prehabilitation for adults diagnosed with cancer: a systematic...
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Eur J Cancer Care. 2019;e13023. wileyonlinelibrary.com/journal/ecc | 1 of 22https://doi.org/10.1111/ecc.13023
© 2019 Crown copyright. European Journal of Cancer Care © 2019 John Wiley & Sons Ltd
1 | INTRODUC TION
Prehabilitation offers a route to improving patient's physical status and buffering treatment‐related deconditioning between the time of cancer diagnosis and post‐treatment recovery. Prehabilitation
includes physical and psychological assessments that establish base‐line functioning and identify impairments that can impact on cancer treatment‐related morbidity, as well as providing targeted interven‐tions to maximise patient function prior to treatment onset (Silver & Baima, 2013). The primary goal of prehabilitation is “to prevent
Received:21November2017 | Revised:21September2018 | Accepted:17January2019DOI: 10.1111/ecc.13023
F E A T U R E A N D R E V I E W P A P E R
Prehabilitation for adults diagnosed with cancer: A systematic review of long‐term physical function, nutrition and patient‐reported outcomes
Sara Faithfull1 | Lauren Turner2 | Karen Poole1 | Mark Joy1 | Ralph Manders3 | Jennifer Weprin4 | Kerri Winters‐Stone4 | John Saxton5
1School of Health Sciences, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK2Frimley Health NHS Foundation Trust, Frimley, Surrey, UK3Exercise Physiology and Sports Science, University Surrey, Guildford, UK4School of Nursing, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon5Department of Sport Exercise and Rehabilitation, Northumbria University, Newcastle Upon Tyne, UK
CorrespondenceSara Faithfull, School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.Email: [email protected]
AbstractObjective: Prehabilitation is increasingly being used to mitigate treatment‐related complicationsandenhancerecovery.Anindividual'sstateofhealthatdiagnosis,in‐cluding obesity, physical fitness and comorbidities, are influencing factors for the occurrence of adverse effects. This review explores whether prehabilitation works in improving health outcomes at or beyond the initial 30 days post‐treatment and con‐siders the utility of prehabilitation before cancer treatment.Methods: Adatabasesearchwasconductedforarticlespublishedwithprehabilita‐tion as a pre‐cancer treatment intervention between 2009 and 2017. Studies with no 30 days post‐treatment data were excluded. Outcomes post‐prehabilitation were ex‐tracted for physical function, nutrition and patient‐reported outcomes.Results: Sixteen randomised controlled trials with a combined 2017 participants and six observationalstudieswith289participantswereincluded.Prehabilitationinterventionsprovided multi‐modality components including exercise, nutrition and psychoeducational aspects. Prehabilitation improved gait, cardiopulmonary function, urinary continence, lung function and mood 30 days post‐treatment but was not consistent across studies.Conclusion: When combined with rehabilitation, greater benefits were seen in 30‐day gait and physical functioning compared to prehabilitation alone. Large‐scale ran‐domised studies are required to translate what is already known from feasibility studies to improve overall health and increase long‐term cancer patient outcomes.
K E Y W O R D S
cancer, exercise, nutrition, prehabilitation, rehabilitation, survivorship
This article is published with the permission of the Controller of HMSO and the Queen’s Printer for Scotland.
2 of 22 | FAITHFULL eT AL.
or reduce the severity of anticipated treatment‐related impairments that may cause significant disability (page2)” (Silver & Baima, 2013). There are several systematic reviews of prehabilitation for those receiving cancer surgery (Boereboom, Doleman, Lund, & Williams, 2016; Carli et al., 2017; Singh, Netwon, Galvao, Spry, & Baker, 2013), and all suggest that prehabilitation enhances early discharge from hospital and reduces surgical adverse effects. There is a growing re‐quirement to include prehabil itation as part of the cancer pathway with three recent reports advising the value of prehabilitation, two intheUSA(NationalAcademiesofSciences,2018;Stoutetal.,2016)andoneintheUK(MacmillanCancerSupport,2018).However,ev‐idence that prehabilitation translates into better long‐term patient outcomes beyond the initial 30 days post‐treatment complications is lacking.
