Physical activity as a standard cancer treatment.

Adequate physical activity is a cornerstone of physical health and mental well-being. Many cancer survivors who have a good prognosis are at higher risk of dying from other causes, such as cardiovascular diseases, and could possibly reap the same benefits of exercise as individuals without a cancer diagnosis. Furthermore, the physical and mental stresses of a cancer diagnosis, including side effects of treatments, present the cancer survivor with additional challenges. An increasing body of literature, including randomized trials, demonstrates the benefits of physical activity on physiological parameters, quality of life, functional status, fatigue, and depression for at least some cancers. Despite acknowledging potential risks of some specific physical activities at certain intensities for some subgroups of cancer survivors, many organizations, such as the American Cancer Society (1), the World Cancer Research Fund and the American Institute for Cancer Research (2), the American College of Sports Medicine (3), and the US Department of Health and Human Services (4), now advocate physical activity for cancer survivors. Details regarding the type, duration, and intensity of exercise will have to be tailored to the individual patient, depending on various factors such as age, physical health, specific cancer, and treatments; however, the vast majority of patients will likely benefit to some degree from physical activity. In this issue of the Journal, Ballard-Barbash et al. (5) extensively review the potential effects of physical activity on cancer-specific and all-cause mortality. They also summarized the effect of physical activity interventions on potential intermediate biomarkers of cancer progression, such as insulin. Unlike previous reviews, which focused on functional health and quality of life, this review addresses the more provocative question of whether physical activity can actually improve cancer-specific survival. Many may accept general health benefits of physical activity for cancer survivors, but the implication of a direct anticancer effect could engender some skepticism. Given the limited success that the most potent and cleverly designed drugs have had on cancer to date, why should something as seemingly simple as walking have potent anticancer activity? We are far from having definitive answers to this question, but as reviewed by Ballard-Barbash et al. (5), perhaps, we are getting closer to an answer. Whereas most cancer therapies to date focus on killing the tumor, physical activity may offer two complementary roles for standard cancer therapy. First, cancer-specific mortality, although generally attributed to the destructive behavior of the tumor, is also dependent on the general health of the patient. Overall health status is inherently integrated and substantially influenced by factors such as physical activity. For example, diabetics who develop cancer have increased overall mortality and, perhaps, cancer-specific mortality compared with nondiabetics with cancer (6), and physical activity is one of the strongest protective factors against diabetes. Even the attribution of cause of death in a cancer patient can be fraught with difficulties ( 7). Second, physical activity could have direct effects on the tumor that are mediated through alterations of various hormones, including insulin, insulinlike growth factor 1, estrogen, and adiponectin. Many of these hormones, and others, have been associated with cancer risk and prognosis, which indirectly supports a causal role of physical activity on cancer-specific death (8). These factors may promote or inhibit tumor cell growth, and thus directly affect tumor progression. Exercise also has immunemodulating effects, which theoretically could affect cancer development or progression. The strongest evidence of a causal association between physical activity and cancer-specific mortality would require a randomized intervention trial. Some ongoing interventions, as described by Ballard-Barbash et al. (5), may provide important data. Currently, the best evidence is from observational studies, and the results thus far appear promising. Breast cancer has received the most study (17 studies), followed by colorectal cancer (six studies), with sporadic studies for some other cancer sites. Most studies suggest that more physically active individuals after diagnosis have better cancer