Prostate Cancer and Prostatic Disease (2013) 16, 328–335

& 2013 Macmillan Publishers Limited All rights reserved 1365-7852/13

www.nature.com/pcan

ORIGINAL ARTICLE
Safety and efficacy of resistance exercise in prostate cancer
patients with bone metastases
P Cormie1, RU Newton1, N Spry1,2,3, D Joseph1,2,3, DR Taaffe 1,4
and DA Galvão1

BACKGROUND: Due to concerns of fragility fracture, exercise is a perceived contraindication for prostate cancer patients with bone
metastases. These patients experience significant functional impairment and muscle atrophy, which may lead to an increased
likelihood of skeletal complications (i.e., pathological fracture, bone pain) and/or falls. Safe resistance exercise prescription may
counteract this effect. The aim of this feasibility trial was to determine the safety and efficacy of resistance exercise by prostate
cancer survivors with bone metastatic disease.
METHODS: Twenty men with established bone metastases secondary to prostate cancer were randomly assigned to a 12-week
resistance exercise program in which exercise prescription was based on the location of bone lesions (n ¼ 10) or usual care (n ¼ 10).
Outcomes included safety and tolerance of the exercise program, physical function, physical activity level, body composition,
fatigue, quality of life and psychological distress. Outcomes were compared between groups using analysis of covariance adjusted
for baseline values.
RESULTS: Participants had significant disease load with 65% of participants presenting with two or more regions affected by bone
metastases and an average Gleason score of 8.2±0.9. Five participants (exercise ¼ 2; usual care ¼ 3) did not complete the
intervention, three of which were due to advancing disease (exercise ¼ 2; usual care ¼ 1). No adverse events or skeletal
complications occurred during the supervised exercise sessions. The exercise program was well tolerated as evidenced by high
attendance (83%) and compliance rates (93%), and the ability of the participants to exercise at an intensity within the target range
for cancer survivors (rating of perceived exertion ¼ 13.8±1.5). The change in physical function (muscle strength B11%;
submaximal aerobic exercise capacity B5% and ambulation B12%), physical activity level (B24%) and lean mass (B3%) differed
significantly between groups following the intervention, with favorable changes in the exercise group compared with the usual
care group. No significant between-group differences were observed for fatigue, quality of life or psychological distress.
CONCLUSIONS: This initial evidence involving a small sample size suggests that appropriately designed and supervised resistance
exercise may be safe and well tolerated by prostate cancer patients with bone metastatic disease and can lead to improvements in
physical function, physical activity levels and lean mass. Future trials involving larger sample sizes are required to expand these
preliminary findings.

Prostate Cancer and Prostatic Disease (2013) 16, 328–335; doi:10.1038/pcan.2013.22; published online 6 August 2013
Keywords: bone metastatic disease; physical activity; advanced cancer; physical function

INTRODUCTION strategies to reduce the burden of bone metastatic disease have

Bone metastatic disease is estimated to affect 65–75% of a high degree of clinical importance.
men with prostate cancer1 and involves sclerotic lesions that Clinical trials have demonstrated exercise to be an effective
commonly occur in the axial skeleton and pelvis.2 Although the medicine to counteract treatment-related adverse effects, leading
clinical course of bone metastatic disease secondary to prostate to improved physical and psychological outcomes in men with
cancer is relatively long with an estimated 5-year survival rate of localized prostate cancer.13,14 The magnitude of effect observed in
30–46%,1,3 it is associated with significant morbidity caused by studies involving prostate cancer patients as well as patients with
skeletal complications.1,4 As such, patients are likely to experience other cancer diagnoses (predominately breast cancer) has led the
bone pain, pathological fractures, hypercalcaemia and spinal American Cancer Society to endorse international guidelines that
cord/nerve compressions over an extended period of time.1,4,5 advise all cancer survivors (including those with bone metastases)
These complications coupled with the extensive treatment- to avoid inactivity and engage in regular exercise including
related adverse effects of long-term androgen-suppression strength training exercises.15,16 However, there is an absence
therapy6–9 and therapy for castration-resistance disease1,10 result of clinical trials examining whether exercise is safe and can be
in considerable disease burden that has a profound impact tolerated by patients with bone metastatic disease. In fact, all
on everyday function and quality of life.4,11,12 Consequently, clinical trials to date investigating the safety and efficacy of