Challenges to providing prehabilitation are that cancer patients are highly likely to have comorbidities that complicate treatment deliveryandreducephysicalfitness(Sarfati,Koczwara,&Jackson,2016; Stairmand et al., 2015). Comorbid conditions associated with ageing and particularly excess body weight are common in patients presenting with cancer (Goodwin & Chlebowski, 2016), and evi‐dence from epidemiological studies suggests that comorbidities and poorer health are correlates of poorer survival (Land, Dalton, Jensen,&Ewertz2012a,2012b).There iscompellingevidenceforthe link between obesity and cancer outcomes (Calle, Rodriguez, Walker‐Thurmond, & Thun, 2003) with particular associations in thefollowingtumoursites;breast(Jiralerspong&Goodwin,2016),gastrointestinal (Brown & Meyerhardt, 2016), endometrial (Onstad, Schmandt, & Lu, 2016), prostate (Vidal et al., 2014) and haematologi‐cal cancers, including multiple myeloma and leukaemia (Yang, Drake, & Colditz, 2016). Obesity is an important risk factor for cardiovas‐cular, kidney disease, diabetes and some musculoskeletal disorders (2016). These obesity‐related comorbidities contribute to the ad‐verseeffectsofcancer treatment (Bradley,Dahman,Fau‐Anscher,&Anscher,2014;Søgaard,Thomsen,Bossen,Sørensen,&Nørgaard,2013) and combined with an ageing demographic, where more than 60% of cancer patients are over 65, comorbidity and poorer physical and functional health will impact upon future cancer treatment de‐livery and outcomes (Greenlee, Shi, Molmenti, Rundle, & Tsai, 2016). These coexisting health problems are strong indicators for providing prehabilitation to maximise cancer treatment outcomes.
Rehabilitation interventions such as exercise, weight reduction and pharmacotherapy are recognised ways of managing comorbid‐ity‐relatedconditionsaftercancertreatment(Alamuddin,Bakizada,& Wadden, 2016), and there is evidence that smoking cessation (Sitas et al., 2014) reduces adverse treatment effects and improves survival. Preparing patients prior to cancer therapy by improving their overall health status as in prehabilitation could optimise their response to treatment and has important implications for future service delivery (Silver & Baima, 2013). Prehabilitation has been es‐poused as a key component of early recovery in cancer patients and is a term that has been traditionally used to describe interventions for optimising cardiopulmonary reserve prior to cancer surgery, with the aim of improving post‐operative recovery outcomes (Carli
et al., 2017; Silver, 2015; Silver & Baima, 2013). However, prehabil‐itation programmes are also targeting this pre‐treatment period to improve chemotherapy adherence (Le Roy et al., 2016), reduce anxi‐ety (Tsimopoulou et al., 2015) and to provide a stronger platform for post‐treatment rehabilitation aimed at reversing treatment‐related side effects and symptoms, managing comorbidities and enhancing longer‐termhealth‐relatedqualityoflife(Alfano,Ganz,Rowland,&Hahn, 2012; Boereboom, Williams, Leighton, & Lund, 2015; Shun, 2016; Silver, 2014). While fewer studies have been undertaken outside of the surgical context, a growing number of studies are fo‐cusing on different cancer treatments and modes of prehabilitation using exercise, psychological support and nutritional interventions. These studies need to look at longer‐term outcomes beyond the traditional enhanced recovery 30 days post‐treatment outcomes, to understand treatment adherence, mortality, disease prognosis orimpactonhealtheconomics(Stoutetal.,2018).This isthefirstsystematic review to critically review the impact of different preha‐bilitation interventions on long‐term health outcomes (at or beyond 30 days post‐treatment completion) in cancer patients and explore the utility of prehabilitation as a platform for risk management be‐fore and after all cancer treatments.
This review addressed two questions:
1. Whatistheeffectofprehabilitationon≥30dayspost‐treatmentoutcomes including physical functioning, nutrition and patient‐reported outcomes?
2. How can prehabilitation be used to optimise the management of cancer patients with comorbidity or pre‐existing risk factors that are associated with poorer cancer treatment outcomes?
2 | METHODS
2.1 | Data Sources and search method
The review was registered on PROSPERO (CRD42016050296) inter‐national prospective database of systematic reviews. The search was conducted in two stages. In stage one, studies were identified via ab‐stracts through a systematic search strategy for Medline (Pub med), CINAHL (with full text)EMBASEandCochranecentral registerofcontrolled trials. The databases were chosen to identify potentially relevant published studies in the field of medicine, exercise, health and psychosocial care. Search terms were split into two categories “prehabilitation combined with cancer” and terms to identify the na‐ture of prehabilitation such as “exercise, nutrition, psychology and other behavioural interventions,” The full search strategy and MESH terms are provided in supplementary materials. In stage two, other relevant publications were retrieved by reviewing the reference lists of these studies against the eligibility criteria.
