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Exercise Interventions for Prostate Cancer Survivors Receiving Hormone Therapy

Systematic Review

Moe, Esther L.; Chadd, Joanna; McDonagh, Marian; Valtonen, Maarit; Horner-Johnson, Willi; Eden, Karen B.; Guise, Jeanne-Marie; Nail, Lillian; Winters-Stone, Kerri M.

Translational Journal of the American College of Sports Medicine: January 1, 2017 - Volume 2 - Issue 1 - p 1–9
doi: 10.1249/TJX.0000000000000025
Review Article
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ABSTRACT Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) often experience adverse effects that negatively affect physical function and quality of life. Exercise may ameliorate those treatment adverse effects, and effective, scalable interventions to increase exercise behaviors are needed. The objective of our review is to evaluate both the efficacy and the implementation methods of exercise interventions for PCS receiving ADT. We searched MEDLINE®, PsycINFO, and the Cochrane Central Register of Controlled Trials through May 2016. Randomized controlled trials of exercise intervention PCS receiving ADT were included. The protocol was registered with PROSPERO (#CRD42015017348). Two authors independently reviewed articles for inclusion and risk of bias. Nine articles describing eight randomized controlled trials were included. The included interventions varied in training type (resistance or aerobic), length of intervention, dose of training (number of exercise sessions per week), and whether training was supervised or unsupervised. Despite heterogeneous interventions, varied measures, and generally short duration of training (average of 12 wk), improvements in fitness, symptoms, physical function, and quality of life were reported. The exercise training sessions were well attended, because few participants discontinued their participation in the exercise interventions, and attendance at supervised exercise sessions ranged from 74% to 94%. Self-reported compliance with the unsupervised exercise component was lower than that with the supervised sessions for trials that reported these data. In conclusion, supervised programs may be less scalable or accessible to populations with limited access. Future efforts should focus on delivery of programs that can adequately scale and contain the features of successful supervised interventions so that broad uptake by PCS on ADT can be achieved.

1Health Promotion and Sports Medicine, Department of Medicine, Oregon Health and Science University, Portland, OR; 2Pacific Northwest Evidence-Based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR; 3KIHU-Research Institute for Olympic Sports, Jyvaskyla, FINLAND; 4Institute on Development and Disability, Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR; 5Obstetrics and Gynecology, Medical Informatics and Clinical Epidemiology, and Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR; 6Knight Cancer Institute, Oregon Health and Science University, Portland, OR; and 7School of Nursing, Oregon Health and Science University, Portland, OR

Address for correspondence: Esther L. Moe, Ph.D., M.P.H., Oregon Health and Science University, CR110, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098 (E-mail: moe@ohsu.edu).

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INTRODUCTION

An estimated 2.8 million men who have been diagnosed with prostate cancer are alive in the United States (45). Prostate cancer is the most commonly diagnosed cancer among males comprising 21% of estimated new cancer cases in 2016 in the United States (5,28). Androgens can stimulate prostate cancer growth, and lowering androgen levels through the use of androgen deprivation therapy (ADT) either chemically or surgically is a primary systemic treatment for men with locally advanced, recurrent, or metastatic disease (41). Among prostate cancer survivors (PCS), more than one-third receives ADT to reduce or eliminate testosterone, which reduces tumor androgen exposure (14,44).

The number of men prescribed ADT for prostate cancer will grow exponentially in the coming decades as worldwide aging and cancer rates escalate. Although ADT improves survival from prostate cancer, there is growing concern about both the short- and long-term adverse effects of ADT. ADT has a variety of recognized adverse metabolic effects, including obesity, insulin resistance, and lipid alterations, and also causes rapid muscle loss, which leads to decreased strength, impaired physical function, and inactivity (6,11,12,25). ADT treatment can amplify and accelerate the age-related effects of bone loss, muscle wasting, and functional decline in PCS, who are primarily older men (26,31), leading to more falls and frailty (6,12), which in turn threatens quality of life (QOL) and contributes to morbidity and mortality from noncancer causes.

