Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial
Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the 'FC Prostate' randomized controlled trial
Jacob Uth 1
Jakob Friis Schmidt
Jesper Frank Christensen 1
Lars Juel Andersen
Peter Riis Hansen
Karl Bang Christensen
Lars Louis Andersen
Eva Wulff Helge
Julie Midtgaard 0 1
0 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, Copenhagen 2200 , Denmark
1 The University Hospitals Centre for Health Care Research (UCSF), Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, Copenhagen 2100 , Denmark
Background: Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The 'Football Club (FC) Prostate' study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design: Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2-3 times/week for 45-60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion: The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration: ClinicalTrials.gov: NCT01711892
Prostate cancer; Androgen deprivation therapy; Physical exercise; Soccer training; Rehabilitation; Body composition; Cardiovascular function
Prostate Cancer (PCa) is the most common
noncutaneous malignancy in men, with 650,000 estimated
new cases per year in the developed world . Androgen
deprivation therapy (ADT) remains a cornerstone of
PCa management, with approximately 50% of men
diagnosed with PCa undergoing ADT at some point in time
. ADT is administered with curative intent before and
23 years after radiotherapy for locally advanced disease
, or as continuous palliative treatment for
disseminated disease . The 15 year relative survival rate now
exceeds 90% for all PCa stages combined and there has
been a steady increase in the number of PCa survivors
, partly attributable to the greater anti-neoplastic
efficacy of ADT and radiotherapy in combination.
While ADT contributes to improved life expectancy, it
is also associated with significant adverse effects, including
loss of lean body mass (LBM), decreased bone mineral
density (BMD), poor functional performance, increased
fat percentage, insulin resistance, and increased risk of
fractures [6-10]. The combination of ADT-induced
adverse effects and subsequent changes in health behavior,
i.e., physical inactivity and deconditioning, may predispose
PCa patients to serious morbidity, including elevated risk
of cardiovascular and metabolic disorders, leading to
increased mortality [11,12]. Therefore, interventions aimed
at counteracting ADT-induced adverse effects may result
in profound survival benefits for patients with PCa.
Physical exercise is emerging as a promising
supplementary treatment strategy in the oncology setting, with
capacity to improve aerobic fitness, muscle strength,
body composition, quality of life (QoL) and physical
function, and to reduce fatigue [13,14]. Indeed, such
improvements have been reported after physical exercise in
studies of PCa patients undergoing ADT. Galvo et al.
found that 12 weeks of combined resistance and aerobic
training improved muscle mass, muscular strength,
physical function and balance . In agreement with
these results, Segal et al.  found that a 24 week
program of aerobic exercise combined with resistance
training mitigated fatigue and maintained aerobic fitness in
PCa patients undergoing radiotherapy with or without
concurrent ADT. Although data from these and other
randomized controlled trials (RCTs) [17-19] suggest that
physical exercise interventions have considerable
potential in counteracting treatment-related side-effects,
important questions remain unanswered. First, the
duration of interventions to date has been relatively brief
(i.e., 12 or 24 weeks), and consequently little is known
about whether effects of training can be maintained or
even improved in the longer term. Secondly, the effects
of exercise on numerous physiologic outcomes, i.e., bone
metabolism, glucose tolerance, cardiac structure and
function and peripheral vascular function, have yet to be
described in PCa patients. Thirdly, information about
the safety, feasibility and efficacy of exercise
interventions for PCa patients with advanced stage disease
involving bone metastases is scarce, as only one previous
study has included this population . Finally it is not
known whether results demonstrated in previous
exercise studies can be reproduced in alternative and
nonclinical settings, e.g., organized team sports .
Therefore the purpose of the present study is to
investigate 1) the effects of 12 weeks of recreational soccer on
body composition, fitness, cardiac structure and function,
peripheral vascular function, blood pressure, physical
function parameters, postural balance, muscle strength,
glucose tolerance, insulin sensitivity, and markers of
inflammation and bone metabolism and 2) whether
potential physiological and patient-reported effects of the
12 week soccer training intervention can be maintained or
improved further with an additional 20 weeks training at a
reduced training volume. The primary study endpoint is
changes in LBM from baseline to 12 weeks.