Studies selected were published from the period 2000 to February 2017. The following were all excluded from the review: prehabilitation studies with no reported post‐treatment outcomes at 30 days or longer; studies that combined data from previously pub‐lished studies; and abstracts, case studies, conference abstracts and
| 3 of 22FAITHFULL eT AL.
those not in English. Participants included were cancer patients who were treated with any treatment modality and received any form of prehabilitation either in the home or hospital setting. Prehabilitation was defined as a single‐ or multi‐modality intervention that could in‐clude exercise, nutritional support, patient education and/or psycho‐logical therapy. Control was defined as those participant's receiving
usual care as defined in the clinical pathway. Identification of objec‐tive clinical, patient‐reported and delivery outcomes was described at 30 days post‐treatment completion. Comorbidity data at baseline and at completion were also reviewed. Efficacy in relation to 30 days post‐treatment objective physical functioning was explored through meta‐analysis but data were not of sufficient quality to make a
F I G U R E 1 PRISMAstudyselectionflowchart
Records iden�fied through
MEDLINE database
Iden
�fica
�on
Records iden�fied through
other sources
Records screened a�er duplicates removed
n
(n = 1,422)
Records excluded based on �tle and abstract (n = 1,380)
Studies included in thema�c synthesis (n = 22)
Scre
enin
g El
igib
ility
In
clud
ed
Records iden�fied through
PsycINFO database
Records iden�fied through CINAHL
database
Records iden�fied through Embase
database
Records iden�fied throughCENTRAL database
Total number of records (n = 1,970)
Full-text ar�cles assessed for eligibility (n = 42)
Full-text ar�cles excluded, with reasons (n = 20) 1.Not prehabilita�on 2.Not repor�ng on outcomes more than 30 days from treatment); 3. Case study 4. Not repor�ng on cancer treatment
4 of 22 | FAITHFULL eT AL.
TAB
LE 1
Ri
sk o
f bia
s w
as a
sses
sed
by a
n in
terd
isci
plin
ary
rese
arch
team
usi
ng th
e C
ochr
ane
Col
labo
ratio
n's
tool
for a
sses
sing
risk
of b
ias
ROBI
NS‐
I too
l
Refe
renc
eRe
sear
ch d
esig
n
Rand
om s
eque
nce
gene
ratio
nA
lloca
tion
conc
ealm
ent
Blin
ding
of p
artic
ipan
ts a
nd
pers
onne
l Bl
indi
ng o
f out
com
e as
sess
men
tIn
com
plet
e ou
tcom
e da
taSe
lect
ive
outc
ome
repo
rtin
g
Rand
om, f
or e
xam
ple
rand
om n
umbe
r tab
le,
com
pute
r ran
dom
nu
mbe
r gen
erat
or
Part
icip
ants
and
inve
stig
ator
s en
rolli
ng p
artic
ipan
ts c
ould
not
fo
rese
e as
sign
men
t
Out
com
e an
d th
e ou
tcom
e m
easu
rem
ent a
re n
ot li
kely
to b
e in
fluen
ced
by la
ck o
f blin
ding
No
mis
sing
out
com
e da
ta, r
easo
ns fo
r m
issi
ng d
ata
sim
ilar
acro
ss g
roup
s
Stud
y pr
otoc
ol a
vaila
ble
and
all p
re‐s
peci
fied
outc
omes
are
repo
rted
in
the
pre‐
spec
ified
way
Crite
ria 1
Crite
ria 2
Crite
ria 3
Crite
ria 4
Crite
ria 5
Bale
s et
al.
(200
0)RC
TU
ncle
arH
igh
Unc
lear
Unc
lear
Low
Burg
io e
t al.
(200
6)RC
TLo
wH
igh
Low
Unc
lear
Low
Car
li et
al.
(201
0)RC
T st
ratif
ied
rand
omis
atio
nU
ncle
arU
ncle
arH
igh
Mul
tiple
impu
tatio
nsLo
w
Cen
tem
ero
et a
l. (2
010)
RCT
Low
Low
Low
Low
Low
Gill
is e
t al.
(201
4)RC
TLo
wLo
wLo
wM
ultip
le im
puta
tions
Low
Jensenetal.(2014)
RCT
Unc
lear
Unc
lear
Unc
lear
Unc
lear
Hig
h
Jensenetal.(2015)
RCT
Low
Low
Unc
lear
Low
Low
Stef
anel
li et
al.
(201
3)RC
TU
ncle
arU
ncle
arU
ncle
arU
ncle
arLo
w
Barlésietal.(2008)
RCT
Unc
lear
Unc
lear
Unc
lear
Hig
hLo
w
Che
ville
et a
l. (2
015)
RCT
Unc
lear
Unc
lear
Low
Low
Low
Gar
ssen
et a
l. (2
013)
RCT
bloc
k ra
ndom
ised
Unc
lear
Unc
lear
—bl
ock
rand
omis
atio
nLo
wU
ncle
arH
igh
Park
er e
t al.