Exercise is an important countermeasure to the effects of ADT treatment. Exercise is important for everyone; however, it is especially beneficial for PCS on ADT (1–4,7,18,19,32,42). It was proposed as a countermeasure to ADT adverse effects and toxicities for PCS nearly 10 yr ago (24), and it has continued to receive attention as a means to reduce the disease symptoms, improve QOL (20,34–36), and reduce disease recurrence (30). Despite the potential benefits of exercise for PCS, most men remain inactive (47), perhaps in part because there have been few attempts to broadly implement evidenced-based interventions. The objective of this systematic review was to summarize the evidence from controlled clinical exercise trials for PCS on ADT and to also describe features of efficacious programs that are relevant to consider for future implementation.

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METHODS

Protocol

PRISMA systematic review guidelines recommended by the Institute of Medicine (37) were followed, and the protocol was registered with PROSPERO international prospective registry of systematic reviews (http://www.crd.york.ac.uk/PROSPERO/, #CRD42015017348).

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Search Methods

MEDLINE®, PsycINFO, and the Cochrane database of systematic reviews were searched using medical subject headings and text words that included alternate spellings and variants of “prostatic neoplasms” OR “prostate cancer” AND “exercise” AND “patient education.” Search strategies were developed in consultation with a medical research librarian (AH) and reviewed by a second research librarian (RP). Full details of the complete search strategies for each database are available (see Supplemental Digital Content 1—complete search strategy, http://links.lww.com/TJACSM/A12). Reference lists from identified studies and review articles were manually scanned to identify any other relevant publications. No language restrictions were used in either the search or study selection. This search included publications from January 1980 through May 2016. The terms “exercise” and “physical activity” are often used interchangeably. Exercise is physical activity that is planned, structured, repetitive, and purposeful (50), whereas physical activity includes any body movement, including activities of daily living and exercise. For the purpose of this review, exercise was the intervention approach of interest because it can be specifically prescribed to target a particular system or tissue as a means to counteract the effects of disease and/or treatments. Heretofore, we will use the term “exercise” in referring to the structured interventions in this review, yet we will refer to physical activity if the exercise interventions report measurement of physical activity as an outcome.

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Inclusion Criteria and Study Selection

Randomized controlled trials (RCTs) of exercise interventions for PCS on ADT, which included a report of the amount of exercise as a measure of uptake and fidelity to the intervention, were included in this systematic review. Inclusion criteria for articles followed the PICOS (participants, interventions, comparators, outcomes, study design) framework (33). Using prespecified inclusion/exclusion criteria, two investigators reviewed titles and abstracts for potential relevance to the key questions. Three investigators reviewed and agreed on all final full-text inclusion and exclusion decisions. Trials were included only if specific exercise program prescriptions, which included time, type, and intensity of exercise, were provided to participants. If a trial only provided general advice to engage in exercise such as the encouragement to walk for 30 minutes per day, this was not considered a general physical activity program and was not considered for inclusion. Citations judged potentially relevant or unclear were carried forward to assessment of the full article. Included trials had to report at least one of the following outcome measures: fitness (i.e., cardiovascular fitness, muscular strength, or muscular endurance), body composition, fatigue, or QOL. When the same trial was published in a different article with a focus on different outcomes, relevant articles were included and considered a single intervention.

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Quality Assessment

Two reviewers independently assessed the risk of bias of the trials using the Cochrane Collaboration's Risk of Bias tool (27). Bias in the areas of random sequence generation, allocation concealment, blinding of participants or investigators, incomplete outcome data, selective outcome reporting, or other sources of bias was assessed. Each trial was given an overall summary assessment of low, high, or unclear risk of bias. Disagreements between reviewers were resolved through discussion and consensus or consultation with a third reviewer. Trials with high risk of bias were excluded.

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Data Extraction

Data were abstracted into a database and verified by a second reviewer. Prespecified data were collected for each study and included general information about the trial, methods, participants, interventions, outcomes and follow-up, study results, and adverse events.