This study is a two-armed RCT, with one group playing
soccer (intervention group) and a waiting-list control
group, who is offered participation in the intervention
after the 8 months study period. The study has been
approved by the Danish National Committee on
Biomedical Research Ethics for the Capital Region (registration
number H-3-2011-131) and written informed consent
will be obtained from all participants before any study
procedures are undertaken.
Blinding and masking of data
Blinding of patients and soccer instructors in this kind
of study is not possible. All data will be entered into a
secure web server immediately after collection and will
not be available to study personnel at subsequent tests.
At the termination of the study a statistician blinded to
treatment assignment will perform all analyses before
disclosing any study outcome data to the study
coordinator and researchers involved in the study.
We aim to include and randomize 80 men with
histologically confirmed advanced or locally advanced PCa
presenting at Copenhagen Prostate Cancer Center and
Dept. of Urology, Copenhagen University Hospital
Rigshospitalet, Denmark. Patients aged < 76 years who have
received ADT for at least 6 months will be invited to
attend meetings which will outline the purpose of the
study, and offer more detailed information about the
investigations involved and the soccer intervention.
Assessments will be performed at the following
tions: The Panum Institute Copenhagen (dual-energy
X-ray absorptiometry [DXA] scans), The August Krogh
Building at the Department of Nutrition, Exercise and
Sports (cardio respiratory fitness test, peripheral vascular
function tests, electrocardiogram), The National Research
Centre for the Working Environment (balance, jump,
chair stand and stair climbing tests) and Department of
Cardiology, Copenhagen University Hospital, Gentofte
Hospital, Denmark (echocardiography). All training
sessions will take place at The Department of Nutrition,
Exercise and Sports, University of Copenhagen.
WHO performance level > 1.
Osteoporosis (T-score < 2.5).
Activity limiting pain from bone metastasis.
After successful completion of all baseline assessments
participants are randomized 1:1 to the soccer intervention
or control group. The randomization process will be
conducted by a research consultant at The Copenhagen Trial
Unit who has no other involvement in the study. The
study flowchart is presented in Figure 1.
Participants in the intervention group will practice soccer
for 12 weeks two-three times weekly. An experienced
soccer instructor will be in charge of all training sessions.
During weeks 14 training will consist of two weekly
sessions of 15 min of warm-up exercises (running, dribbling,
Figure 1 CONSORT diagram.
passing, shooting, balance and muscle strength exercises)
followed by 2 15 min of 57 a-side games. In weeks 58
the duration of each session will increase to 3 15-min
games after the warm-up, and in weeks 912 there will be
three weekly training sessions of the same duration. After
12 weeks all assessments will be repeated. Participants in
the intervention group will then continue bi-weekly
supervised training for an additional 20 weeks at the end of
which all assessments will be repeated to allow for
additional analysis of long-term effects (Figure 2). Training
will take place on a natural grass pitch. In adverse weather
conditions (i.e., < 5C or heavy rain) training will be
performed indoors. Participants will be told to avoid hard
tackles and other actions that carry a risk of injury.
Participants in the control group will be encouraged to
maintain their baseline physical activity level. However,
for ethical reasons, this advice will not be enforced, since
increasing physical activity levels in general is considered
beneficial to health.
All assessments will take place at baseline, and after
12 weeks and 32 weeks. Measurement of body
composition, peripheral vascular function, glucose tolerance,
blood pressure, and blood markers will be performed in
the morning after an overnight fast. Subjects will be
instructed to avoid intake of medication, caffeine and
vitamins, and to abstain from tobacco use for 12 h prior
to the above mentioned tests and to avoid strenuous
physical activities 48 h prior to all examinations.
Primary study endpoint
The primary study endpoint is the change in LBM as
determined by whole body DXA-scan (iDXA, Lunar
Corporation, Madison, WI, USA) according to standard
Secondary study endpoints
Secondary outcomes include body composition, measures
of physical functioning, assessment of cardiovascular and
metabolic function, blood test values and patient-reported
Assessment of total body BMC and areal BMD as well
as android, gynoid and total body fat mass will be
derived from the whole body DXA scan. Visceral fat mass
will be evaluated using the iDXA CoreScan software
(Lunar Corporation, Madison, WI, USA). BMC and areal
BMD of the hips and lumbar spine will be derived from
separate DXA scans. Height will be measured by a
stadiometer, body weight will be measured with a digital
platform scale and body mass index will be calculated
(weight in kg/(height in m)2).