(200
9)RC
TU
ncle
arU
ncle
ar
Adaptiverandomisation
proc
edur
e ca
lled
min
imis
atio
n
Low
Unc
lear
/hig
hLo
w
Schm
idt e
t al.
(201
5)RC
T bl
ock
rand
omis
edLo
wU
ncle
arU
ncle
arH
igh
Low
Gill
is e
t al.
(201
4)RC
TLo
wLo
wLo
wLo
wLo
w
Mor
iya
(201
5)RC
TLo
wLo
wU
ncle
arLo
wLo
w
Van
Bokh
orst
‐de
Van
der
Schu
er e
t al.
(200
0)RC
TU
ncle
arU
ncle
arLo
wH
igh
Low
| 5 of 22FAITHFULL eT AL.
comparison. The quality of eligible studies was assessed using the PRISMAcriticalappraisalmethods(ShamseerLetal.,2015).Riskofbias was assessed by an interdisciplinary research team using the Cochrane Collaboration's tool for assessing risk of bias ROBINS‐I tool (Sterne et al., 2016). Observational or quasi‐experimental stud‐ies were included as they provided additional information as to the use of prehabilitation interventions.
3 | RESULTS
Sixteen randomised controlled trials (RCT) and six observational studies were included in the narrative synthesis (Figure 1). The qual‐ity of the RCT studies varied considerably with 7 of the 16 studies being considered as having a high risk of bias. Studies were not suf‐ficiently consistent in intervention or outcome data to be included in a meta‐analysis. In many studies reporting of the randomisation processes, lack of allocation concealment to those enrolling, blinding of outcome assessors and poor reporting of missing data may have impacted on study quality (Table 1). Most studies were single‐centre studies. However, one of two multi‐site studies was a three‐arm trial comparing psychological prehabilitation strategies, with participants randomised to stress management, a support group or usual care (Parker et al., 2009). Other studies compared different prehabilita‐tion components head to head as nutritional interventions or psy‐chological approaches. The number of participants within the RCTs rangedfrom48to652,withamedianof88withatotalnumberofsubjects in the review of 2017 (Table 1). Most individual RCTs ana‐lysed fewer than 60% of the sample originally recruited in the study, excluding participants due to comorbidity or inability to undergo car‐diopulmonary exercise testing. Participants were adults with colo‐rectal (Carli et al., 2010; Cheville et al., 2015; Gillis et al., ; Moriya, 2015) lung (Barlési et al., 2008; Stefanelli et al., 2013), head andneck (Van Bokhorst‐de Van der Schuer et al., 2000), breast (Garssen etal.,2013),bladder (Jensen,KrintelPetersen,Jensen,Lausten,&Borre,2014;Jensen,Petersen,Jensen,Laustsen,&Borre,2015)andprostate (Bales et al., 2000; Burgio et al., 2006; Parker et al., 2009) cancer or included individuals with a range of cancers (Schmidt et al., 2015). Trial designs were primarily feasibility studies, and there‐fore, the studies were rarely powered to determine the efficacy of prehabilitation on post‐treatment recovery outcomes. The primary endpoint was predominantly objective physical function prior to treatment with the secondary endpoints described at 1–6 months post‐intervention. Only four (25%) of the authors fully reported par‐ticipantcomorbiditiesatbaseline(Burgioetal.,2006;Jensenetal.,2015; Schmidt et al., 2015; Van Bokhorst‐de Van der Schuer et al., 2000) while two actively excluded participants with comorbidities possibly due to the intensity of the exercise programme (Carli et al., 2010; Stefanelli et al., 2013).
The designs of the six observational studies were either case‐controlled cohort, historical controls or quasi‐experimental. Studies were primarily feasibility studies, and participant numbers were small,rangingfrom35to87withatotalof289participants.Studies
included individuals with breast cancer (Baima et al., 2015), lung can‐cer(Jonesetal.,2007;Peddleetal.,2009;Sekineetal.,2005),col‐orectal cancer (Li et al., 2013) and prostate cancer (Sueppel, Kreder, & See, 2001).
Comorbidities were only reported in three of the studies at base‐line, with ill health being cited as a contributing factor to difficulties with recruitment rather than this being recorded as an outcome. Several studies did not report attrition (Sekine et al., 2005; Sueppel et al., 2001), and among those that did attrition rates ranged from 0% to 52%. The number and combination of prehabilitation modal‐ities varied considerably across studies, ranging from 1 to 3 across individual RCTs and observational studies (Tables 2 and 3).
