Review Controlled Physical Activity Trials in Cancer Survivors: A Systematic Review and Meta-analysis Kathryn H. Schmitz, 1 Jeremy Holtzman, 3,4 Kerry S. Courneya, 5 Louise C. Ma ˆsse, 6 Sue Duval, 2 and Robert Kane 3,4 1 Division of Clinical Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Divisions of 2 Epidemiology and 3 Health Services Research and Policy; 4 Clinical Outcomes Research Center, University of Minnesota, Minneapolis, Minnesota; 5 Faculty of Physical Education, University of Alberta, Edmonton, Alberta, Canada; and 6 Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland Abstract Background: Approximately 9.8 million cancer survivors are alive in the United States today. Enthusiasm for prescribing physical activity for cancer survivors depends on evidence regarding whether physical activity during or after comple- tion of treatment results in improved outcomes such as cardiorespiratory fitness, fatigue, symptoms, quality of life, mental health, or change in body size. Methods: A systematic qualitative and quantitative review of the English language scientific literature identified con- trolled trials of physical activity interventions in cancer survivors during and after treatment. Data from 32 studies were abstracted, weighted mean effect sizes (WMES) were calculated from the 22 high-quality studies, and a systematic level of evidence criteria was applied to evaluate 25 outcomes. Results: There was qualitative and quantitative evidence of a small to moderate effect of physical activity interventions on cardiorespiratory fitness (WMES = 0.51 and 0.65 during and after treatment respectively, P < 0.01), physiologic outcomes and symptoms during treatment (WMES = 0.28, P < 0.01 and 0.39, P < 0.01, respectively), and vigor posttreatment (WMES = 0.83, P = 0.04). Physical activity was well tolerated in cancer survivors during and after treatment, but the available literature does not allow conclusions to be drawn regarding adverse events from participation. Conclusions: Physical activity improves cardiorespiratory fitness during and after cancer treatment, symptoms and physiologic effects during treatment, and vigor posttreatment. Additional physical activity intervention studies are needed to more firmly establish the range and magnitude of positive effects of physical activity among cancer survivors. (Cancer Epidemiol Biomarkers Prev 2005;14(7):1588 – 95) Introduction Approximately 9.8 million cancer survivors are alive in the United States today (1), and the population of long-term cancer survivors continues to grow. Current cancer treatments, although increasingly efficacious for improving survival, are toxic in numerous ways and produce negative short and long- term physiologic and or psychologic effects, including pain, decreased cardiorespiratory capacity, cancer related fatigue, reduced quality of life, and suppressed immune function (2). Physical activity has been proposed as a nonpharmacologic intervention to combat the physiologic and psychologic effects of treatment in cancer patients (3). Moreover, cancer and its treatment may increase the risk of other common chronic diseases, such as diabetes or cardiovascular disease. Among survivors who have completed treatment and are otherwise healthy, the American Cancer Society prescribes physical activity levels similar to those prescribed for the general population, for the purpose of general health promotion (4). These same recently published American Cancer Society guidelines suggest that there may not be sufficient evidence of the safety of regular activity among survivors currently undergoing treatment to warrant the potential risk of participating (4). Clinicians who wish to prescribe physical activity for patients currently undergoing cancer therapies need to know whether a physical activity program will reduce the physiologic and psychologic negative effects of treatment. The potential benefits and harms from a physical activity program during active cancer therapy must be balanced against the potential harm from remaining inactive, which also has short-term and long- term health risks. A period of inactivity during (and after) cancer treatment may lead to decreased cardiorespiratory fitness (which could affect the ability to do activities of daily living), bone loss and muscle atrophy, as well as worsening of glucose metabolism, insulin sensitivity, digestive function, immune function, and cardiovascular risk factors (5). Given the growing population of survivors, there is a need to establish the extent to which physical activity is appropriate for cancer survivors during and after treatment, as well as whether physical activity is effective for improving the health and well-being of survivors across the cancer control continuum. The outcomes of interest from a physical activity program for cancer survivors vary according to timing with regard to treatment as well as whether treatment was successful in eradicating the cancer. In addition, clinical advice needs to be based on studies conducted on patients who are at a similar point of the cancer experience (pretreatment, during treat- ment, and posttreatment). For example, a study that reports that physical activity is useful to combat fatigue among survivors who have completed treatment will not assist a clinician in deciding whether to prescribe physical activity for Cancer Epidemiology, Biomarkers & Prevention 1588 Cancer Epidemiol Biomarkers Prev 2005;14(7). July 2005 Received 9/22/04; revised 3/4/05; accepted 4/15/05. Grant support: Agency for Healthcare Research and Quality contract 290-02-009, Task Order 3, to the University of Minnesota Evidence Based Practice Center, under the direction of Robert Kane. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Kathryn H. Schmitz, Division of Clinical Epidemiology, University of Pennsylvania, 423 Guardian Drive, 9th Floor Blockley Drive, Philadelphia, PA 19072. Phone: 612-625-8056; Fax: 215-898-0901. E-mail: kschmitz@cceb.upenn.edu Copyright D 2005 American Association for Cancer Research.