1
Edith Cowan University Health and Wellness Institute, Edith Cowan University, Joondalup, Western Australia, Australia; 2Department of Radiation Oncology, Sir Charles Gairdner
Hospital, Nedlands, Western Australia, Australia; 3Faculty of Medicine, University of Western Australia, Nedlands, Western Australia, Australia and 4School of Environmental and
Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia. Correspondence: Dr P Cormie, Edith Cowan University Health and Wellness Institute, Edith Cowan
University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.
E-mail: [email protected]
Received 9 May 2013; revised 30 May 2013; accepted 26 June 2013; published online 6 August 2013
 Exercise for patients with bone metastases
P Cormie et al
329
exercise have excluded patients who had bone metastases or diagnosis of prostate cancer, established bone metastatic disease as
bone lesions deemed as unstable due to the potential increased determined by a whole-body bone scan and obtained written medical
risk of skeletal complications.17 Although reasonable given the clearance from their physicians (general practitioner). Patients were
relative paucity of research into the safety and efficacy of exercise excluded if they experienced moderate–severe bone pain that limited
in the general oncology setting, this situation is highly detrimental activities of daily living (i.e., National Cancer Institute’s Common
Terminology Criteria for Adverse Events grade 2–3 bone pain19) or had
because patients with bone metastases are reducing their physical musculoskeletal, cardiovascular and/or neurological disorders that could
activity levels for fear of skeletal complications, a strategy that inhibit them from exercising (as determined by the patient’s physician).
can only result in further declines in musculoskeletal structure and This protocol was approved by the University Human Research Ethics
function, a greater risk of comorbid conditions and a reduced Committee and all participants provided written informed consent.
quality of life.5,11,18 Safe exercise prescription for prostate cancer
patients with bone metastatic disease may provide clinically
meaningful benefits to patients through improvements in Experimental design
musculoskeletal structure/function, which lead to enhanced This pilot study involved a two-armed prospective randomized controlled
functional abilities and potentially a reduced risk of skeletal trial design. Following familiarization and baseline testing sessions,
participants were randomized into the two arms: exercise or usual care.
complications. Despite the likely benefit of targeted exercise Stratification for age (p704) was carried out and participants were
prescription for patients with bone metastatic disease, there is a randomized in an allocation ratio of 1:1 using a random assignment
clear lack of clinical and empirical data of implementing exercise computer program. The project coordinator and exercise physiologists
in these advanced patients. The purpose of this trial was to involved in assigning participants to groups were blinded to the allocation
provide initial experimental data on safety and efficacy of resis- sequence. Participants randomized to the usual care group received no
tance exercise in prostate cancer survivors with bone-metastatic intervention but were offered the exercise program after the completion
disease. To the authors’ knowledge, this is the first trial specifically of the intervention period. All participants were instructed to maintain
designed to examine exercise in cancer patients with bone their customary activities, dietary and social patterns as well as their usual
metastases. self-management regimen throughout the intervention period.

Exercise intervention
MATERIALS AND METHODS The exercise intervention involved twice-weekly resistance exercise
Participants sessions for 12 weeks in an exercise clinic. Sessions were conducted in
Twenty-seven men aged 57–83 years with bone metastatic disease small groups of one to five participants supervised by accredited exercise
secondary to prostate cancer were referred by oncologists and urologists physiologists. The sessions were B60 min in duration, commencing with
in Perth, Western Australia from July 2011 through July 2012 and screened a 5-min warm-up period and ending with a 10-min cool-down period
for participation in the study (Figure 1). Participants had a histological consisting of low-level aerobic exercise and stretching. The resistance

Directly referred by oncologists and

assessed for eligibility (n= 27)

Excluded (n = 7)
• Declined to participate (n = 5)
• Not interested (n = 3)
• Health concerns (n = 2)
• Other reasons (n = 2)
• Too far to travel (n = 2)

Randomized (n = 20)

Allocated to Exercise (n = 10) Allocated to Usual Care (n = 10)

Discontinued intervention (n = 2) Lost to follow-up (n = 3)

• Further treatment (chemotherapy) = 1 • Further treatment (chemotherapy) = 1
• Increased bone pain (during 2 week break • Too far to travel = 1
from intervention over holiday) = 1 • Became carer for wife = 1

Analysed (n = 10) Analysed (n = 10)

• Missing data for 400 meter walk (n = 4) • Missing data for 400 meter walk (n = 1)
and leg extension 1RM (n = 4) due to and leg extension 1RM (n = 1) due to
femur bone metastases & knee femur bone metastases for baseline and
osteoarthritis for baseline and 12 weeks 12 weeks

Figure 1. Flow of participants throughout the trial. RM, repetition maximum.