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RESULTS

The search identified 693 unique citations. The search and selection of articles are summarized in the study flow diagram (Fig. 1). From the 693 citations, 81 were selected as possible articles for inclusion based on assessment of titles and abstracts. Full texts were reviewed for the 81 articles. Nine articles from eight RCTs (9,10,15,17,22,23,46,48,49) met the inclusion criteria for this review. Seven trials were at low risk of bias, and two had unclear risk of bias. Although there was no exclusion of articles based on language, all articles were in English. Table 1 shows selected descriptions and key outcome measures of the included trials. Because there was heterogeneity in intervention characteristics and outcome measures, no formal meta-analysis was performed.

Figure 1

Figure 1

TABLE 1

TABLE 1

From the eight RCTs included in this review, two are unique trials published by Bourke et al. (2011 publication [9] and 2014 publication [10]). The Bourke 2011 publication (9) is a feasibility pilot study of the lifestyle intervention, whereas the 2014 publication (10) report is the main trial for the same intervention. Although the two interventions are similar, the populations are different, so the trials are considered independent. Also, Galvão is the first author of two unique trials with different interventions and different populations: Galvão et al. (2010) (23) and Galvão et al. (2014) (22). To help clarify the Bourke or Galvão trials when describing results from these four trials in the text, the author name will be followed by publication year in parentheses.

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Study Characteristics

Duration of the exercise interventions ranged from 3 to 12 months. Data were collected at baseline and at the completion of the intervention for all nine studies (9,10,15,17,22,23,46,48,49). One study also collected midintervention data (48,49), and two studies collected data 6 months postintervention (9,10). One trial did not include a usual care control group but instead used a placebo. Winters-Stone et al. (48,49) compared their resistance and impact training intervention with a flexibility control group, which was not expected to influence musculoskeletal outcomes and could serve as an acceptable placebo control. This placebo control as well as the wait list control groups are included together with traditional usual care controls in this review.

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Participant Characteristics

The mean participant age in the included trials ranged from 68 to 72 yr, and the study sample sizes ranged from 50 to 155 participants, with a total of 676 participants for all trials combined. Trials included participants on ADT during the exercise intervention, with the initiation of ADT treatment varying from having received ADT a minimum of 1 yr before study participation to initiating ADT within 10 d of study enrollment, thus at the time of initiation of the intervention. All trials excluded men if they were unable to participate in exercise because of physical limitations or comorbidities, and four trials (8,9,21,46) excluded men who were currently participating in regular exercise.

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Exercise Intervention Characteristics

The exercise interventions used during these trials were heterogeneous regarding training type (resistance or aerobic), length of intervention, dose of exercise (number of exercise sessions per week), intensity of exercise, and whether training was supervised or unsupervised. Intervention characteristics are shown in Table 2. The majority of interventions dosed exercise in three sessions per week, with a range of two to six weekly sessions. Five trials used exercise interventions that included both aerobic and resistance exercise training (9,10,15,17,22,23), one with only resistance training (46) and one that used an impact (jumping) plus resistance program (48). Intervention length varied, with most being short-term programs lasting 12 wk (9,10,12,15,46) or 16 wk (17) and fewer longer programs lasting a total of 12 months with 6 months of supervised exercise followed by 6 months unsupervised exercise (22) or 12 months with only supervised exercise (48). The prescribed intensity of the exercise interventions also varied. For interventions that included an aerobic component, intensity differed in each of the trials, with a range of prescribed maximum heart rate of 55% to 85% (9,10,15,17,22,23). For trials that included resistance exercise, the amount of prescribed resistance ranged from light resistance Thera-band exercises, to 60% to 85% of one-repetition maximum (9,10,15,17), to multijoint exercises using weighted vests loaded as a percentage of body weight (22,23,46,48). The exercise interventions also differed in terms of the level of supervision provided. Three interventions included only supervised exercise sessions (15,23,46), whereas five interventions included a combination of supervised and unsupervised exercise sessions (9,10,17,22,48).