Waist- and hip circumference
Waist circumference will be measured around the
abdomen at the level of the belly button, and the hip
circumference will be measured at the widest part of the hips
and hip to waist ratio will be calculated .
Physical function tests
Maximal oxygen uptake
Two hours after consuming a normal breakfast
participants will conduct a submaximal walking test on a
treadmill and an incremental test to exhaustion on a
cycle ergometer. The submaximal test will consist of
4 min of walking on a treadmill at 4.5 km/h to
determine oxygen uptake, respiratory exchange ratio and
heart rate during an activity similar to that of daily
living. After 4 min of passive rest, the incremental cycle
test will start with 4 min cycling at 40 W, with a
selfchosen cadence in the range of 7090 rpm, after which
the load will increase by 20 W each min until volitional
exhaustion. Oxygen uptake, respiratory exchange ratio
(RER) and ventilation will be determined by pulmonary
gas exchange measurements (MasterScreen CPX, Viasys
Healthcare, St Paul, Minnesota, USA). The physiological
criteria for approval of the maximal oxygen uptake
(VO2max) test will be RER 1.05 and leveling off on the
VO2 curve with an increase of <1 ml O2/min/kg with an
increase in work load of 20 W . Heart rate will be
determined in 5 s intervals throughout the incremental
test by a Polar Team System chest belt (Polar Oy, Kempele,
Finland). VO2max and maximal heart rate (HRmax) will
be defined as the highest oxygen uptake and heart rate
values obtained over a 30 and 15 s period, respectively.
Figure 2 Duration and frequency of soccer training sessions during the study period.
Flamingo balance test
Postural balance will be assessed with a modified
singleleg flamingo balance test . Subjects are instructed to
stand on one foot on a 3 cm wide and 5 cm high metal
bar with their eyes open for one min. Subjects are
permitted to move their arms and non-standing leg to assist
balancing. The number of falls will be counted and used
as a measure of postural balance.
Assessment of postural sway
Subjects will be asked to stand on a force platform
(AMTI R6-1000, Watertown, MA, USA), arms crossed
over the chest, and instructed to look at a 10 cm2 circle
placed 2.5 meters away from the platform at a height of
1.65 m. Vertical ground reaction force (Fz),
anteriorposterior moment (Mx) and medio-lateral moment (My)
will be sampled using custom made Matlab (Mathworks)
acquisition software at 100 Hz (16 bit A/D conversion,
DT9804, Data translation, Marlboro, MA, USA). The
Fz-, Mx- and My-signals will be digitally low-pass
filtered with a 4th order zero-lag Butterworth filter (8 Hz
cutoff ) . Displacement of the center of pressure will
be calculated as (x,y) = (x0 + My/Fz, y0 + Mx/Fz), where
(x0,y0) is the geometrical center of the plate. Balance will
be tested in three positions: 1) bilateral (60 s): feet close
together with skin contact both at heels and bases of
hallux; 2) unilateral (15 s): base of hallux of the free foot
placed on medial malleolus of the standing leg; 3)
tandem stand (15 s): both feet on the force plate with base
of hallux of one foot placed next to medial malleolus of
the other foot. Bilateral standing is performed once,
unilateral and tandem standing are performed in triplicate
and the trials with the smallest sway area will be used
for further analysis. The data acquisition method has
been previously described in detail elsewhere .
Counter movement jump (CMJ)
On a force platform (AMTI R6-1000, Watertown, MA,
USA) subjects will perform standard CMJs with hands
placed on the hips. On the signal go the subject is
instructed to bend their knees and jump as high as they
can without moving their hands. The vertical force
signal (Fz) obtained during the jump will be used to
calculate the offset impulse, i.e., the area under the force-time
curve, which will then be converted to velocity by
dividing by body mass, and finally converted to jump height
based on the relationship between kinetic and potential
energy . Subjects will perform three jumps separated
by 30-s resting periods and the highest jump height (cm
above ground) will be used in subsequent analysis.