Most (16/22) studies included an exercise modality, either as a stand‐alone prehabilitation intervention or in combination. Four studies examined the effects of pelvic floor training in men with prostate cancer over a varying number of weeks before radical pros‐tatectomy (Bales et al., 2000; Burgio et al., 2006; Centemero et al., 2010; Sueppel et al., 2001). These were predominantly home‐based exercise programmes with some level of instruction and supervision and/or biofeedback training. Two studies incorporated supervised therapeutic pulmonary exercises (in conjunction with more conven‐tional conditioning exercise) in lung cancer patients in the 2–3 weeks prior to surgery (Sekine et al., 2005; Stefanelli et al., 2013). These exercises were performed on 5–7 days per week and included in‐centive spirometry, abdominal breathing, huffing and coughing, and respiratory exercises on a bench, mattress pad and wall bars. Finally, a study in breast cancer patients investigated the feasibility of ther‐apeutic shoulder mobility exercises in the 2–4 weeks before surgery, comparing in‐person teaching with video‐only teaching (Baima et al., 2015). Both methods were shown to be feasible with high adher‐ence(≥75%).Otherstudiesinvestigatedtheeffectsofconventionalforms of exercise conditioning for improving cardiopulmonary fit‐nessand/ormuscularstrengthoverdurationsof2–8weeks,thoughmost programmes were of 2‐ to 4‐week duration (Tables 2 and 3). Allbutoneofthesestudiesimplementedexerciseprehabilitationinthe time period before colorectal, lung or bladder cancer surgery, whereas the remaining study (Cheville et al., 2015) focused on ad‐herence to chemoradiotherapy in patients with gastrointestinal can‐cers. Home‐based programmes generally consisted of aerobic and resistance exercise on at least three days per week with varying de‐grees of face‐to‐face supervision and telephone support (Carli et al., 2010;Gillisetal.,2014;Jensenetal.,;Lietal.,2013).Instructionson both the frequency and intensity of aerobic exercise were gener‐ally provided, and in some cases, participants used heart rate moni‐tors and perceived exertion scales to self‐assess their level of effort (Gillis et al., 2014; Li et al., 2013). Studies of more closely supervised 2‐ to 6‐week programmes of exercise prehabilitation involved vig‐orous intensitycycleergometry in lung(Jonesetal.,2007;Peddleet al., 2009) and rectal cancer patients (West et al., 2015) prior to surgery and isokinetic muscle strengthening exercises in patients with gastrointestinal cancers during chemoradiotherapy (Cheville et al., 2015). Two further studies included vigorous gym‐based aero‐bic exercise (Stefanelli et al., 2013) or walking exercise (5,000 steps/
6 of 22 | FAITHFULL eT AL.
TAB
LE 2
Ra
ndom
ised
con
trol
led
tria
ls (R
CTs
) of p
reha
bilit
atio
n an
d cr
itica
l ana
lysi
s
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Bale
s et
al.
(200
0)Fr
eque
ncy:
2–4
wee
ks p
rior t
o su
rger
yIn
tens
ity: n
urse
‐led
biof
eedb
ack,
10–15repetitionsAdvisedto
prac
tice
4× p
er d
ayTi
min
g 45
min
Type
: pel
vic
floor
mus
cle
exer
cise
plu
s bi
ofee
dbac
k fo
llow
ed b
y po
st‐o
p PF
M e
xerc
ises
Writ
ten
and
brie
f ver
bal
inst
ruct
ions
on
how
to
perf
orm
pel
vic
floor
m
uscl
e ex
erci
ses
100
men
und
ergo
ing
radi
cal p
rost
atec
tom
yM
ean
age
inte
rven
tion
60.9
yea
rs a
nd c
ontr
ol
59.3
yea
rs.
Pros
tate
can
cer s
tage
s T1
c‐T2
cC
omor
bidi
ty n
ot re
port
ed
Ever
y m
onth
for
6 m
onth
s po
st‐s
urge
ry
3%
6%By
6 m
onth
s fo
llow
ing
radi
cal p
rost
atec
tom
y, th
e in
cide
nce
of
urin
ary
cont
inen
ce in
the
biof
eedb
ack
and
cont
rol g
roup
s w
as
94%
and
96%
, res
pect
ivel
y.N
o di
ffer
ence
in p
atie
nts
who
rece
ived
bio
feed
back
pre
‐op
and
thos
e w
ho d
id n
ot T
here
was
no
obje
ctiv
e m
easu
re, j
ust n
umbe
r of
wet
dia
pers
(vs.
wei
ght o
f dia
per);
unc
lear
abo
ut c
hara
cter
is‐
tics
of th
ose
who
dro
pped
out
, unk
now
n pe
lvic
floo
r mus
cle
stre
ngth
prio
r to
unde
rtak
ing
stud
y
Barlé
si e
t al.
