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Can exercise ameliorate treatment toxicity during the initial phase of
testosterone deprivation in prostate cancer patients? Is this more effective than
BMC Cancer 2012, 12:432doi:10.1186/1471-2407-12-432
Robert U Newton (email@example.com)
Dennis R Taaffe (firstname.lastname@example.org)
Nigel Spry (email@example.com)
Prue Cormie (firstname.lastname@example.org)
Suzanne K Chambers (email@example.com)
Robert A Gardiner (firstname.lastname@example.org)
David HK Shum (email@example.com)
David Joseph (firstname.lastname@example.org)
Daniel A Galvão (email@example.com)
27 August 2012
20 September 2012
26 September 2012
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Can exercise ameliorate treatment toxicity during
the initial phase of testosterone deprivation in
prostate cancer patients? Is this more effective than
Robert U Newton1*
* Corresponding author
Dennis R Taaffe1,2,3
Suzanne K Chambers1,6
Robert A Gardiner1,7
David HK Shum6
Daniel A Galvão1
1 Edith Cowan University Health and Wellness Institute, Edith Cowan University,
270 Joondalup Drive, Joondalup, Western Australia 6027, Australia
2 School of Environmental and Life Sciences, The University of Newcastle,
Newcastle, NSW, Australia
3 School of Human Movement Studies, The University of Queensland, Brisbane,
4 Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands,
5 Faculty of Medicine, University of Western Australia, Nedlands, WA, Australia
6 Behavioural Basis of Health Program, Griffith Health Institute, Griffith
University, Brisbane, QLD, Australia
7 Centre for Clinical Research at Royal Brisbane Hospital, The University of
Queensland, Brisbane, QLD, Australia
There has been substantial increase in use of androgen deprivation therapy as adjuvant
management of prostate cancer. However, this leads to a range of musculoskeletal toxicities
including reduced bone mass and increased skeletal fractures compounded with rapid
metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and
negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity,
greater distress and reduced quality of life. Numerous research studies have demonstrated
certain exercise prescriptions to be effective at preventing or even reversing these treatment
toxicities. However, all interventions to date have been of rehabilitative intent being
implemented after a minimum of 3 months since initiation of androgen deprivation, by which
time considerable physical and psychological health problems have manifested. The pressing
question is whether it is more efficacious to commence exercise therapy at the same time as
initiating androgen deprivation, so treatment induced adverse effects can be immediately
attenuated or indeed prevented.
We are proposing a multi-site randomized controlled trial with partial crossover to examine
the effects of timing of exercise implementation (immediate or delayed) on preserving long-
term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors,
and supporting mental health in men receiving androgen deprivation therapy. 124 men who
are about to initiate androgen deprivation for prostate cancer will be randomized to
immediate or delayed groups. Immediate will commence a 6-month exercise program within
7–10 days of their first dose. Delayed will receive usual care for 6 months and then
commence the exercise program for 6 months (partial cross-over). Immediate will be free to
adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements
for primary and secondary endpoints will take place at baseline, 6 months and 12 months.
This project is unique as it explores a fundamental question of when exercise implementation
will be of most benefit and addresses both physical and psychological consequences of
androgen deprivation initiation. The final outcome may be adjunct treatment which will
reduce if not prevent the toxicities of androgen deprivation, ultimately resulting in reduced
morbidity and mortality for men with prostate cancer.
