Despite the clearly established overall health benefits of exercise, its role in reducing prostate cancer risk is unclear. Whereas some studies found often dramatic reductions in prostate cancer risk, others found no effect.
Despite the clearly established overall health benefits of exercise, its role in reducing prostate cancer risk is unclear. Whereas some studies found often dramatic reductions in prostate cancer risk,[1-3] others found no effect.[4-6] Naturally, for men who do develop prostate cancer, the question is no longer whether exercise can prevent prostate cancer but rather whether it can prevent prostate cancer progression. Unfortunately, we have little evidence on which to make recommendations. Given the limited availability of data in this setting, a recent review of the literature evaluated observational studies and clinical trials addressing the impact of physical activity and exercise on patients at different stages of prostate cancer.
In this issue of ONCOLOGY, Dr. Ramalingam and colleagues provide a concise overview of evidence that physical activity and exercise benefit men with prostate cancer. Specifically, the authors first discuss the Prostate Cancer Lifestyle Trial, which randomized patients with low-grade prostate cancer to an intensive lifestyle program that included a vegan diet supplemented with soy, fish oil, vitamin E, selenium, and vitamin C; stress management; moderate aerobic exercise; and a 1-hour support group weekly vs a placebo arm with no intervention. At 1-year follow-up, those who had adhered to the total lifestyle intervention had decreased levels of prostate-specific antigen and a lower likelihood of undergoing treatment. Differences in treatment rates were maintained up to 2 years. While studies with longer follow-up are warranted, the Prostate Cancer Lifestyle Trial shows the promise of lifestyle changes in affecting prostate cancer progression. However, it should be noted this was not an exercise study, but rather a global lifestyle trial. Of key importance is that men in the intervention group lost 10 pounds, on average. Given that weight loss slows prostate cancer growth in animal models and likely has the same effect in humans, it is conceivable that the entire benefits of the intervention were due to weight loss and not to exercise. While exercise clearly has metabolic benefits, exercise alone is usually ineffective for achieving weight loss.
Dr. Ramalingam and coauthors further summarized the data from three large observational studies that found inverse associations between physical activity and prostate cancer progression, as well as overall and prostate cancer–specific mortality, among men with localized disease. First, a substudy of 1,455 men with localized prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database showed that men who walked briskly for 3 hours weekly or more had a 57% lower rate of progression, defined as biochemical recurrences, secondary treatments, bone metastases, and prostate cancer deaths, than men who walked at an easy pace for less than 3 hours per week. Furthermore, among 2,705 men with nonmetastatic prostate cancer from the Health Professionals Follow-Up Study, those with at least 3 hours per week of vigorous activity had a 61% reduced risk of prostate cancer–specific mortality compared with less active men. Of note, this benefit was not observed for men with lower physical activity levels. As Dr. Ramalingam and coauthors mention, further suggestion that exercise may have prostate cancer benefits comes from the National Prostate Cancer Register of Sweden, a large study of 4,623 men in which improved prostate cancer–specific survival was seen with as little exercise as walking/bicycling at least 20 minutes daily or exercising at least 1 hour per week. On the whole, these studies suggested that some physical activity is better than none when assessing non–prostate cancer-related outcomes. However, at least some studies suggest that to gain prostate cancer–specific benefits, higher intensity and more prolonged activity may be required. Although these results look promising, these are observational studies with self-reported assessments of physical activity, which generate major concerns about confounding factors (eg, men who exercise may be more health-conscious and therefore seek care earlier and have better nutrition), as well as reverse causation (eg, patients with advanced cancer were too sick to exercise); randomized controlled studies are needed to prove these benefits. Moreover, the effect of physical activity in men with advanced cancers remains to be studied.
In their review, Dr. Ramalingam et al further explored the effect of physical activity on men receiving radiation and androgen deprivation therapy (ADT). While aerobic exercise improved short-term fatigue and fitness in men undergoing radiation therapy, resistance exercise improved long-term fatigue, quality of life, and muscle strength. For men on ADT, resistance exercise improved muscle strength, fitness, and quality of life; and unlike aerobic exercise, it mitigated the loss of lean body mass caused by androgen deprivation.[16,17] Given these benefits, we believe exercise should be considered the standard of care for men with prostate cancer undergoing radiation and ADT. For these men, appropriately prescribed exercise regimens, including both aerobic and resistance exercises, may ameliorate a range of treatment-induced side effects. Further study is required, however, to determine whether exercise improves cancer control.
While Dr. Ramalingam and colleagues provided abundant evidence supporting the health benefits of physical activity in general, this relationship is well-known. Whether physical activity specifically slows prostate cancer growth remains to be determined. Moreover, should physical activity indeed slow prostate cancer progression, the authors did not discuss the mechanisms by which this may occur. Although precise biological pathways remain to be fully elucidated, the potential beneficial effects of physical activity may be mediated by a variety of mechanisms-including modulation of circulating factors such as insulin and growth factors, decrease in adipose tissue, reduction of inflammation and oxidative stress, modulation of tumor blood flow, and improvement of immune function. In vitro studies from the Prostate Cancer Lifestyle Trial showed that the growth of LNCaP (lymph node carcinoma of the prostate) cells was inhibited almost eightfold by serum from patients in the intervention group compared with serum from the control patients. This effect has been attributed to the increased serum levels of tumor suppressor proteins, such as insulin-like growth factor binding proteins 1 and 3, and decreased serum levels of tumor-promoting proteins, such as epidermal growth factor and insulin-like growth factor 1, leading to activation of cellular p53, p21, and caspases, which collectively results in slowed tumor growth. In addition, physical activity may affect prostate cancer growth by reducing inflammation. Physical activity lowers levels of inflammatory factors such as C-reactive protein and interleukin-6; increases levels of anti-inflammatory cytokines; and inhibits production of pro-inflammatory cytokines, which have been shown to promote cell proliferation and inhibit apoptosis of prostate cancer cells in vitro.
Despite this oversight, we do applaud the authors for providing practical methods by which clinicians can assess and implement physical activity regimens for their patients with prostate cancer. Given the overall health benefits of physical activity, there is no doubt that patients should be exercising, although as previously mentioned, it is unclear at this time whether this intervention truly has an impact on prostate cancer progression. Dr. Ramalingam and coauthors recommend the 5 A’s (ask, advise, assess, assist, and arrange) strategy based on its use in smoking cessation programs. Just as successful smoking cessation begins with identifying smokers and appropriate interventions based upon the patient’s willingness to quit, the 5 A’s may be a framework for engaging prostate cancer patients in conversations about their levels of physical activity.
In summary, the authors highlight data from observational studies and clinical trials addressing the impact of physical activity and exercise on men with prostate cancer. While larger randomized controlled trials are required to confirm and expand current findings, the authors present convincing evidence that men with localized disease should stay physically active to improve their overall health and mitigate the side effects of radiation treatment and ADT. Whether these behavior changes will improve their cancer prognosis is unclear. However, even if physical activity has no effect on the cancer, given the well-known benefits for cardiovascular and overall health, all men living with prostate cancer should be advised to be physically active.
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.
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