(2008)
Freq
uenc
y: u
ncle
arIn
tens
ity: u
ncle
arTi
min
g: p
rior t
o su
rger
yTy
pe: a
dditi
onal
ora
l plu
s w
ritte
n in
form
atio
n in
clud
ing
asso
ciat
ed
sym
ptom
s
Ora
l inf
orm
atio
n on
ly
desc
ribin
g th
e di
seas
e an
d its
ass
ocia
ted
surg
ery
and
outc
omes
75 p
atie
nts
with
NSC
LC
unde
rgoi
ng th
orac
ic
surg
ery
Com
orbi
dity
not
repo
rted
Base
line
and
3 m
onth
s26
%Q
oL s
core
s (b
asel
ine,
3 m
onth
s) w
ere
com
para
ble
betw
een
both
gr
oups
.Pa
tient
s re
ceiv
ing
oral
plu
s w
ritte
n in
form
atio
n w
ere
sign
ifica
ntly
di
ssat
isfie
d re
late
d to
sev
eral
asp
ects
of c
are
rega
rdin
g st
aff a
s w
ell a
s th
e st
ruct
ure.
The
info
rmat
ion
grou
p si
gnifi
cant
ly in
fluen
ced
satis
fact
ion
leve
ls
at m
ultiv
aria
te a
naly
sis
(sta
ndar
dise
d be
ta c
oeff
icie
nt, 0
.26,
p
= 0.
04)
Burg
io e
t al.
(200
6)Fr
eque
ncy:
initi
ated
1 w
eek
prio
r to
surg
ery
Inte
nsity
dai
ly 4
5 pe
lvic
floo
r exe
rcis
esTi
min
g: o
ne p
re‐o
pera
tive
sess
ion
Type
: bio
feed
back
plu
s as
sist
ed
beha
viou
ral t
rain
ing
Hom
e‐ba
sed
exer
cise
Usu
al c
are
125
men
und
ergo
ing
surg
ery
Mea
n ag
e 60
.9 ±
6.9
yea
rs.
Pros
tate
can
cer
Com
orbi
dity
repo
rted
6 m
onth
s’ po
st‐s
urge
ry10
%At6months:
Diff
eren
ce b
etw
een
the
grou
ps in
the
prop
ortio
n of
men
re
mai
ning
inco
ntin
ent w
as 2
0.03
% (h
ighe
r in
the
inte
rven
tion
grou
p) (9
5% C
I 6.0
2% to
34.
63%
) (p
< 0.
04).
Seve
re/c
ontin
ual l
eaka
ge w
as s
till p
rese
nt in
19.
6% o
f con
trol
s co
mpa
red
to 5
.9%
of t
hose
in in
terv
entio
n gr
oup
(p <
0.0
4).
Inte
rven
tion
grou
p ha
d a
• hi
gher
pro
port
ion
of d
ry d
ays
(p <
0.0
4),
• lo
wer
pro
port
ion
usin
g pa
ds (p
< 0
.05)
. N
o gr
oup
diff
eren
ces
wer
e fo
und
in li
fest
yle
varia
bles
,•
inco
ntin
ence
impa
ct (p
= 0
.36,
• ps
ycho
logi
cal d
istr
ess
(p =
0.6
9)•
qual
ity o
f life
(p=0.31to0.89).
Unc
lear
how
long
pro
vide
d an
d th
e in
tens
ity o
f the
exe
rcis
es
Car
li et
al.
(201
0)Fr
eque
ncy:
ave
rage
52
days
prio
r to
surg
ery
Inte
nsity
: hig
h‐in
tens
ity e
xerc
ise
Tim
ing
thre
e tim
es p
er w
eek
Type
: pre
scrib
ed s
tatio
nary
cyc
ling
(dai
ly) w
ith s
tren
gthe
ning
pre
scrib
ed
Wal
k/br
eath
ing
grou
p:
reco
mm
enda
tions
to
wal
k da
ily a
nd p
erfo
rm
foot
and
ank
le
exer
cise
s to
enh
ance
lo
wer
‐ext
rem
ity
circ
ulat
ion
as w
ell a
s br
eath
ing
exer
cise
s
112
patie
nts
unde
rgoi
ng
colo
rect
alsu
rger
y.M
ean
age
60 (S
D 1
6)Pa
rtic
ipan
ts w
ith
com
orbi
ditie
s gr
ade
IV o
r V
wer
e ex
clud
ed fr
om
stud
y or
if u
nabl
e to
co
mpl
ete
test
ing
proc
edur
e
10 w
eeks
’ po
st‐s
urge
ry16
%Im
prov
emen
t in
wal
king
cap
acity
in w
alk/
brea
thin
g (4
7%) v
ersu
s bi
ke/s
tren
gthe
ning
pre
‐sur
gery
(22%
). Bu
t not
sus
tain
ed o
ver
time
• M
ean
peak
VO
2 im
prov
ed in
bot
h gr
oups
: Bik
e/st
reng
then
ing
134
ml/
min
(p =
0.0
03) v
ersu
s w
alk
brea
thin
g 11
2 m
l/m
in
(p =
0.0
07) b
ut n
ot o
ver t
ime.