Prostate cancer, Androgen deprivation therapy, Exercise, Resistance training, Aerobic
There has been a substantial increase in the use of temporary androgen deprivation therapy
(ADT) as an adjuvant to radical radiation and surgical therapies for management of prostate
cancer[1,2] with substantial periods of ADT now routinely applied to improve outcomes at 5,
10 and 15 years post diagnosis[2-4]. More than 2,000 men in Australia and more than
80,000 in the USA commence on-going ADT for prostate cancer each year. However,
ADT leads to a range of well-established musculoskeletal toxicities including reduced bone
mass and increased skeletal fractures[7,8] compounded with rapid metabolic alterations
including increased body fat, loss of lean mass, insulin resistance and negative lipoprotein
profile[9-15]. Recent work, including our own current Australian cohort, suggests an
increased incidence of cardiovascular and metabolic morbidity associated with temporary
ADT[16-20] and we have also reported significantly increased distress and reduced
quality of life (QOL)[22,23]. Our team has shown that even a 9-month exposure to ADT
leads to significant reductions in bone mass across different clinical sites concurrently with
severe loss of lean mass and increased trunk and whole body fat mass, all surrogate indicators
of osteoporosis/skeletal fractures and cardiovascular/metabolic complications. Currently,
there is no established treatment to reverse bone loss and the array of metabolic adverse
effects associated with severe hypogonadism from temporary ADT. Preliminary clinical trials
by our team[24-26] and others[27,28] have suggested high efficacy of exercise for these
patients but evidence is limited to only a few studies with men on long-term androgen
deprivation[24,27-29]. We have shown that a combined program of resistance and aerobic
exercise leads to a number of significant and clinically meaningful benefits including reversal
of muscle loss in men receiving ADT for an average of approximately 14 months. A
critical but as yet unanswered research question is to determine whether it is more efficacious
to commence exercise therapy at the onset of androgen deprivation so treatment induced
adverse effects can immediately be attenuated or even completely prevented. This has not
been addressed in any exercise trials to date and has the potential to prevent much of the
ADT toxicities from the outset rather than try to rehabilitate the patient from the effects of
long-term ADT later. A recent report showed that physical function and quality of life are
compromised within 3 months of commencing ADT suggesting that up-front exercise
interventions are needed to counteract these losses, as well as the marked reductions in bone
density and bone strength. Importantly, it appears the initial beneficial effects of resistance
and aerobic exercise programs are similar for neuromuscular and physical function regardless
of whether patients are on acute (3–6 months) or chronic (>6 months) ADT. Such
preliminary evidence supports the hypothesis that exercise might be best initiated when ADT
commences, to enhance physical function, retain structure and improve the patient’s
acceptance of hormone therapy. This is an important finding as it suggests that exercise may
still benefit men during acute ADT, but no research has trialled this from time zero; that is
initiation of ADT. This is a considerable gap in our understanding of the management of
prostate cancer and ADT.
Having successfully completed several pilot studies, a randomised controlled trial (RCT) and
ongoing RCTs in prostate cancer[24-26,31-34], this trial will drill down to the specifics of
exercise as medicine to improve skeletal health, physical function, quality of life and mental
health implemented immediately when patients initiate ADT. We propose a RCT with partial
crossover to examine the effects of the timing of exercise implementation. We will evaluate
the following hypotheses:
1) It is more efficacious to commence exercise therapy at the onset rather than after six
months of ADT; and
2) ADT side effects, in particular the substantial initial bone loss, can be prevented by a 6-
month exercise program concurrently undertaken at the onset of ADT.
The primary endpoint will be spine and hip aBMD determined by DXA. Secondary endpoints
will include: 1) volumetric BMD (vBMD) and micro-architecture at the tibia, 2) body
composition (lean mass and fat mass/abdominal obesity), 3) blood pathology (glucose
metabolism, lipid profile, prostate specific antigen (PSA), testosterone, bone formation and
resorption markers), 4) physical function, muscle strength and balance, 5) physical activity
level and motivation, and 6) health-related quality of life and psychological distress.
The ultimate outcome will be guidelines for the prescription of exercise for the prevention of
ADT toxicities, primarily those related to long-term skeletal health and physical function.
This project is unique as it explores a fundamental question of when exercise implementation
will be of most benefit to men undertaking ADT. The final outcome may be an adjunct
treatment which will prevent major toxicities of ADT, ultimately resulting in reduced
morbidity and mortality for men with prostate cancer.
We are proposing a single-blinded (investigators and testing personnel blinded to group
allocation) RCT with partial crossover to examine the effects of the timing of exercise
implementation. An immediate exercise group (IE) will undertake the exercise program for 6
months. After 6 months, the delayed exercise group (DE) will be crossed to receive the same
intervention program (Table 1).
Table 1 Summary of the Intervention Arms
Immediate Exercise (1)
Delayed Exercise (2)
0 6 12
Exercise Intervention (n =62)
Usual Care (n = 62)
No formal intervention
Subjects will be recruited by invitation of their specialist (radiation oncologist/urologist) as
previously reported in completed and ongoing trials [24,26,32]. Those entering the study will
undertake a series of familiarisation sessions and baseline measurements prior to
randomisation (Figure 1).
