer–specific death. Furthermore, this study found that more intense exercise carried out for 3 or more hours weekly not only decreased overall mortality compared with just brisk walking, but vigorous exercise also decreased the risk of prostate cancer–related deaths by 61%. Besides walking, other moderate-intensity exercise modalities in this study included golf and weight lifting. Among the more vigorous exercise modalities in this study were squash, running, swimming, tennis, and bicycling.[27]

These studies illustrate the intriguing fact that achieving cancer-specific survival improvements may require less exercise for breast cancer patients than for those with colon cancer, and moreover, that exercise of higher intensity and longer duration may be required to decrease prostate cancer–specific mortality.

In a 2011 review article, Davies et al postulate that exercise-related reductions in breast cancer mortality may be mediated by beneficial reductions in insulin levels, that the benefits of exercise after a diagnosis of colorectal cancer may be related to modulation of oxidative damage to DNA, and that exercise along with a low-fat, high-fiber diet may slow progression of disease in early-stage prostate cancer through a decrease in apoptosis and reductions in levels of serum IGF-1.[28] However, the precise mechanisms through which exercise may influence cancer recurrence and mortality have yet to be established.

Thus, the current guidelines calling for 150 minutes of moderate-intensity aerobic exercise weekly, plus two sessions of resistance training (weight lifting), may not provide equal benefit for all cancer patients.

Current Exercise Guidelines Fail to Decrease Weight or Insulin Resistance

Walking the recommended 150 minutes per week[29] fails to improve adiposity, insulin resistance, and inflammation.[30-36] In addition, walking programs fail to retain adherents; counter-intuitively, the cardiology literature shows that short, high-intensity regimens lead patients to continue exercise regimens for at least 2 years.[37]

Supervised exercise programs incorporating small volumes of high-intensity activity, such as repeated short sprints, not only decrease adiposity and improve insulin sensitivity and inflammation but also achieve these results with an hour or less of exercise per week.[38-41] This may explain why subjects find high-intensity workouts more engaging than walking programs.[42,43]

Specific Populations May Benefit More Than Others

In the NHS breast cancer cohort mentioned above, subjects who enjoyed the greatest decrease in cancer-specific mortality when they began exercising only after diagnosis were overweight or obese, and they had estrogen receptor–positive tumors.[25] This finding suggests a mechanism—amelioration of adiposity, insulin resistance, and inflammation—related to energy-sensing signaling pathways, and it also suggests that exercise interventions can and should be targeted to patients with tumors sensitive to manipulations of energy balance.

Some Tumors May Be Insensitive to Exercise Interventions

Animal studies show that an intact mammalian target of rapamycin (mTOR)/Akt system is required for exercise to produce significant changes in gene expression.[45,46]

Conversely, activating mutations of PI3K and/or loss of PTEN signaling can render tumors resistant to the decreases in insulin and insulin-like growth factor, mediated by caloric restriction and negative energy balance. It is conceivable that such mutations may also render some tumors resistant to exercise-induced decreases in insulin and IGF. [46]

That different modes and combinations of exercise, as well as different schedules, durations, frequencies, and intensities have complex metabolic effects is becoming more widely recognized.[47] In the future, as research enables better understanding of the genetic and epigenetic properties of each tumor and patient, more precisely targeted exercise prescriptions will become possible.

Summary

Exercise assists in cancer prevention, recovery, and survival (see Table 1). In each of these oncologic settings, patients should be counseled to exercise as vigorously as is safe, and to avoid prolonged sitting. The latter should be emphasized as much as the former, as evidence shows that the harmful effects of prolonged sitting may not be ameliorated by regular exercise.

During cancer treatment, exercise should be employed to counter the effects of chemotherapy and radiation, including fatigue and nausea. The current exercise guidelines should be followed, and patients who are able should add some high-intensity exercise to their base of moderate-intensity activity.

In the early survivorship setting, exercise should be employed to speed recovery from the effects of surgery and radiation, to return the patient as much as is possible to full function, and to improve the quality of life. Exercise should be continued in late survivorship, to improve overall and cancer-specific survival. Since overall mortality is decreased by exercise, all cancer survivors should aim for a vigorous physical activity program, one that is tailored to their limitations and meets or exceeds the intensities stipulated by current guidelines.

Current exercise guidelines for cancer patients recommend a base of prolonged aerobic exercise of low-to-moderate intensity, such as walking, carried out at least 150 minutes per week, in divided sessions. Also recommended is a small amount of resistance training. These guidelines are useful for many patients and should be liberally employed at present. However, the lack of major metabolic benefit for many persons adhering to this moderate-intensity regimen is of concern.

For these reasons, exercise regimens that employ high-intensity aerobic
activity are now being assessed in the oncology setting.[48,49]

Genetic and epigenetic variations dictate whether a tumor will respond to perturbations in energy balance such as those induced by exercise. Advances in genomics and metabolomics will eventually allow oncologists to predict not only which patients will benefit from exercise, but also what frequencies, durations, intensities, and modalities of exercise will best exploit a particular tumor’s metabolic vulnerabilities.

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

Editor’s Note: Dr. Lemanne is no longer affiliated with Memorial Sloan-Kettering Cancer Center.

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References

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