& 2013 Macmillan Publishers Limited Prostate Cancer and Prostatic Disease (2013), 328 – 335
 Exercise for patients with bone metastases
P Cormie et al
330
sessions attended. Non-compliance to an exercise session was considered
Table 1. Systematic approach to resistance exercise selection for as any deviation from the prescribed number of exercises, sets or
prostate cancer with bone metastases repetitions (for example, a session was classified as non-compliant if just
one set of one exercise was not completed). Session rating of perceived
Metastases site Body region to target exertion (RPE) was recorded immediately after the completion of each
exercise session to assess the perceived intensity of the exercise.25
Upper body Trunk Lower body Participants were asked to rate the overall difficulty of the session (i.e., how
hard/how much exertion was involved) on a scale of 6 (no exertion at all)
Pelvis O O Ob to 20 (maximal exertion). A 7-point Likert scale was also administered after
the completion of each exercise session to assess the perception of
Lumbar spine O — O
tolerance of the exercise session.26 Participants rated how much they
Thoracic spine and/or ribs Oa — O agreed or disagreed to the statement ‘‘I have found the exercise session to
Femur O O Ob be tolerable’’ on a scale of one (strongly disagree) to seven (strongly
agree).
All regions O a
— Ob
O ¼ Target exercise region. Physical function and physical activity levels. A series of standard tests
a
Exclusion of shoulder flexion/extension/abduction/adduction; inclusion of were used to assess physical function that are as follows:21 (1) one RM in
elbow flexion/extension. the leg extension (muscular strength), (2) 400-m walk (submaximal aerobic
b
Exclusion of hip extension/flexion; inclusion of knee extension/flexion. exercise capacity), (3) usual and fast pace 6-m walk (ambulation), (4) timed
up and go (muscular power and ambulation) and (5) sensory organi-
zation test (balance) performed on the Neurocom Smart Balancemaster
exercise regime included eight exercises that target the major muscle (NeuroCom, Clackamas, OR, USA). To minimize the potential risk of skeletal
groups of the upper and lower body. The selection of specific exercises complications, participants with bone metastases affecting the femur
was based on the location of bone metastases so that affected regions did not perform the 400-m walk and leg extension 1RM assessments
were not targeted and mechanical force was minimized (Table 1).20 (exercise group n ¼ 3; usual care group n ¼ 1). Falls self-efficacy was
Participants were instructed to perform the exercises using controlled, also determined using the Activities-Specific Balance Confidence scale
smooth movements at a set cadence of 1–2 s for both eccentric (ABC score; higher score represent greater balance confidence).27 Physical
and concentric phases in order to minimize peak forces transmitted activity levels were assessed objectively over a 7-day period using a
to the skeleton. The resistance exercise load progressed from 12–8 validated, reliable tri-axial accelerometer activity monitor (ActiGraph
repetition maximum (RM) with two to four sets per exercise.16,21 GT3X þ ).28 The assessment period occurred prior to baseline testing
To ensure the progressive nature of the program, participants were and after the completion of the post-intervention test (i.e., not
encouraged to work past the specific RMs prescribed and if they contaminated by exercise sessions and/or testing sessions involved
exceeded the target then additional resistance was added for the next with the trial). Standard data processing was applied and the weekly
set and/or session. The prescribed target number of RM (i.e., 12–8 RM) duration of low, moderate and vigorous-intensity physical activity
and sets (i.e., 2–4) were progressed every 2 weeks, with the absolute determined in accordance with established ranges.29 Self-reported
load of each exercise progressed according to individual response. physical activity was also assessed by the leisure score index from the
Although the intensity and volume of the resistance exercise program is Godin Leisure-Time Exercise Questionnaire.30,31
in accordance with recommendations for cancer patients with localized
disease,16 the modular approach to exercise selection involved Body composition. Regional and whole-body lean mass and fat mass
with this program is novel and specialized for patients with bone were derived from whole-body dual-energy X-ray absorptiometry scans
metastatic disease.20 This approach is designed to minimize compressive (Hologic Discovery A, Waltham, MA, USA). Appendicular lean mass, trunk
and shear loads on affected skeletal sites to account for the reduced adiposity and visceral fat mass were assessed using standard procedures.
load-bearing capabilities of the bone because of metastatic disease
in specific regions. Participants were encouraged to supplement the
resistance exercise sessions with home-based aerobic exercise sessions Patient-reported outcomes. A series of questionnaires with sound
involving walking and/or stationary cycling, with the aim of accumulating psychometric properties were utilized to assess cancer-related fatigue,
a total of at least 150 min of moderate-intensity aerobic exercise each quality of life and psychological distress. The Multidimensional Fatigue
week.16 Symptom Inventory-Short Form assessed general, physical, emotional,
mental and total fatigue as well as vigor.32 The Medical Outcomes Study
36-Item Short-Form Health Survey (SF-36) was used to assess quality of life
Outcome measures status across the following domains: physical function, role physical, body
Outcome measures were assessed at baseline (0 weeks) and post pain, general health, vitality, social function, role emotional and mental
intervention (12 weeks). Participants completed a familiarization session health.33 The Brief Symptom Inventory-18 was utilized to assess psycho-
7–10 days prior to baseline testing involving all physical function logical distress across the domains of depression, anxiety, somatization
assessments. and global distress severity.34