•Anxietyconsiderablyreducedaftersurgerybutdidnotchange
in e
ither
gro
up o
ver t
he p
reha
bilit
atio
n pe
riod.
• D
epre
ssio
n im
prov
ed fo
r the
bik
e/st
reng
then
ing
grou
p ov
er
the
preh
abili
tatio
n pe
riod.
• Ex
erci
se p
artic
ipat
ion
bike
/str
engt
heni
ng g
roup
> w
alk/
brea
thin
g gr
oup
(p =
0.0
75).
Low
er e
xerc
ise
had
bett
er o
utco
mes
bec
ause
of l
ess
drop
outs
, po
or c
ompl
ianc
e in
the
high
er in
tens
ity g
roup
may
hav
e be
en
too
hard
for s
uch
patie
nts
(Con
tinue
s)
| 7 of 22FAITHFULL eT AL.
TAB
LE 2
(C
ontin
ued)
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Cen
tem
ero
et a
l. (2
010)
Freq
uenc
y: s
tart
ed 3
0 da
ys b
efor
e su
rger
y 2×
per
wee
kIn
tens
ity: p
hysi
othe
rapi
st
enco
urag
emen
tTi
min
g: 3
0 m
inTy
pe: p
elvi
c flo
or m
uscl
e ex
erci
ses
at
hosp
ital a
nd a
t hom
e
Post
‐ope
rativ
e pe
lvic
flo
or m
uscl
e ex
erci
ses
48hraftercatheter
rem
oval
118malesundergoing
surg
ery.
46–68yearsold.
Pros
tate
can
cer
Com
orbi
dity
not
repo
rted
3 m
onth
s17
% d
id
not s
tart
st
udy
but
wer
e el
igib
le
Con
tinen
ce in
pre
‐ope
rativ
e gr
oup
was
59.
3% v
ersu
s po
st‐
operativegroup37.3%(p<0.028)
•ICSmaleSFmeanscoreinpre‐operativegroup8.1versus
post
‐ope
rativ
e gr
oup
12.2
.•
Stud
y fo
und
that
pre
‐ope
rativ
e PF
ME
impr
oved
qua
lity
of li
fe
(The
ICFS
is a
sym
ptom
‐bas
ed to
ol)
No
deta
il re
‐adh
eren
ce to
exe
rcis
es. T
he q
uest
ion
whe
ther
the
pre‐
oper
ativ
e or
pos
t‐op
erat
ive
had
mos
t eff
ect i
s un
clea
r. D
iffer
ence
s pe
rsis
ted
for u
p to
6 m
onth
s at
1 y
ear t
here
was
no
diff
eren
ce
Che
ville
et a
l. (2
015)
Freq
uenc
y: 2
–3×
per w
eek
Inte
nsity
:Ti
min
g:(6–8sessions)
Type
: led
by
psyc
hiat
rist i
nclu
ded
soci
al, c
ogni
tive,
em
otio
nal c
are
via
exer
cise
, edu
catio
n an
d re
laxa
tion
Usu
al c
are
61 s
tudy
sam
ple
Wom
en, m
ean
age
61.2
Com
orbi
dity
not
repo
rted
30‐d
ay
read
mis
sion
Not
re
port
edM
ore
patie
nts
in th
e in
terv
entio
n co
mpl
eted
che
mot
hera
py
(p =
0.0
03) t
han
cont
rol
• In
terv
entio
n gr
oup
had
sign
ifica
ntly
few
er tr
eatm
ent
hosp
italis
atio
ns (p
= 0
.001
)•
No
diff
eren
ce in
oth
er m
easu
res
Ther
e ar
e no
dat
a ca
ptur
e on
med
icat
ions
or f
unct
iona
l hea
lth
stat
us. N
o pa
tient
repo
rted
out
com
es o
r psy
chol
ogic
al m
easu
res
all d
ata
capt
ure
was
thro
ugh
EMR
retr
ospe
ctiv
e re
cord
s
Gar
ssen
et a
l. (2
013)
Freq
uenc
y: fo
ur s
essi
ons
5 an
d 1
day
prio
r to
surg
ery
with
ses
sion
2 a
nd
30 d
ays
post
‐sur
gery
Inte
nsity
:Ti
min
g: 4
0–60
min
Type
: str
ess