Figure 1 CONSORT Diagram
Randomisation and stratification
Patients will be randomly allocated in a ratio of 1:1 to the two treatment arms for IE and DE
groups, subject to maintaining approximate balance regarding stratification for age (<=70
yr>) and smoking status (yes/no). A research methods consultant will be responsible for this
randomisation and confirming the groups are balanced on these parameters. The chief
investigators, exercise physiologists, psychologists and other researchers conducting the
study measures will be blinded to a given participant’s group allocation. The exercise
intervention will be provided by exercise physiologists not in the research team or performing
the tests (single blinded).
One hundred and twenty-four men (62 subjects per arm) beginning treatment for prostate
cancer involving ADT with no regular exercise (undertaking structured aerobic or resistance
training two or more times per week) within the past 3 months will be recruited by invitation
of their attending specialist in the Perth, Western Australia, and the Central Coast region of
New South Wales. All participants will be able to walk 400-m and will require physician
consent. Exclusion criteria will include prior exposure to ADT (e.g. those re-initiating ADT
from intermittent programs), existing hypogonadism, established metastatic bone disease,
established osteoporosis, those taking medications known to affect bone metabolism (e.g.
bisphosphonates), acute illness or any musculoskeletal, cardiovascular or neurological
disorder that could inhibit or put them at risk from exercising. The protocol has been
approved (ID: 7869 NEWTON) by the University Human Research Ethics Committee and all
subjects will provide written informed consent.
All measurements for primary and secondary endpoints will take place at baseline, 6 and 12
months. Additional blood measures, scans and questionnaires will also be undertaken at 3
months to track changes over time during the initial 6 months for bone formation and
resorption markers. Body composition measures for muscle and fat mass will also be
performed at 3-month intervals to track the trajectory of change in these outcomes.
Calcium and vitamin D
All participants will receive standard daily supplementation with calcium (1,000 mg/d) and
vitamin D3 (800 IU/d).
Primary study endpoints
BMD (g/cm2) of the hip (total hip) and lumbar spine (L2-4) as well as whole body bone
mineral content (BMC, g) will be assessed by DXA (Hologic Discovery A, Waltham, MA).
The Instant Vertebral Assessment (IVA) and Quantitative Morphometry (QM) program will
be used to determine the presence or absence of vertebral fractures prior to initiation of the
Secondary study endpoints
Volumetric BMD and bone architecture
Three dimensional pQCT (XCT3000, Stratec, Pforzheim, Germany) will be used to measure
volumetric BMD and micro-architecture at the tibia. This technique provides additional data
on trabecular and cortical density and geometry with actual prediction of fracture thresholds.
Methods for analysis will be as previously described.
In addition to BMD, regional and whole body lean mass (including appendicular skeletal
muscle mass) and fat mass will be derived from the whole body DXA scan. Measurement of
trunk adiposity is an important indicator of chronic disease risk, and will be assessed from
trunk fat mass obtained from the whole body scan and the ratios of trunk fat to limb fat, and
trunk fat to total fat. Images from the pQCT scans will also be analysed for muscle density
and cross-sectional area for the lower limbs.
Testosterone, prostate specific antigen (PSA), insulin, glucose, haemoglobin A1c (HbA1c),
C-reactive protein (CRP), bone formation [alkaline phosphatase, Pro collagen Type 1 N-
Terminal Pro peptide (PINP)] and resorption [C-terminal telopeptide of type I collagen
(CTX)] markers, vitamin D and lipid profile levels will be measured commercially by an
accredited Australian National Association of Testing Authorities (NATA) laboratory
(Pathwest Diagnostics, Perth, Western Australia).
Blood pressure and arterial stiffness
A validated oscillometric device (HEM-705CP, Omron Corporation, Japan) will be used to
record brachial BP at the dominant arm in triplicate. Central (ascending aortic) BP and
indices of arterial stiffness will be determined using a SphygmoCor system (AtCor Medical,
Sydney, Australia). Radial artery pressure waveforms will be captured at the right arm by
applanation tonometry using a high fidelity micromanometer (SPC-301, Millar Instruments,
Houston, Texas, USA). A generalised transfer function is applied to the radial artery
waveform in order to obtain the pressure waveform at the ascending aorta. This method has
been validated against invasive techniques for determination of central BP and the
augmentation index (AIx) is a marker of systemic arterial stiffness.