TABLE 2

TABLE 2

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Outcome Measures

All trials reported having similar groups at baseline for the current exercise or physical activity level, and measured outcomes. All trials found significant improvements favoring the intervention group over the control groups in at least one outcome measure from pre- to postintervention. Data were collected at baseline and at the completion of the intervention for all eight trials (9,10,15,17,22,23,46,48). Two trials collected data at 6 months postintervention (9,10), and one 12-month trial also collected midintervention data (48).

The identification and organization of outcome measures for this review follow the conceptual model proposed by Bennett et al. (8) regarding outcome measures in cancer exercise intervention trials. According to Bennett's model, exercise could improve physical fitness and/or reduce symptoms, and these changes in turn lead to improvements in physical function (8). Thus, measurements in reviewed trials include measures of fitness and symptoms that could underpin physical function changes. Fitness measures reported in these trials include aerobic exercise tolerance, muscular strength, and body composition. In the reviewed trials, the most commonly measured symptom was fatigue. In this model, physical function includes objective mobility, perceived mobility, and QOL. Improvement in physical function can be detected early using objective mobility measures, and when participants notice changes in their daily function, the perceived changes become apparent by self-report measures of perceived mobility and/or QOL. Objective measures of physical function in these trials include measures of walking, gait, balance, and climbing stairs. Perceived mobility is measured by self-report of difficulty in physical actions.

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Overall Findings

Seven trials reported an improvement in aerobic and strength fitness measures. Reduced fatigue was reported in four of eight trials (9,10,15,46). Each trial also reported an improvement of at least one measure of physical function (objective mobility, perceived mobility, or QOL).

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Fitness Measures

Measurement of aerobic exercise tolerance was reported in six trials (9,10,15,17,22,23), each of which included an aerobic exercise component. Significant intervention group improvements from baseline to postintervention were reported by Bourke et al. (9,10), Cormie et al. (15), and Galvão et al. (2014) (22), whereas nonsignificant findings with positive trends favoring the intervention group in the 400-m walk were reported by Galvão et al. (2010) (23) (P = 0.08), and nonsignificant differences between groups over time in the 6-min walk were reported by Culos-Reed et al. (17).

Six trials included a component of resistance exercise (9,15,22,23,46,48,49) and used measures of muscular strength as an outcome. Significant improvement from baseline to postintervention favoring the resistance exercise intervention groups in muscular strength comparing intervention with control groups was reported in each of these trials (9,15,22,23,46,48).

Body composition was measured and reported in each trial (9,10,15,17,22,23,46,48). Trials that reported significant improvements in appendicular lean mass favoring exercise groups from baseline to end of intervention are those of Cormie et al. (15) (P = 0.019), Galvão et al. (2010) (23) (P = 0.047), and Galvão et al. (2014) (22) (P = 0.019). Cormie et al. (15) found an improvement between groups over time favoring the intervention group in whole body fat mass (P = 0.001), whole body percentage fat (P < 0.001), and trunk fat mass (P = 0.008). No trials reported significant changes by the group in body weight or body mass index from baseline to postintervention.

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Symptoms

Fatigue was reported in seven trials (9,10,14,17,23,39,48). Significant positive change from baseline to end of intervention favoring the intervention group was reported in five trials: Bourke et al. (2011) (9) (P = 0.002), Bourke et al. (2014) (10) (P < 0.001), Cormie et al. (15) (P = 0.042), Galvão et al. (2010) (23), and Segal et al. (46) (P = 0.002). At 6-month follow-up postintervention, Bourke et al. (2011) (9) (P = 0.006) and Bourke et al. (2014) (10) (P = 0.007) found that significant positive changes in self-reported fatigue for the intervention groups were maintained. Galvão (2010) (23) found significant differences in baseline to 12-wk change scores (P = 0.021) for the fatigue component of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), with the exercise group improving after the intervention. Two trials reported nonsignificant findings for changes in fatigue by the group over time (14,48).