Safety and tolerability of exercise. The safety of the exercise program was
assessed by recording the incidence and severity of any adverse events Statistical analyses
and skeletal complications (including pain at known bone metastases sites Sample size calculations were based on change in physical function.
and pathological skeletal fractures1) throughout the intervention. Any As the first exercise intervention trial involving patients with bone
adverse event occurring during a supervised exercise session was recorded metastatic disease, we estimated the change in physical function
by the exercise physiologist and events occurring outside of the based on results over the same intervention period in prostate cancer
supervised sessions were recorded using a detailed log completed by patients with localized disease.21 We anticipated a change of 10% with a
the participant. Severity of bone pain was assessed using the Functional s.d. of 8% for an effect size of 1.25. With an alpha level of 0.05 and a
Assessment of Cancer Therapy Bone Pain questionnaire, with higher scores final sample of 20 patients, we achieved 75% statistical power to detect
representing lesser bone pain and/or better quality of life,22,23 as well as a such a change.
visual analog scale (VAS)24 including severity ratings from no pain (VAS Data were analyzed using SPSS Statistics 20. Analyses including standard
score ¼ 0) to very severe pain (VAS score ¼ 10). Additional measurements descriptive statistics, independent t-tests, w2 tests, analysis of covariance
were taken during every exercise session. The level of bone pain adjusted for baseline values. Measures of bone pain were also adjusted
participants were experiencing prior to the start of each exercise session for use of pain medication. An intention-to-treat approach was utilized
was assessed using the VAS. Participants designated the location of any for all analyses using maximum likelihood imputation of missing values
bone pain and whether this pain affected their ability to undertake usual (expectation maximization). All tests were two-tailed, with statistical
activities of daily living since the previous exercise training session. significance set at an alpha level of 0.05. Results are presented as
Compliance to the prescribed exercise program was assessed as the rate of mean±s.d. or number of participants (percentage of participants) for
successfully completed exercise sessions compared with the number of frequency data.

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 Exercise for patients with bone metastases
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Table 2. Baseline characteristics of participants

Baseline variables Exercise (n ¼ 10) Usual care (n ¼ 10) P-value

Age (years) 73.1±7.5 71.2±6.9 0.565

Height (cm) 173.5±8.2 170.2±8.6 0.390
Weight (kg) 87.4±10.3 82.4±14.8 0.386
BMI (kg/m2) 29.1±3.1 28.3±4.0 0.644
Number of comorbiditiesa 1.7±1.3 1.5±1.1 0.717
Number of medications 3.6±1.8 5.3±3 0.143
Tertiary education 2 (20) 2 (20) 1.000
Married 8 (80) 9 (90) 0.531
Current smoker 0 (0) 0 (0) 1.000
Time since cancer diagnosis (years) 3.9±3.8 4.9±2.9 0.507
Self-rated healthb 3.2±0.9 2.8±0.6 0.272

Physical activity level (min/week)c 59.2±76.3 91.0±88.2 0.400

Meet guidelines (X150 min/week) 2 (20) 4 (40) 0.631
Insufficient activity (o150 min/week) 3 (30) 2 (20)
Sedentary (0 min/week) 5 (50) 4 (40)

Gleason score 8.4±0.7 8.0±1.1 0.352

Time since bone metastatic disease diagnosis (years) 1.0±1.1 1.0±1.0 0.473

Location of bone lesions

Pelvis 9 (90) 7 (70) 0.264
Lumbar Spine 7 (70) 5 (50) 0.361
Ribs/Thoracic Spine 6 (60) 6 (60) 1.000
Femur 3 (30) 1 (10) 0.264
Other 4 (40) 3 (30) 0.639