Muscle strength and balance
Prior to muscle testing, subjects will be familiarised with all assessment procedures. In
addition, a warm-up consisting of aerobic activity and stretching will be undertaken.
Dynamic concentric muscle strength for the leg press, chest press and seated row undertaken
in the program will be measured using the one repetition maximum (1-RM) method. The 1-
RM is the maximal weight an individual can move through a full range of motion without
change in body position other than that dictated by the specific exercise motion. A
Neurocom Smart Balancemaster (Neurocom, OR, USA) will be used to assess standing
balance. This device measures ground reaction force to track whole body centre of pressure
and a tilting visual field and support platform to separate the visual, somatosensory and
vestibular balance sense of the patient. Falls self-efficacy will be determined using the
Activities-Specific Balance Confidence scale. During the course of the intervention, all
participants will record any falls that take place and submit monthly fall records to the
Objective measures of physical function
A battery of tests will be used to assess functional performance[24,37]. Tests will be
performed in triplicate (except for the 400-m walk which will be performed once) with
sufficient recovery time between trials. The best performance on each test will be used in the
analyses. The tests will be; 1) repeated chair rise, 2) stair climb, 3) 6-m backward tandem
walk, 4) 6-m walk, usual and fast pace, and 5) 400-m walk. Performance in each test will be
timed electronically using a Kinematic Measurement System (Fitness Technology, Australia)
Physical activity level and motivation
Self-reported physical activity will be assessed by the leisure score index from the Godin
Leisure-Time Exercise Questionnaire. ActiGraph activity monitors (triaxial accelerometer,
GT3X+, Actigraph, Pensacola, Florida) will be used to objectively assess physical activity
levels and sedentary time over a 7-day period. A 6-item questionnaire will be used to
assess the domain-specific sedentary behaviour.
The Theory of Planned Behaviour (TPB) is the most widely utilised behavioural framework
when examining physical activity motivation in cancer survivors. Therefore, physical activity
motivation will be assessed in accordance with the TPB. TPB constructs (affective and
instrumental attitude, injunctive and descriptive norm, self-efficacy, perceived behavioural
control, intention, and planning) will be assessed in accordance with established guidelines
using standardised items.
Health-related quality of life and psychological distress
Health-related QOL will be measured using the Medical Outcomes Study Short-Form 36 (SF-
36), European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and
EORTC QLQ-PR25 as well as a health history questionnaire. This validated instrument is an
integrated system to assess QOL in cancer patients and has been extensively employed in
clinical trials. The Brief Symptom Inventory-18 (BSI-18) will be used to assess
psychological distress (Anxiety, Depression and Somatisation). Higher somatization and
anxiety as measured by the BSI-18 is associated with greater physical inactivity in cancer
survivors. The Impact of Events Scale (IES) and the Memorial Anxiety Scale for Prostate
Cancer (MAX-PC) will be used to measure cancer specific distress[41,42]. A core self-
evaluation questionnaire and lifestyle individual resilience scale will be used to assess core
self-evaluation and three related aspects of resilience (individual, social–peers and social–
family resources). Fatigue will be assessed using the Functional Assessment of Chronic
Illness Therapy-Fatigue (FACIT-F) questionnaire. The FACIT-F is a 13 item scale commonly
used to assess fatigue in cancer patients as well as cancer patients receiving exercise
interventions. Items from the Pittsburgh Sleep Quality Index (PSQI) will be used to
measure sleep quality. The PSQI is used to assess quality of sleep over a 1-month
interval, and has been shown to be reliable and sensitive to change.