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Physical Function

Components of physical function in these trials, as in the Bennett et al. (8) model, are objective mobility, perceived mobility, and QOL. Six trials (9,15,17,22,23,48,49) measured objective mobility outcomes comparing the intervention with control groups over time. Four of those trials reported significant improvements in at least one measure of objective mobility favoring the intervention groups from baseline and postintervention (9,15,22,23). The other two trials that measured objective mobility (17,48) did not find a significant difference from baseline to posttest between the study groups. Bourke et al. (2011) (9) found positive improvements for the intervention group compared with the control group from baseline to postintervention in the chair rise test (P = 0.002), and these improvements in the intervention group were also maintained at 6-month follow-up (P = 0.001).

Significant improvement in self-report perceived mobility for the intervention group over the control group from baseline to completion of the intervention was reported by four trials (9,10,17,46). Maintenance of these significant differences was also seen at the 6-month postintervention time point for Bourke et al. (2011) (9) (P = 0.001) and Bourke et al. (2014) (10) (P = 0.038). Winters-Stone et al. (48,49) found significant improvement of self-reported physical function and disability improvement of the intervention group from baseline to postintervention with the disease-specific EORTC QLQ-C30 (P < 0.01), with disability limitation lessened more with resistance training than stretching (P = 0.018). Galvão (2010) (23) found borderline improvement of physical function of the intervention group from baseline to postintervention with the QLQ-C30 (P < 0.062).

All of the trials included a measure of health-related QOL, with three trials using the disease-specific QOL measure for prostate cancer, Functional Assessment of Cancer Therapy-Prostate (FACT-P) (9,10,46), two trials used the 36-Item Short Form Survey (SF-36) measure to assess QOL (15,22), one used the EORTC QLQ-C30 (17), and two used both the SF-36 and the EORTC QLQ-C30 (23,48). Baseline to end of intervention significant improvement of QOL between intervention and control groups in the FACT-P was reported by two trials (10,46), with no significant group differences over time reported by one (9). The SF-36 reports mixed results, with significant improvements for the intervention groups over time in some components but not others for the intervention group compared with the control group from baseline to postintervention.

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Adverse Events

Although most trials reported some adverse events, which included deaths and cardiovascular issues, none of the trials reported any of the adverse events as being directly related to the exercise interventions or testing procedures. Galvão (2014) (22) reported four individuals with adverse events due to preexisting injuries (N = 2), death from lung cancer (N = 1), and a nonfatal myocardial infarction linked to prior cardiovascular disease (N = 1). Bourke et al. (2014) (10) reported a single death in the control group and one subject in the intervention group who developed atrial fibrillation. Cormie et al. (15), Galvão (2010) (23), and Winters-Stone et al. (48,49) reported no injuries or adverse events related to participation in the exercise intervention or testing over the length of the trial. Because prostate cancer primarily affects older men, the prevalence of comorbidities also increases with advancing age, and the events described in the reviewed trials occur more often in men of this age at similar rates with or without prostate as in the interventions (39).

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Dropout and Loss to Follow-up

Dropout rates in data collected immediately postintervention ranged from 3% to 49%, with most reporting 10% to 15% dropouts (Table 2). Interventions that were 12 wk long had dropout rates (9,10,15,23,46) ranging from 3% to 23%. Cormie et al. (15) reported a 3% dropout rate in the intervention group and 23% in the control group, including 13% of the control group participants dropping out because of their desire to initiate a structured exercise program. Culos-Reed et al. (17) had a 16-wk intervention and reported a dropout rate of 21% in the intervention group and 49% in the control group. Reported reasons for dropout in Culos-Reed et al. (17) included loss to follow-up (2 in the intervention, 11 in the control), voluntary withdrawal (3 in the intervention, 6 in the control), medical reasons (5 in the intervention, 3 in the control), and unknown reasons (1 in the intervention, 3 in the control). Two trials had a 12-month intervention (22,48) and reported dropouts of 10% to 14%. Galvão et al. (2014) (22) had a 12-month intervention, of which the first 6 months was supervised with 16% dropouts in the intervention group and 10% in the control group, and for the second 6 months of home-based maintenance phase, 28% dropouts in the intervention group and 16% in the control group were reported. Winters-Stone et al. (48,49) with the intervention being 12 months in duration, had 10% dropouts in the resistance exercise group compared with 14% in the control flex group.

