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Physical activity and cancer outcomes: Growing evidence for the oncologist
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I have been running regularly throughout most of my adult life, beginning at school, through medical school and to the present day.
My runs have reduced in intensity, length and frequency over the years, but I still find running to be relaxing and a great way to get outside. I also find my time pounding the pavement to be good thinking time.
When I analyze why I still try to keep a regular exercise regimen after 40-plus years, I can think of several reasons — I enjoy it, it helps control my weight, I can probably eat more as a result (!) and it has other potential health benefits, including blood pressure control, lipid levels and so on. It is not always equally enjoyable — when it is dark and cold, I tend to retreat to the warmth and comfort of the elliptical in my basement — but my moderate level of exercise has become part of my lifestyle. So, in reality, I do not analyze it very much; it is just something I do.
Clear association, unclear mechanism
I recently took part in an educational and informational event for patients with chronic lymphocytic leukemia. The Q&A session was lively, as they usually are, with many of the questions directed at lifestyle, nutrition and exercise and their role in the behavior of CLL. This is certainly not limited to the CLL community — questions about diet and exercise are among the most common I am asked in clinic. I suspect the same is true of many of those reading this column.
In contrast, the other subject that took up a considerable chunk of time involved the role of chimeric antigen receptor (CAR) T cells in CLL. It is surprising — and a little disappointing — that I am able to cite more evidence for a complex, high-cost and highly intensive intervention like CAR T cells than I can for a low-intensity, low-cost and simple intervention like an exercise program or diet.
The role of physical activity and cancer outcomes has been investigated in studies of variable quality over many years. Studies correlating higher levels of physical activity with improved cancer survival have been reported repeatedly, but have been confounded by whether there is a true causal link or whether this is simply a reflection of performance status. Do physically active people have better cancer outcomes because of increased activity, or are these observations simply the result of those with higher performance status having better outcomes? That is not exactly a new observation.
Data suggest that interventions aimed at increasing physical activity in the postdiagnosis setting may improve cancer survival, possibly in a disease-specific fashion.
But, the mechanisms for this are still somewhat obscure.
Given the well-documented association between obesity and cancer survival and the inverse relationship between exercise and obesity, it is not surprising that many hypotheses suggest that the biologic effect of exercise is related to reversing the oxidative stress, insulin resistance and impaired immunity associated with obesity. Additionally, direct mechanisms for the effect of exercise on cancer survival include elevation of insulin-like growth factor binding proteins, which can inhibit tumor growth.
But, mechanistic hypotheses are relatively few, and current thinking on this subject has been largely guided by observational studies. A systematic review of many of these studies has shown a positive correlation between postdiagnosis physical activity and survival for diseases such as breast, colon and prostate cancer, some of which have controlled for prediagnosis physical activity, which can be a confounding factor.
Overall, a growing body of observational evidence supports a possible role for physical activity in cancer survival, but the magnitude of the effect is unclear. We do not have the benefit of completed randomized trials to inform our discussions with patients regarding this issue.
Although very limited at the moment, some randomized trial data are now becoming available.
The randomized START study compared usual care with supervised aerobic or resistance exercise in patients with breast cancer and documented an improvement in 8-year DFS for the combined exercise group compared with the usual care group (82.7% vs. 75.6%).
The CHALLENGE trial, a large randomized study of exercise in patients with colorectal cancer, is in progress to compare a structured physical activity program with usual care in patients with high-risk stage II and stage III disease who have completed chemotherapy. This study is actively accruing but, in an early report, has been able to demonstrate that the use of a structured exercise program can change behavior — reported exercise levels in the intervention group were significantly higher than in the control group.
A randomized trial of posttherapy physical activity in men with prostate cancer also is underway.
Recommendations for our patients
Evidence from these studies is likely to take several years to emerge, so what do we do in the meantime?
One priority area for investigation should be to look at strategies likely to increase physical activity in cancer survivors. As I mentioned, I now regard my fairly moderate exercise program as part of my routine lifestyle, but that is the result of many years of being “conditioned” to this state. How would we provide meaningful advice and motivation to a person with cancer — just emerging from surgery, chemotherapy or radiation, whose lifestyle may be sedentary — that an exercise program may help them?
There already is a large body of data from controlled studies to suggest that a moderate exercise program improves strength, fitness, quality of life, sleep, fatigue and depression among cancer survivors. These data alone do not seem to have convinced many cancer care providers to actively refer their patients to exercise programs, or for cancer centers to develop structured physical activity regimens. Fortunately, the number of cancer centers that do offer such programs — including our own — is growing.
As data continue to emerge on the impact of physical activity on cancer outcomes, evidence suggests that patients will look to us as oncologists to guide their decisions about physical activity.
In a thoughtful article published in Journal of Clinical Oncology, Hardcastle and Cohen point out that most patients with cancer want to receive information about physical activity from their oncologists, and they are more likely to engage in a program if their oncologist recommends it. The authors also summarize various strategies for motivating patients and helping with health and wellness behavior changes.
Like many other physicians, I now tell my patients evidence is growing — but not fully established — to support that a physical activity program may improve cancer outcomes. I encourage them to be active and to enroll in one of our own in-house programs, if possible. Evidence suggests that this approach is more likely to be successful than enrollment in a regular gym or an unstructured program of exercise. That said, what constitutes moderate exercise is variable, and the widely used definition is more than I manage in a typical week!
If randomized data show a positive impact of physical activity on outcome, we will need to make sure that we have resources available to provide the necessary coaching and encouragement, as well as robust strategies for engaging patients in such programs from a general wellness and cancer survival perspective.
This might prove to be a low-cost, high-impact intervention and, who knows — it might provide added benefit for those patients who receive CAR T cells.
References:
Courneya KS, et al. Cancer Epidemiol Biomarker Prev. 2016;doi:10.1158/1055-9965.EPI-15-1267.
Courneya KS, et al. Med Sci Sports Exer. 2014;doi:10.1249/MSS.0000000000000297.
Friedenreich CM, et al. Clin Cancer Res. 2016;doi:10.1158/1078-0432.CCR-16-0067.
Hardcastle SJ and Cohen PA. J Clin Oncol. 2017; doi:10.1200/JCO.2017.74.6032.
Jayasekara H, et al. Int J Cancer. 2017;doi:10.1002/ijc.31049.
For more information:
John Sweetenham, MD, FRCP, FACP, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director of Huntsman Cancer Institute at University of Utah. He can be reached at john.sweetenham@hci.utah.edu.
Disclosure: Sweetenham reports no relevant financial disclosures.