The intervention program will comprise resistance, aerobic and impact-loading exercises
undertaken 3 times per week in an exercise clinic. The frequency of resistance and aerobic
exercises will alternate weekly so two aerobic/impact loading and one resistance/impact
loading sessions are performed in the first week and two resistance/impact loading and one
aerobic/impact loading are performed in the subsequent week. Resistance training sessions
will take approximately 60 minutes (this includes the warm-up and cool-down periods) and
will be conducted in the Exercise Clinics at Edith Cowan University (ECU) in Perth and
seven other partner sites in Western Australia: Perth; Mandurah; and Bunbury. We also have
another site at the University of Newcastle where we have identical equipment and
procedures. The programme will include exercises such as leg press, leg extension, leg curl,
chest press, seated row, lat pulldown and bicep curl that target the major upper and lower
body muscle groups, which we have used in a number of previous studies[24,26,37,47]
including men on ADT. To ensure the progressive nature of the training program, subjects
will be encouraged to work past the specific repetition maximums (RMs) prescribed. The
resistance will be increased by 5-10 % increment for the next set/training session if the
subject is able to perform more repetitions than the RMs specified during a set. Intensity will
be manipulated from 6-12-RM (e.g. the maximal weight that can be lifted 6 to 12 times)
using 1–4 sets per exercise. The aerobic component will include 25–40 minutes of
cardiovascular exercise using various modes such as walking or jogging on a treadmill,
cycling or rowing a stationary ergometer, or exercising on a cross training machine. Target
intensity will be 60-85 % estimated maximum heart (220 – age) with individual heart rate
watches (Polar Electra Oy, Finland) provided for each participant. In addition to the clinic
training, participants will be encouraged to undertake twice weekly home-based training
incorporating aerobic activity (e.g. walking, cycling) and a modified version of the impact-
loading regimen (only including hopping, leaping and drop jumping) for the duration of the
study. The impact-loading regimen will be performed a minimum of 3 times per week for the
duration of the trial, in combination with the resistance and aerobic exercise. For the first 10
weeks, 2 rotations will be performed of skipping (30 sec), bounding over soft hurdles (13–16
cm), and drop jumping (10–15 cm). In the second 10-week period, hopping on one leg (10
times) will be added, leaping (10 times) will replace skipping, and 4 rotations of bounding
(19–25 cm), drop jumping (20–25 cm), hopping, and leaping will be performed for the
remainder of the programme. These activities result in substantial peak ground reaction
forces ranging from 3.4 to 5.2 times body weight providing excellent stimulus to bone yet
proven safe and accepted by older people.
All exercise sessions will be conducted in small groups of up to 6–10, with participants
exercising in pairs and under direct supervision to ensure correct technique and minimize the
risk for injury. Each session will commence with a 10-minute warm-up comprising low-level
aerobic activities such as walking and stationary cycling, as well as stretching and conclude
with a 5-minute cool-down period of stretching activities. In order to reduce the possibility of
boredom and overreaching the exercise program will be periodised by cycling emphasis on
intensity and volume. Also, within sessions variations of circuit training and intermittent
exercise sessions (intervals of high and low intensity exercise) will be introduced. The
exercise program will be designed to provide optimal stimulus to the skeletal,
cardiorespiratory and neuromuscular systems while maximizing compliance and retention.
All participants will be asked to maintain customary physical activity and dietary patterns
over the intervention period (apart from the programmed exercise). Physical activity and
dietary intake will be assessed at baseline, 6 and 12 months. During the course of the study,
participants will be required to maintain an activity log and record their recreational physical
activities. Participants in the DE group will be contacted every 4 weeks to encourage them to
maintain current physical activity levels and record their activities. Dietary intake, at the
same time points as for physical activity, will be assessed using a 4-day dietary record.
Dietary information will be derived using the FoodWorks software program.
Calculation of sample size
Data from our 36-week study in prostate cancer survivors initiating ADT indicates that
the standard deviation (SD) for change in our primary outcome of BMD equates to
approximately 4.5 % and 3.3 %, for the hip and lumbar spine, respectively. With ADT, the
annual loss is reported to be 2-8 % at the spine and 1.8-6.5 % at the hip [49,50] and based on
our 36-week data, we obtained an initial loss of 1.5 % and 3.9 % for the hip and lumbar
spine, respectively. Therefore, we anticipate losses of approximately 1.5 % and 3.5 % at the
clinically relevant fracture sites of the hip and spine. We anticipate a difference between the
immediate and delayed exercise groups of approximately 2.5 % at the hip and 4.5 % at the
lumbar spine, which would be clinically significant and substantially reduce the risk for