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Attendance at Exercise Training Classes

Reports of attendance at supervised exercise sessions range from 74% to 96% (Table 2). Across trials that used a combination of supervised and unsupervised exercise interventions, attendance at the supervised sessions was somewhat higher than compliance to unsupervised training. Bourke et al. (2011) (9) reported 95% attendance to supervised exercise sessions and attendance to unsupervised sessions at 87%. Bourke et al. (2014) (10) reported 94% attendance at the supervised exercise sessions and 82% compliance with the unsupervised sessions. Galvão et al. (2010) (23) indicated that one participant withdrew after 2 wk because he did not enjoy the program, but reported 94% attendance overall. Galvão et al. (2014) (22) reported 77% attendance of the supervised exercise sessions over the first 6 months of the intervention, but did not report compliance with the unsupervised 6-month maintenance aspect of the intervention. Segal et al. (46) reported 79% attendance at the supervised resistance exercise sessions. Winters-Stone et al. (48,49) reported 84% attendance at the supervised intervention exercise sessions compared with 43% completion of the unsupervised sessions for the intervention group.

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DISCUSSION

This systematic review provides a summary of exercise trials in PCS receiving ADT during the intervention and, given the improvement of factors that are impacted with ADT treatment, provides evidence that exercise should be considered an important component of care. Exercise for PCS receiving ADT is generally safe and was well tolerated, and in general exercise training, it improved fitness, reduced fatigue, and improved physical function. The RCT's we included showed that exercise had a significant positive effect on reversing one or more of the multiple adverse effects of ADT, reducing fatigue, and improving physical function and QOL, and it could be a valuable recommendation to ameliorate adverse treatment side effects. As expected, trials that included a component of aerobic exercise improved cardiovascular health, and trials with focus on resistance exercise improved muscular strength and endurance, and preserved lean body mass. For PCS on ADT, muscular strength and preserving lean body mass are important to overcome the treatment effect of muscle wasting.

In general, attendance at exercise sessions was quite high, with most 12-wk interventions reporting attendance at supervised sessions around 95%, with Segal et al. (46) reporting lower attendance at 79%. The 16-wk Culos-Reed et al. (17) intervention reported 78% attendance for the 1 d·wk−1 supervised session. Galvão et al. (2014) (22) is a 12-month intervention, with a combination of 6 months of supervised exercise and 6 months of unsupervised maintenance. They reported 77% attendance at the 6 months of the supervised intervention, and although participation in the unsupervised exercise program is not reported, many of the positive outcomes favoring the intervention group were maintained over the second 6 months of the intervention. The Winters-Stone et al. (48) intervention was 12 months in duration and reported 84% attendance in the supervised resistance intervention. For trials that included both supervised and unsupervised exercise intervention components, and reported participant engagement in the unsupervised components, there are differences noted in exercise program participation in the supervised components versus the unsupervised exercise component. The trials that include supervised exercise reported higher completion than unsupervised, and may benefit participants with increased social support, accountability, and positive peer pressure to attend the supervised exercise sessions (40).

In trials that included some of the exercise sessions without supervision, there was less of an increase in reported exercise and fewer positive impacts on QOL and fatigue, perhaps because of lower compliance with the unsupervised exercise program. An exception is that of Galvão et al. (2014) (22), which found positive outcomes of aerobic fitness, physical function, strength, and self-reported physical function with supervised training for the initial 6 months of intervention, followed by an unsupervised home-based maintenance phase for the next 6 months. In this trial, benefits were largely sustained despite the second 6 months of the unsupervised home-based aspect of the intervention (22). Trained professionals providing the group supervised exercise interventions may provide more of an impact for motivating and sustaining physical activity than participants receive during home-based unsupervised training.