Using a chair fixed to the ground with a seat 45 cm
above the ground subjects will be instructed to sit in the
middle of the chair, back straight, arms crossed over
their chest, feet flat on the floor. A mechanical contact
in the seat is connected to a computer which
automatically counts the number of rises. Correct standing
technique will be demonstrated first slowly, then quickly.
Subjects will be allowed to practice for two-three
repetitions before the start of the test. On the signal go the
subject will be asked to stand, then return to the seated
position, as many times as possible in 30 s .
Subjects will be instructed to climb up one flight of a
staircase (9 steps, 0.175 m each) as fast as they safely
can, taking one stair at a time, without holding the
handrails . The time taken by the subject between
touching the first step to reaching the last step will be
measured manually with a stopwatch.
Dynamic concentric muscle strength for the knee
extensors will be assessed with the one repetition maximum
(1RM) test measured in 2.5 kg intervals. After a
standardized warm-up the test load will start at 15 kg and
resistance will gradually be increased until failure. The
rest period between each attempt is 30 seconds. The
maximum weight lifted through a full range of motion
will be recorded as 1 RM .
Cardiovascular and metabolic function
Comprehensive transthoracic echocardiography will be
performed on a GE Vivid 9 ultrasound machine with a
2.5 MHz transducer (GE Healthcare, Horton, Norway).
The examination will be performed with the subjects
resting in lateral supine position in a dark room by two
experienced echocardiographers blinded for group
allocation. All examinations will be analyzed off-line in
random order, using the Echo Pac software version BT 11.0
by an independent and blinded echocardiographer. The
full echocardiographic protocol has been described
elsewhere . Cardiac structure will be evaluated from
parasternal long axis 2-D recordings at the mid-ventricular
level with measurement of left ventricular (LV)
enddiastolic diameter (LVEDD), interventricular septal wall
thickness (IVST) and posterior wall thickness (PWT). LV
mass is calculated from the formula 0.832 [1.05 [(LVID +
IVST + PWT)3] (LVID)3] and indexed according to body
surface area and LV volumes. LV ejection fraction will be
evaluated with Simpsons biplane method.
Right ventricular function will be evaluated as
tricuspid annular plane systolic excursion. Diastolic function
will be measured as peak transmitral inflow velocity in
early (E) and late (A) diastole and the corresponding
E/A-ratio and pulsed analyses of tissue Doppler Imaging
(TDI) of diastolic velocities E and A will be obtained
with a 5-mm pulsed (TDI) sample volume placed in the
lateral, septal, anterior and inferior plane of the mitral
annulus in the 2- and 4-chamber apical views. TDI peak
systolic velocity (S; cm/s) will also be measured. The
values of E will be reported as an average of the septal
and lateral early peak diastolic velocities and E/E will
be calculated as a measure of left ventricular filling
pressure. Two-D color tissue Doppler will be evaluated from
six basal segments of septal, lateral, anterior, inferior,
posterior, and anterior septal walls of the apical 2- and
4-chamber and long axis and values will be averaged.
Measurements will include S, E and A. Diastolic
dysfunction will be graded as previously described . LV
longitudinal systolic function will be evaluated by
2Dspeckle tracking analysis and longitudinal 2-D global
strain will be estimated using automated functional
imaging. LV longitudinal systolic shortening (LV
displacement) will be evaluated using tissue tracking as described
previously by others .
Peripheral vascular function
Measurements of the reactive hyperemic index (RHI)
and the augmentation index, respectively, will be
measured with peripheral arterial tonometry (PAT) under
standardized conditions in a quiet dark room. A
pneumatic probe will be placed on the tip of each index
finger and connected to a plethysmographic device
(EndoPat-2000, Itamar Medical Ltd, Caesarea, Israel).
After this PAT measurements will be made before and
during reactive hyperemia as previously described 
in order to derive RHI, a measure of microvascular
endothelial function, and the augmentation index, a
measure of arterial stiffness, normalized to a heart rate
of 75 bpm, respectively.