Severity of bone metastatic disease 0.656

Minor (one region affected) 3 (30) 4 (40)
Moderate (two regions affected) 2 (20) 3 (30)
Major (more than two regions affected) 5 (50) 3 (30)
Number of regions affected 3.1±2.0 2.3±1.4 0.320
Using pain medication 3 (30) 1 (10) 0.264
Bone pain (VAS) 0.3±0.4 0.5±0.7 0.416
(range: 0.0–1.1) (range: 0.0–2.1)
Previous AST 10 (100) 10 (100) 1.000
Previous radiation 6 (60) 5 (50) 0.653
Previous surgery 1 (10) 3 (30) 0.264
Abbreviations: AST, androgen-suppression therapy; BMI, body mass index; Gleason score, 0–10; VAS, visual analog scale.
Results presented as mean±s.d. or number of participants (percentage of participants).
a
Cardiovascular disease, hypertension, diabetes, osteoporosis and dyslipidemia.
b
Self-rated health—1 ¼ excellent, 2 ¼ very good, 3 ¼ good, 4 ¼ fair and 5 ¼ poor.
c
Self-reported physical activity level from the Godin Leisure-Time Exercise Questionnaire.31

RESULTS Safety and tolerability of exercise

The two groups were well balanced, with no significant differences No adverse events or skeletal complications occurred during the
in characteristics at baseline (Table 2). Furthermore, there were exercise sessions (Table 3). One incident was reported outside of
no significant differences between groups at baseline in any the exercise sessions, in which a participant in the exercise group
of the outcome measures assessed. Participants had significant fell while dressing at home and suffered a fractured rib. This
disease load, with 65% of participants presenting with two or more occurred during week 10 of the intervention; however, he was
regions affected by bone metastases and an average Gleason score able to continue the intervention with a modified exercise
of 8.2±0.9. Two participants from the exercise group discontinued program for the remaining 2 weeks. There was no between-
the intervention because of advancing disease requiring further group difference in the total number of adverse events that
treatment with chemotherapy (n ¼ 1) and increased level of occurred throughout the intervention period (exercise ¼ 3 (advan-
bone pain which occurred during a 2-week break from the exercise cing disease requiring chemotherapy ¼ 1, increased bone pain ¼ 1
program over the Christmas holiday period (n ¼ 1; related to and fall ¼ 1); usual care ¼ 1 (advancing disease requiring chemo-
events outside of the intervention). Three participants from the usual therapy); P ¼ 0.264). There was no change in the use of pain
care group were lost to follow-up because of advancing disease medication throughout the intervention. Exercise program atten-
requiring further treatment with chemotherapy (n ¼ 1), dance was high, with an average attendance of 20 sessions out
travel constraints (n ¼ 1) and the need to commit to being a full- of a possible 24 (83% attendance) and 70% of the participants
time carer for their spouse (n ¼ 1). There were no demographic or completing all the 24 sessions. Compliance to the exercise
clinical differences between those who did and did not prescription was 93.2±6.3% (i.e., 93% of attended sessions were
complete the intervention. Four participants from the usual care successfully completed in full adherence with the prescribed
group completed the delayed exercise program after the interven- program). Deviations from the prescribed program commonly
tion period and the outcomes were similar to those of the involved not completing all the required sets for an exercise or not
exercise group. performing an exercise during the session. There were no

& 2013 Macmillan Publishers Limited Prostate Cancer and Prostatic Disease (2013), 328 – 335
 Exercise for patients with bone metastases
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332
Table 3. Safety and tolerability of the exercise intervention

Measure Result

Adverse events during the exercise sessions 0

Attendance (out of 24 sessions) 20.2±7.6
Compliance (% of successfully completed sessions out of number of sessions attended) 93.2±6.3
Perceived exercise intensity (session RPE) 13.8±1.5
Perceived tolerance of the exercise sessions (0 ¼ intolerable; 7 ¼ highly tolerable) 6.1±0.7

Severity of bone pain at the start of each session (VAS; 0 ¼ no pain; 10 ¼ very severe pain)
Average of all sessions 0.6±0.7
Maximum across all sessions 1.4±1.2
Range across all sessions 1.3±1.1
Incidence of bone pain negatively affecting the ability to undertake usual activities of daily living between exercise sessions 0
Abbreviations: RPE, rating of perceived exertion (target range for cancer survivors is 12–16, which is equivalent to descriptors of between ‘light and somewhat
hard’ to between ‘hard (heavy) and very hard’); VAS, visual analog scale.
Results presented as number of incidents or mean±s.d.

