EURURO Vol. 72 No. 2

294 320

1. Introduction
Androgen deprivation therapy (ADT) is extensively used in
the management of prostate cancer (PCa) but is associated
with an array of adverse effects One adverse effect
which has a considerable impact on quality of life is fatigue
and a substantial proportion of men with PCa suffer from
fatigue, with 40% or more of those on long-term ADT
reporting chronic fatigue or clinically-relevant fatigue
which interferes with daily functioning .
Exercise interventions have shown positive effects on
reducing or mitigating fatigue As a result, recent expert
reviews in urology/oncology have incorporated aerobic and
resistance exercise interventions as evidence-based strategies
to mitigate toxicities from ADT including fatigue . We
and others have reported in relatively short-term
trials (< 6 mo) of progressive resistance (strength) training
and/or aerobic exercise consisting of walking/jogging or
cycling at moderate to high intensity can reduce or prevent
the worsening of fatigue, as can the same exercise modes
when combined with dietary advice/behavioural components
in a lifestyle intervention . However, these studies have
examined only the effects of short-term interventions with
longer-term outcomes rarely reported. Importantly, advance-
ments to exercise protocols/prescription are required to
understand the potential of different exercise modalities on
fatigue. Accordingly, we report for the first time the efficacy of
a 1-y long randomised controlled trial (RCT) of varying
exercise interventions in PCa patients undergoing ADT with
changes in fatigue and vitality assessed over 6 mo and 12 mo.
2. Patients and methods
2.1. Patients
Two-hundred and ninety-three patients with PCa were screened for
participation from 2009 to September 2012 at Perth, Western Australia
and Brisbane, Queensland and their progress through the study is
detailed in . Inclusion criteria included histologically documented
PCa, minimum exposure to ADT of 2 mo, without prostate-specific
antigen (PSA) evidence of disease activity, and anticipated to receive ADT
for the subsequent 12 mo. Exclusion criteria included bone metastatic
disease, musculoskeletal, cardiovascular, or neurological conditions that
could inhibit them from exercising, inability to walk 400 m or undertake
exercise, and structured resistance and aerobic training in the previous
3 mo. All participants obtained medical clearance from their physician.
The study was approved by the University Human Research Ethics
Committee and all participants provided written informed consent.
2.2. Study design and random assignment
This was a three-armed RCT. Primary endpoints were bone mineral
density and cardiovascular capacity , which will be reported
elsewhere, with secondary endpoints including physical function and
self-reported patient outcomes. Potential participants were primarily
identified by their treating urologist/oncologist and referred to the study
coordinator to confirm eligibility, describe the study, and obtain informed
consent. Study patients underwent a familiarisation session that included
correct exercise technique followed by baseline testing comprising
physical tests, questionnaires, and a venous blood sample. Following
baseline assessment, participants were stratified according to time on
ADT (< 6 mo or 6 mo) and randomly allocated to: impact
loading + resistance training (ILRT), aerobic + resistance training (ART),
or to usual care/delayed exercise (DEL) by computer random assignment.
2.3. Exercise training program
ILRT was undertaken twice weekly in University-affiliated exercise
clinics for 12 mo. Sessions were supervised with up to 10 participants.
The impact-loading component consisted of a series of bounding,
skipping, drop jumping, hopping, and leaping activities that produced
ground reaction forces of 3.4–5.2 times body weight, and was
progressive in nature. Specific details on progression are described
elsewhere . Resistance training consisted of six principal exercises
that targeted the major upper and lower body muscle groups: chest
press, seated row, shoulder press, leg press, leg extension, and leg curl,
with supplementary exercises. Patients performed two to four sets of
each exercise at an intensity of 6–12 RM (maximal weight that can be
lifted 6–12 times). In addition, the ILRT group undertook home training
twice weekly that consisted of two to four rotations of skipping/hopping/
leaping/drop jumping . ART underwent supervised exercise in the
clinic twice weekly for the initial 6 mo. The aerobic-based component
consisted of 20–30 min of exercise at 60–75% of estimated maximal
heart rate using various modes which included walking/jogging and
cycling or rowing on stationary ergometers. Resistance exercise during
the initial 6 mo was the same as that undertaken in the ILRT regimen. In
addition, participants were encouraged to undertake home-based
aerobic activity such as walking or cycling with the goal to accumulate
150 min/wk of aerobic activity. For the 2nd 6 mo, patients were provided
with a home-based maintenance program similar to our previous report
. DEL were provided with a printed booklet with information about
exercise for the initial 6mo, followed by 6mo of twice weekly supervised
exercise on a cycle ergometer at an intensity of 70% maximal heart rate
and flexibility exercises in the clinic. During the 12-mo study period,
ILRT, ART, and DEL were asked to maintain customary physical activity
and dietary patterns.
2.4. Fatigue and vitality
Study endpoints of fatigue and vitality were assessed at baseline, 6 mo,
and 12 mo. Fatigue was assessed using the European Organisation for
Research and Treatment of Cancer Quality of Life Questionnaire Core 30
(EORTC QLQ-C30; . Fatigue is a three-item symptom subscale
with higher scores representing greater fatigue Vitality (energy
level and fatigue) was assessed with the Short Form-36 Health Survey
(SF-36; ) . The Vitality scale of the SF-36 is a four-item
subdomain measure with scores ranging from 0 to 100, with higher
values indicting more vitality .
Patient summary: We compared the effects of different exercise modes on fatigue in men
on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced
vitality. We conclude that undertaking some form of exercise will help reduce fatigue,
especially in those who are the most fatigued.
# 2017 European Association of Urology. Published by Elsevier B.V. This is an open access
article under the CC BY-NC-ND license ).
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