Importantly, the exercise interventions were well received, as evidenced through high attendance rates and low rate of attrition during the intervention program implementation itself. Also, the reported reasons for withdrawal from the control groups included participants preferring to participate in the exercise interventions. Segal et al. (46) used a wait list control group for the fitness consultant one-on-one exercise sessions, and 30% of the control group requested exercise sessions at the end of the trial.

Exercise benefits are only maintained if exercise is continued; thus, maintaining exercise behaviors is an important outcome of cancer exercise interventions. Many trials only measure outcomes at baseline and at the end of the intervention. Only two of the trials (9,10) reported longer term follow-up measurements after the exercise interventions ended. Of those, Bourke et al. (2014) (10) reported durability of responses in exercise behavior at 6 months postintervention, although improvements in fatigue were not maintained. Follow-up over longer periods should be considered to measure maintenance of behaviors and longer term outcomes for exercise interventions.

Dropouts from data collection in research programs are a problem in cancer exercise trials (16). From a research perspective, loss to follow-up threatens internal and external validity. Retention of study subjects is an important aspect of behavioral intervention trials, because the strength of the study is based on the extent to which the results can be generalized to the broader population (13,43). From a health perspective, ongoing engagement in an exercise intervention is important to maximize health benefits. Additional strategies may be needed to help reduce study attrition and maintain adherence to research exercise programs (29,38).

Interventions that use supervised exercise sessions may result in more positive outcomes with better study retention. As Bourke et al. (2014) (9) reported, after withdrawal of their supervised support component, disease-specific QOL was not maintained. Interventions that work in the randomized trial setting environment may be less efficacious in real-world settings. Adherence to exercise programs and maintenance of exercise behaviors are challenges that need to be addressed.

This systematic review shows the value of exercise for PCS on ADT to reduce adverse effects of treatment and improve overall QOL. For men receiving ADT, this review reflects the importance of including resistance exercise along with aerobic fitness in an exercise program to counteract the physical and functional adverse effects of ADT and prostate cancer. There are research gaps in assessing and maintaining longer term benefits of exercise interventions for PCS on ADT, with an important consideration of home-based unsupervised exercise interventions that help PCS sustain motivation to be physically active. Continued prospective research is needed to evaluate the effects of programs incorporating resistance and aerobic exercise on treatment symptoms and QOL.

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Limitations

There are a number of limitations in this review. The interventions and outcome measures are heterogeneous, thus making it impossible to compare effects through meta-analyses. The risk of bias and quality of study is unclear in several of the trials, making it challenging to interpret outcomes with confidence. This review is not intended to be comprehensive, and there are many other important metabolic, physical, social, and mental dimensions included in these and other trials that are not included in this review. Despite these limitations, the consistency of the evidence included in these trials indicates that exercise for PCS on ADT is safe, may mitigate some of the adverse effects which impact this population, and improve physical function and QOL.

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CONCLUSIONS

Increased fitness or reductions of symptoms in the intervention group over time were reported in all trials. Improvements in physical function in the included trials were observed, as measured by objective mobility, perceived mobility, or QOL. Interventions that are both cost-effective and scalable to reach the growing population of PCS will provide valuable methods for increasing exercise and disease self-management. Further trials assessing how to convey the exercise prescriptions to survivors, sustain longer term exercise programs, maintain motivation, and implement and maintain exercise programs in real-world settings are needed.

E.M. is supported for this work by grant number K12HS022981 from the Agency for Healthcare Research and Quality.

Andrew Hamilton, Senior Reference and Instruction Librarian, OHSU Evidence-Based Practice Center and Robin Paynter, MLIS, Research Librarian, Portland VA Research Foundation, provided assistance with the development of the research strategy.

None of the authors have professional relationships with companies or manufacturers who might benefit from the results of the present study.

The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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