significant group differences in the change in bone pain following DISCUSSION

the intervention (Table 4). The severity of bone pain reported at
each exercise session was low, with an average of 0.6±0.7 on a This trial provides initial evidence that appropriately designed and
scale of 0 (no pain) to 10 (very severe pain) and a maximum of supervised resistance exercise may be safe and effective in
1.4±1.2 across all sessions (Table 3). The highest level of bone prostate cancer patients with bone metastatic disease. The
pain recorded throughout the exercise program was 3.3. There primary findings were that appropriate resistance exercise
were no incidences in which a change in bone pain since the prescription (1) was well tolerated and did not significantly
previous exercise session negatively affected the abilities to increase skeletal complications and (2) resulted in improved
undertake normal daily activities (Table 3). Participants were able physical function, physical activity levels and lean mass in the
to exercise at an intensity within the target range for cancer sample of prostate cancer patients with bone metastases involved
survivors (i.e., moderate–high intensity; RPE ¼ 12–1616) with the in this trial.
average perceived intensity of 13.8±1.5 on the RPE scale. International exercise guidelines for cancer survivors recom-
Furthermore, the exercise sessions were well tolerated as mend an ‘altered’ program for patients with bone metastases due
evidenced by an average perceived tolerance score of 6.1±0.7 to increased risk of skeletal complications.16 However, no evidence
out of a possible rating of 7 (Table 3). has been available to support or refute this claim or to provide any
guidance on the alterations in exercise prescription necessary for
this patient population. This trial provides the first evidence to
Physical function and physical activity levels address this gap in knowledge. Specifically, appropriately
supervised resistance exercise targeting areas unaffected by
Change in maximal muscular strength (leg extension 1RM B11%;
bone metastases was observed to be safe and well tolerated by
n ¼ 16), submaximal aerobic exercise capacity (400-m walk B5%;
this cohort of prostate cancer patients with bone metastatic
n ¼ 16) and ambulation (6-m walk—usual pace B12%) across the
disease. Despite the high disease load associated with the enrolled
12-week intervention differed significantly between groups, with
participants, no adverse events were observed during the exercise
favorable changes in physical function observed for the exercise
sessions and there were no between-group differences in the
group compared with the usual care group (Table 4). Trends
number of adverse events that occurred throughout the 12-week
towards greater improvement in the exercise group for 6-m
intervention period. Importantly, the patients involved in this trial
walk—fast pace (B7%)— and timed up and go (B6%)
were able to exercise at intensities required to realize health
performance were also observed. No significant between-group
benefits (i.e., moderate–high intensity) consistently throughout
differences were observed for balance or balance confidence
the program.15,16
(Table 4). Change in low-intensity physical activity level across the
Not only was the targeted resistance exercise program safe but
12-week intervention differed significantly between groups
was also effective, resulting in improvements to musculoskeletal
(B24%), with the exercise program prompting favorable physical
structure and function in this sample of patients. Despite a
activity behavior compared with usual care (Table 4). A borderline
relatively short intervention, the exercise program resulted in
group difference in the change in vigorous-intensity physical
significant improvements in muscular strength (B11%), submax-
activity was also observed.
imal aerobic exercise capacity (B5%) and ambulation (B12%),
changes anticipated to have a considerable impact on functional
ability in everyday life.35 Notably, the program protected against
Body composition
muscle atrophy with an B4% difference in the change in lean
Change in whole body and appendicular lean mass across the muscle mass observed between the exercise and usual care
12-week intervention differed significantly between groups (B3 groups. Collectively, these improvements have a high degree of
and 4% respectively; Table 4). Favorable changes were observed clinical significance, as they protect against falls and skeletal
for the exercise group compared with the usual care group. No complications that cause significant morbidity and mortality36–38
significant between-group differences were observed for fat mass as well as high treatment costs.39 Although fat mass was not
(Table 4). reduced by this short-duration exercise intervention, the increase
in skeletal muscle mass will likely result in considerable benefit by
ameliorating metabolic disorders through improved insulin
Patient-reported outcomes resistance and glucose homeostasis.40 Furthermore, the exercise
No significant between-group differences were observed for intervention had a positive effect on objectively measured
fatigue, quality of life or psychological distress (Table 5). levels of physical activity (beyond the prescribed exercise

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 Exercise for patients with bone metastases
P Cormie et al
333
Table 4. Bone pain, physical function, physical activity levels and body composition values and the group difference in change over the intervention

Measure Baseline 12 Weeks Adjusted group differences in mean

change over 12 weeksa

Exercise Usual care Exercise Usual care Mean 95% CI P

Mean s.d. Mean s.d. Mean s.d. Mean s.d.