fracture. A priori, 51 subjects per group will be required to achieve 80 % power at an alpha
level of 0.05 (two-tailed), and to demonstrate a difference between groups at each bone site at
the end of the 6-month intervention. Previous experience in our exercise trials indicates an
attrition rate of up to 20 % over the course of the study period. Therefore, to adequately
ensure that we have sufficient subject numbers at the end of the intervention, 124 subjects
will be randomised in a ratio of 1:1 to the immediate and delayed exercise groups,
respectively. A sample size of 124 will also provide us with sufficient power to detect
differences in our secondary outcomes which all have larger effect sizes based on our
Data will be analysed using SPSS statistical software package and an intention-to-treat
approach will be applied. Analyses will include standard descriptive statistics, Student’s t
tests, correlation and regression, and two-way (group x time) repeated measures ANOVA (or
ANCOVA as appropriate) to examine differences between groups over time. All tests will be
two-tailed and an alpha level of 0.05 will be applied as the criterion for statistical
This is the first intervention using a combination of resistance, aerobic and impact loading
exercise implemented immediately with initiation of ADT as opposed to long-term androgen
deprivation. The principal outcome of this project will be the determination of whether it is
more efficacious to commence exercise therapy at the onset of ADT so treatment induced
adverse effects can be immediately attenuated or even completely prevented. This is an
exciting possibility. Second, this is the first study to our knowledge using pQCT to assess
bone outcomes of a therapeutic exercise intervention in a cancer population. Importantly, this
simple and cost effective intervention strategy may provide comparable benefits to
pharmaceutical interventions (e.g. bisphosphonates) without exposing patients to additional
potential side effects[36,51,52] or the high financial cost of these drugs. The most important
outcome will be clinical guidelines for the concurrent prescription of exercise for the
management of men initiating ADT to preserve long-term skeletal health, reduce metabolic
and cardiovascular morbidities, maintain physical function and alleviate psychological
distress and depression associated with severe hypogonadism resulting from temporary ADT.
By examining psychological outcomes of depression and distress we are addressing all
aspects of ADT toxicities in the initiation phase, an important time when patient discomfort is
greatest but unfortunately not addressed to date. This holistic approach to ADT toxicity will
result in more effective clinical guidelines for managing patients, in particular maximizing
uptake and long term adherence of exercise therapy. In terms of advancement of prostate
cancer care, we expect dissemination of the knowledge gained from this project to reduce
fracture risk, improve physical and functional ability, quality of life, mental health and
ultimately survival rates in this population. In particular, we hope to establish that exercise
implemented as men initiate ADT can offer an array of positive patient outcomes and this
strategy is far superior to the current delayed rehabilitation approach. Such benefits, apart
from enhancing quality of life, could significantly reduce health care costs and ultimately
ADT, Androgen deprivation therapy; QOL, Quality of Life; RCT, Randomized Controlled
Trial; IE, Immediate Exercise Group; DE, Delayed Exercise Group; PSA, Prostate Specific
Antigen; DXA, Dual Energy X-ray Absorptiometry; ABMD, Areal Bone Mineral Density;
pQCT, Quantitative Computed Tomography; vBMD, Volumetric Bone Mineral Density;
IVA, Instant Vertebral Assessment (IVA); QM, Quantitative Morphometry (QM); Hba1c,
Hemoglobin A1c; CRP, C- reactive protein; PINP, Pro Collagen Type 1 N-Terminal Pro
Peptide; CTX, C-terminal Telopeptide of Type I Collagen; 1-RM, One Repetition Maximum;
IES, Impact of Events Scale; MAX-PC, Memorial Anxiety Scale for Prostate Cancer; SF-36,
Medical Outcomes Study Short-Form 36; EORTC, European Organisation for Research and
Treatment of Cancer; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue;
TPB, Theory of Planned Behaviour; BSI-18, The Brief Symptom Inventory-18; LL-FI, The
Late Life - Function Index; PSQI, Pittsburgh Sleep Quality Index
The author(s) declare that they have no competing interests.
RUN, DRT, NS and DAG developed the study concept and protocols and initiated the
project. DJ, RAG, DHKS, PC and SKC assisted in further development of the protocol. RUN,
DRT, NS, PC and DAG drafted the manuscript. NS, DJ, SKC, DHKS and RAG will provide
access to patients. RUN, DRT, PC and DAG will implement the protocol and oversee
collection of the data. All authors contributed to and approved the final manuscript.
This project has been funded by Cancer Australia, Prostate Cancer Foundation of Australia
and Beyond Blue (NHMRC# 1029901). DAG is funded by a Movember New Directions
Development Award obtained through Prostate Cancer Foundation of Australia’s Research
Program. PC is supported by the Cancer Council Western Australia Postdoctoral Research
Fellowship. SKC is supported by an Australian National Health and Medical Research
Council Fellowship (ID 496003).
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