Oral glucose tolerance test (OGTT)
The participants will be asked to drink 0.5 L of a 15%
glucose solution within a 5-min period. Blood samples
will be collected prior to the 75 g glucose intake as well
as after 15, 30, 60, and 120 min to measure plasma
glucose and insulin. Glucose tolerance will be measured by
the 2 hour value and the area under the curve for
glucose. To determine whole body insulin sensitivity the
insulin sensitivity index (ISI) proposed by Matsuda and
Defronzo will be calculated from fasting and mean
plasma glucose and insulin concentrations obtained
from the measuring time points during the OGTT .
After a 1 hr resting period during the OGTT, blood
pressure will be measured with a digital
sphygmomanometer (OMRON-M7) 5 times on the left arm at 2 min
intervals. The average of the 5 measurements will be
recorded for subsequent analysis.
Blood sampling and analyses
Blood samples will be obtained from a cubital vein and
serve as a screening tool at baseline. Thus, hemoglobin
and iron status will be measured to avoid inclusion of
patients with anemia (Sysmex XE-2100, Sysmex America,
Inc., Lincolnshire, IL, USA). Coagulation markers of
International Normalized Ratio, activated partial
thromboplastin time (APTT) and trombocytes will be measured to
rule out coagulopathy (ILS ACL TOP, Instrumentation
Laboratory, 1930 Zaventem, Belgium and Sysmex XE-2100,
Sysmex America, Inc., Lincolnshire, IL, USA). Serum
concentrations of creatinine will be measured to rule out
kidney disorders and levels of aminotransferases, alkaline
phosphatase and bilirubine to rule out liver disorders
(MODULAR analyzers, Roche Diagnostics, Mannheim,
Germany). In addition all blood samples will be analyzed
at baseline, 12 and 32 weeks for total cholesterol,
lowdensity lipoprotein cholesterol, high-density lipoprotein
cholesterol, triglycerides, and glycosylated hemoglobin,
respectively, by automated analyzers (Cobas Fara, Roche,
Neuilly sur Seine, France) using enzymatic kits (Roche
Diagnostics, Mannheim, Germany, and Tosoh G7, Tosoh
Europe, Tessenderlo, Belgium). All of the above
mentioned blood markers will be analyzed in the Department
of Clinical Biochemistry at Copenhagen University
Hospital Rigshospitalet, Denmark.
All samples will also be analyzed for bone markers,
including procollagen type I C propeptide, osteocalcin,
Cterminal telopeptide, tartrate-resistant acid phosphatase
5b and leptin, using ELISA and AlphaLISA apparatus
(PerkinElmer, Cambridge, United Kingdom) at the
Scientific Laboratory at the University of Exeter, United
Information on socio-demographic and lifestyle
characteristics will be collected at baseline . Health-related
quality of life outcomes will be measured using the eight
sub scales of the Medical Outcomes Study Short Form
 and the 15 subscales of the European Organization
for Research and Treatment of Cancer (EORTC
QLQC30) . Diagnosis-specific symptoms and side-effects
will be measured with the supplement EORTC
QLQPR25. Anxiety and Depression will be measured with the
two subscales of the Hospital Anxiety and Depression
Scale [36,37]. Social support and network will be
measured with The Multidimensional Scale of Perceived
Social Support . Leisure time physical activity level will
be examined using a self-administrated questionnaire
classifying patients in the following groups: I) sedentary;
II) walking or cycling for pleasure; III) regular physical
exercise at least 3 hrs per week; or IV) intense physical
activity more than 4 hours per week. The Physical
Activity Scale will be used to assess average weekly physical
activity of sleep, work, and leisure time .
a standard deviation (SD) of 1.0 kg, 34 patients are
needed in each group with a significance level
(twosided) of 5% and a power of 80%. Due to possible
dropouts we plan to include 40 patients in each group.
Medical history and status
Detailed information about the time of PCa diagnosis,
disease stage, PSA level at the time of diagnosis,
duration of ADT at baseline, previous radiation treatment
or surgery and pre-existing comorbidities will be
obtained from the participants medical records.