Bone pain
FACT-Bone Pain 53.8 4.5 50.1 9.0 50.7 4.5 52.3 5.5  2.5  7.0 2.0 0.262
(score)b
Bone Pain—VAS 0.3 0.4 0.5 0.7 0.9 1.2 0.8 1.6 0.3  0.9 1.5 0.602
(cm)b

Physical function
Leg extension 1RM 76.2 17.6 71.4 23.5 80.3 16.7 68.7 21.4 7.9 1.8 14.0 0.016
(kg)
400-m Walk 252.1 40.8 280.8 53.0 246.9 32.9 286.5 50.5  13.7  23.5  3.9 0.010
(seconds)
6-m Walk—usual 4.48 0.54 4.45 0.56 4.23 0.33 4.76 0.42  0.55  0.78  0.32 o0.001
pace (seconds)
6-m Walk—fast pace 3.21 0.49 3.20 0.71 3.16 0.40 3.37 0.63  0.21  0.44 0.02 0.070
(seconds)
Timed up and go 7.41 1.50 7.59 1.91 6.97 1.02 7.32 1.17  0.42  1.00 0.12 0.150
(seconds)
Balance—SOT (score) 76.2 7.2 73.8 8.7 75.3 8.0 74.1 7.4  1.0  3.4 1.3 0.362
Balance confidence 79.2 26.6 87.5 16.4 80.8 24.6 84.6 20.5 2.4  13.2 17.8 0.752
(ABC score)

Physical activity level (accelerometer)

Low intensity 341.7 143.3 359.6 140.7 356.7 112.6 316.8 121.4 82.5 31.8 133.2 0.003
(min/week)
Moderate intensity 179.6 143.2 167.1 91.0 165.4 139.8 147.7 90.5 25.4  18.1 68.9 0.233
(min/week)
Vigorous intensity 1.8 2.8 2.8 4.1 1.7 2.3 0.7 0.6 1.6 0.0 3.2 0.053
(min/week)
Godin Leisure Score 18.5 17.2 22.5 20.1 26.2 28.8 24.6 18.5 5.9  7.2 19.1 0.353
Indexc

Body composition (DXA)

Whole body lean 57.2 7.8 53.2 9.7 57.8 8.0 52.5 8.0 1.7 0.2 3.2 0.026
mass (kg)
Appendicular lean 24.3 3.7 21.4 3.9 24.5 3.7 20.9 3.3 1.0 0.4 1.6 0.003
mass (kg)
Whole body fat mass 27.7 5.6 27.2 5.7 27.8 6.0 27.5 6.5  0.3  1.4 0.9 0.642
(kg)
Trunk fat 14.7 3.4 15.0 3.4 14.6 3.7 15.0 3.8 0.0  0.6 0.6 0.946
mass (kg)
Whole body percent 31.7 4.9 32.7 2.2 31.5 5.1 33.0 3.3  0.4  1.9 1.2 0.627
fat (%)
Visceral fat 0.89 0.20 0.96 0.19 0.89 0.23 0.96 0.19 0.01  55.3 58.6 0.951
mass (kg)
Abbreviations: ABC, Activities-Specific Balance Confidence scale; DXA, dual energy X-ray absorptiometry; FACT, Functional Assessment of Cancer Therapy;
1RM, one repetition maximum; SOT, sensory organization test; VAS, visual analog scale.
a
Between-group change by ANCOVA adjusted for baseline values.
b
Includes adjustment for use of pain medication.
c
Derived from self-report not from accelerometer data.
Bold values show Po0.05.

intervention), prompting behavior change that led to a difference the safety and efficacy of the intervention. However, limitations
of B24% between exercisers and non-exercisers. This is included the low number of participants involved with the trial,
another clinically meaningful outcome, given the association the relatively well-functioning status of the participants, the self-
between physical activity and both all-cause and prostate cancer reporting approach to monitor the severity of bone pain and
mortality.14 adverse events outside of supervised exercise sessions, as well as
There are several unique features of this research that are the lack of a follow-up assessment point. The number of
worthy of comment. This trial was the first to specifically target participants restricted the power to detect significant changes in
patients with bone metastatic disease and involved older patients outcomes with small–moderate standardized effects (i.e., quality
with high disease load; a cohort that is typically difficult to enroll of life, psychological distress and fatigue). Further research
in exercise trials. Furthermore, a thorough series of objective and involving larger sample sizes and the combination of resistance
self-reported measures were used to comprehensively examine and aerobic exercise within the supervised exercise program is

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Table 5. Absolute and change values for patient-reported outcomes of fatigue, quality of life and psychological distress

Measure Baseline 12 Weeks Adjusted group differences in

mean change over 12 weeksa

Exercise Usual care Usual care Exercise Mean 95% CI P

Mean s.d. Mean s.d. Mean s.d. Mean s.d.

Fatigue (MFSI-SF)
Total (score) 5.2 16.8 6.0 12.3 3.8 13.7 8.8 24.9  4.2  17.6 9.2 0.521
General (score) 7.0 6.2 7.1 4.8 6.1 3.3 9.1 7.4  2.9  7.6 1.7 0.199
Physical (score) 3.1 3.0 3.4 2.5 2.3 1.7 2.4 2.7 0.0  1.8 1.9 0.961
Emotional (score) 3.5 3.7 3.3 3.0 4.2 4.2 3.4 6.5 0.5  3.1 4.1 0.772
Mental (score) 4.3 3.2 4.6 3.8 4.8 2.6 6.7 6.5  1.5  4.3 1.3 0.261
Vigor (score) 12.7 4.5 12.4 2.5 13.3 5.5 13.1 5.7  0.1  3.4 3.2 0.931

Quality of life (SF-36)

Physical Functioning (NBS) 44.2 9.0 45.0 11.4 45.8 7.8 46.5 9.4 0.0  4.2 4.2 0.996
Role Physical (NBS) 42.9 11.5 40.7 10.8 44.7 8.1 43.4 11.1 0.0  7.2 7.2 0.998
Bodily Pain (NBS) 48.8 8.8 49.7 10.7 45.4 8.7 48.8 8.7  2.8  9.1 3.5 0.356
General Health (NBS) 45.6 10.0 42.4 8.6 44.5 9.8 41.7 8.6 1.9  4.1 7.9 0.508
Vitality (NBS) 45.8 12.7 49.3 11.3 46.1 9.1 44.5 11.9 3.7  3.7 11.1 0.303
Social Functioning (NBS) 41.1 7.5 38.1 9.4 43.5 5.4 40.2 10.3 2.2  5.3 9.7 0.550
Role Emotional (NBS) 37.8 8.9 36.6 9.0 34.8 10.3 37.2 11.5  3.2  12.3 5.8 0.461
Mental Health (NBS) 50.6 10.4 50.6 7.9 52.9 8.1 50.7 13.7 2.2  6.1 10.6 0.578
Physical Health Composite 45.2 11.2 45.1 10.2 45.8 8.5 45.9 9.1  0.1  4.6 4.4 0.957
Mental Health Composite 44.1 10.1 43.5 7.2 43.9 11.4 42.6 12.9 2.8  5.3 11.0 0.475

Psychological distress (BSI  18)

Depression (score) 2.9 4.0 1.4 2.1 3.7 6.1 3.7 5.7  2.3  5.2 0.6 0.107
Anxiety (score) 1.7 1.8 1.5 2.0 2.7 3.2 3.3 5.5  1.0  3.8 1.8 0.471
Somatization (score) 2.3 2.4 2.3 3.2 2.8 2.5 1.9 2.0 1.0  1.1 3.0 0.346
Global Severity Index (score) 6.9 6.2 5.2 5.6 9.2 11.4 9.2 12.8  3.0  9.2 3.1 0.311
Abbreviations: BSI-18, Brief Symptom Inventory; MFSI-SF, Multidimensional Fatigue Symptom Inventory-Short Form; NBS, norm-based score; SF-36, Medical
Outcomes Study 36-Item Short-Form Health Survey.
a
Between-group change by ANCOVA adjusted for baseline values.

underway to expand these initial findings and also to determine larger sample sizes are required to expand these preliminary
whether exercise confers any beneficial effect on quality of life in findings.
patients with bone metastases.20 Despite their significant disease
load, participants were relatively well-functioning individuals
(i.e., average self-rated health reported as ‘good’; Table 2) who CONFLICT OF INTEREST
were mostly motivated to undertake the exercise study. Thus, they The authors declare no conflicts of interest.
may not be representative of all prostate cancer patients with
bone metastatic disease, and the results of this trial should be
interpreted with this in mind. Furthermore, future trials involving
long-term follow-ups are required to examine whether exercise ACKNOWLEDGEMENTS
has a protective effect against the risk of skeletal complications, This study was funded by the Cancer Council of Western Australia through the Early
disease progression and ultimately mortality. Career Investigator research grants program. PC is supported by the Cancer Council
Western Australia Postdoctoral Research Fellowship. DAG is funded by a Movember
New Directions Development Award obtained through the Prostate Cancer
Foundation of Australia’s Research Program.
CONCLUSIONS
Exercise programs for patients with bone metastases must be
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