GPS monitors (GPSport, Melbourne, Australia) will be
worn by participants in week 2 and 11 to record
standing, walking and running times, as well as running
speeds and distance covered.
In week 2 and 11 of the intervention participants
perceived exertion and experience of flow will be
determined with Visual Analogue Scales .
Serious adverse events occurring during the training will
be reported immediately to the Unit for Patient Safety in
the Capital Region of Denmark. Minor events related to
physical contact or stumbling can occur during training,
and only pain and soreness persisting for more than
24 h will be recorded.
Sample size calculations
Since recreational soccer has not previously been applied
as a rehabilitation strategy for men with PCa, the
possible effect size on LBM is unknown. However, Krustrup
et al.  have shown that the effect of soccer training
on LBM is comparable to that of progressive resistance
exercise . In men with PCa undergoing ADT
progressive resistance exercise has yielded increases in LBM
of 0.7 kg after 12 weeks of training . To detect a
0.7 kg difference in LBM between the groups, assuming
Data entry will be undertaken using a secure web
server and statistical analysis will be performed using
Statistical Analysis Systems (SAS) version 9.2. The
statistician will prepare results with no knowledge of
the randomization coding. The primary endpoint will
be reported as a two-sample t-test comparing change
scores in the two randomization groups. Significance
level will be set at 0.05.
Regarding secondary outcomes, the continuous
variables, i.e., VO2max, HRmax, waist and hip
circumferences, CMJ, and stair climbing parametres, and the
patient reported outcomes, respectively, will be reported
as either means with corresponding 95% confidence
limits or as medians and interquartile range (IQR). For
count data, i.e., the Flamingo balance test and the
sit-tostand test, Poisson regression will be used, and
categorical data, i.e., single questionnaire items, will be reported
as proportions and compared across randomization
groups using chi-squared tests or logistic regression.
Adverse treatment side-effects of ADT for PCa patients
include loss of LBM, increased fat percentage and
increased risk of myocardial infarction , fractures 
and diabetes , as well as reduced QoL .
Interventions aimed at mitigating these side effects are both
warranted and important for patient well-being .
The current study will provide a comprehensive
investigation into the effects of a relatively brief (12 weeks)
and medium-term (32 weeks) exposure to physical
exercise on numerous physiological outcomes including
body composition, cardiovascular function, bone health,
insulin sensitivity, mobility, muscle strength, balance and
patient reported outcomes such as QoL in PCa patients
undergoing ADT. Recreational soccer will be used as a
unique and novel rehabilitation initiative and, to the best
of our knowledge, this is the first time soccer has been
proposed as a complementary intervention in the
treatment of cancer. This is also the first study to examine
cardiac function in PCa patients with comprehensive
echocardiography, and to monitor the impact of exercise
training in PCa patients on cardiac function and
peripheral vascular function. Animal studies have provided
evidence that exercise training may counteract left
ventricular dysfunction associated with ADT in rodents
. Our study is therefore likely to provide important
and novel information about cardiovascular health in
PCa patients undergoing ADT.
The choice of soccer as an intervention is based on a
number of considerations. Firstly, participation in sport
is increasingly recognized as important for public health
 and recent evidence from a large prospective cohort
study shows that participation in organized sport is
associated with reduced mortality (hazard ratio = 0.71; 95%
CI = 0.56, 0.91) . Secondly, soccer is considered the
most prominent team sport in the world, with more
than 270 million active sports club players  and most
Danish men have played the game. Thirdly, recent
studies have shown that recreational soccer induces
beneficial musculoskeletal, metabolic and cardiovascular
adaptations in healthy untrained young men ,
middle-aged men with hypertension [50,51],
premenopausal women  and middle-aged men with type 2
diabetes . The positive effects obtained after 12
14 weeks of soccer training in the studies with healthy
untrained young men and premenopausal women were
maintained with a reduced training volume beyond a
one-year period following the intervention [53,54]. Mean
heart rates of 80-85% of HRmax and numerous (>190/h)
high intensity actions, i.e. dribbles, shots, turns, jumps,
sprints, accelerations, decelerations and tackles, may
explain why soccer effectively stimulates both aerobic and
anaerobic energy delivery systems [55,56]. In relation to
bone health, a topic of particular concern in the PCa
population, studies have found that 1214 weeks of
soccer training significantly increases lower extremity bone
mass  and volumetric BMD in the tibia  and
results in marked increases in plasma levels of osteocalcin
. Intense and diverse movements resulting in the
generation of large ground reaction forces are
hypothesized to account for these adaptations, as they represent
near optimal osteogenic stimuli . Further evidence of
the favourable musculoskeletal potential of soccer
movements comes from demonstration that the activity
pattern and high intensity actions involved in soccer
training provide marked increases in lower extremity
[49,54] as well as upper body LBM , and that the
whole-body muscle hypertrophic effects of soccer are
greater than for continuous running and interval
running, and as effective in increasing LBM as resistance
exercise . With regards to the cardio respiratory
fitness effects of soccer, it has been shown that short-term
soccer training was greater [60,61] or equal to 
training volume-matched continuous running programs, and
similar to the effects of high-intensity interval running
. Interestingly, soccer training was perceived as less
exhausting than both continuous and intermittent
running in young healthy men . Recreational soccer
therefore may constitute a highly motivating
exercisebased rehabilitation intervention. Importantly, soccer
training also provides peer-based psychosocial support
and added individual social capital , which is likely
to contribute to long-term adherence to training. Of
note, the above-mentioned studies investigated men and
women aged 1855 years. Less information is available
about the effects of soccer training for elderly (>65 years)
subjects but recent studies have shown that heart rate is
also high for elderly soccer players during small-sided
games  and cross-sectional studies have provided
evidence of elderly soccer players impressive
cardiovascular and musculoskeletal health profiles, with rapid
muscle force and postural balance scores equal to those
of 30 years-old untrained men .
One particular aim of this study is to address whether
an out-door intervention with little need for equipment
can achieve effect sizes comparable to those of
multimodal interventions requiring relatively expensive
training facilities, i.e. resistance exercise machines and
stationary bicycles. With a low cost to benefit ratio,
potential positive results from the study may be
disseminated to a broader population of men with PCa, in
cooperation with existing community-based soccer clubs.
This could potentially make an important contribution
to the cancer care pathway for PCa patients and make a
significant, positive impact on PCa survivorship both
short- and long term.
Finally, a goal of the current research project is to
build a bridge between the clinical environment and the
existing expertise within exercise- and sports psychology
and physiology in order to meet the legitimate demands
from male cancer survivors for patient-centered and
action-orientated interventions aimed at improved health
. Collaboration between health care specialties, i.e.,
oncology, urology, cardiology, psychology, physiotherapy
and exercise physiology in the current study is crucial for
its success and the results are likely to benefit the care and
rehabilitation of PCa patients with possible favorable
effects on long-term clinical outcomes.
ADT: Androgen deprivation therapy; BMC: Bone mineral content; BMD: Bone
mineral density; DXA: Dual-energy X-ray absorptiometry; IVST: Interventricular
septal wall thickness; LBM: Lean body mass; LV: Left ventricular; LVEDD: Left
ventricular end-diastolic diameter; LVID: Left ventricular internal dimension;
OGTT: Oral glucose tolerance test; PAT: Peripheral arterial tonometry;
PCa: Prostate Cancer; PWT: Posterior wall thickness; QoL: Quality of life;
RER: Respiratory exchange ratio; RHI: Reactive hyperemic index;
RM: Repetition maximum; TDI: Tissue doppler Imaging; VO2max: Maximal
JM and JFC developed the study concept and initiated the project together
with MR and PK. KB, JFS, LJA, PRH, TH, LLA, EWH, KBC and JU assisted in
further development of the protocol. JU drafted the manuscript. KB will
provide access to patients. All authors contributed to and approved the final
The study is supported by grants from The Center for Integrated
Rehabilitation of Cancer patients (CIRE), a center established and supported
by The Danish Cancer Society and The Novo Nordisk Foundation. The
project is also supported by TrygFonden, Preben & Anna Simonsen Fonden
and The Beckett Foundation.
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