man
agem
ent t
rain
ing
deliv
ered
by
clin
ical
psy
chol
ogis
t—re
laxa
tion,
gui
ded
imag
ery
tech
niqu
es, a
nd c
ouns
ellin
g
Usu
al c
are
70 w
omen
und
ergo
ing
surg
ery
for b
reas
t can
cer
Inte
rven
tion
mea
n ag
e 52
yea
rs c
ontr
ol g
roup
m
ean
age
54 y
ears
Com
orbi
dity
par
tially
re
port
ed (B
MI,
alco
hol
use)
30–9
0 da
ys
post
‐sur
gery
18%
Onl
y 57
%
of e
ligib
le
patie
nts
finis
hed
stud
y
At3months’post‐surgerycomparedtobaseline,theintervention
grou
p ha
d:•
Sign
ifica
nt d
iffer
ence
at 1
mon
th in
dep
ress
ion
• no
sig
nific
ant d
iffer
ence
in q
ualit
y of
life
• no
sig
nific
ant d
iffer
ence
in w
ellb
eing
• pa
in n
ot m
easu
red
at 3
mon
ths
• co
ntro
l gro
up m
ore
com
plai
nts
than
inte
rven
tion
grou
p (0
.001
< p
<0.0
1).
At3monthspost‐opmeasureswillbeaffectedbystartof
adju
vant
trea
tmen
t (an
d no
info
rmat
ion
repo
rted
on
this
). Ex
perie
nce
of c
ontr
ol m
easu
red
by a
utho
r des
igne
d 4‐
item
qu
estio
nnai
res
(un
valid
ated
mea
sure
s). U
nabl
e to
diff
eren
tiate
ef
fect
of i
nter
vent
ion
cont
ent o
r psy
chol
ogis
t int
erve
ntio
n.Th
e st
udy
pow
er is
not
cle
ar a
gain
st it
s pr
imar
y ou
tcom
e.
Targ
eted
inte
rven
tion.
The
diff
eren
ces
betw
een
grou
ps a
t 3
mon
ths
are
not s
igni
fican
t
(Con
tinue
s)
8 of 22 | FAITHFULL eT AL.
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Gill
is e
t al.
(201
4)Fr
eque
ncy:24days−3daysperweek
Inte
nsity
: mod
erat
e ae
robi
c an
d re
sist
ance
exe
rcis
es,
Tim
ing:
50
min
Type
hom
e‐ba
sed
unsu
perv
ised
in
itial
ly p
erso
nalis
ed to
the
indi
vidu
al. N
utrit
ion
coun
selli
ng w
ith
prot
ein
supp
lem
enta
tion
Cop
ing
stra
tegi
es to
redu
ce a
nxie
ty
and
prom
ote
adhe
renc
e w
ith
exer
cise
s pr
ovid
ed o
n a
CD
Reha
bilit
atio
n gr
oup
or
8weekspost‐opera‐
tivel
y (s
ame
as
inte
rven
tion
but a
fter
su
rger
y)
89patientsundergoing
surg
ery
for c
olor
ecta
l ca
ncer
preh
ab m
ean
age
= 65
.7
(13.
6); r
ehab
mea
n =
66.0
(9
.1)
Com
orbi
dity
fully
repo
rted
8weeks’
post
‐op
13%
Diff
eren
ce b
etw
een
base
line
and
follo
w‐u
p in
pre
habi
litat
ion
grou
p. M
ean
diff
eren
t 45.
4 m
(95%
CI,
13.9
–77.
0)•
Base
line:
Pre
hab
421
m (S
D, 1
20.0
) Reh
ab 4
25 m
(SD,83.8)
•Pre‐treatment:Prehab+25.2(50.2)Rehab−16.4(46.0)
p =
0.00
1•
50%
of p
atie
nts
in b
oth
grou
ps re
mai
ned
mor
e th
an 2
0 m
be
low
bas
elin
e•At8weeks,prehab+23.4(54.8)rehab−21.8(80.7).p
= 0
.020
• C
ompl
icat
ion
rate
s an
d le
ngth
of h
ospi
tal s
tay
wer
e si
mila
r in
preh
abili
tatio
n an
d re
habi
litat
ion
grou
ps.
Achangeof20misconsideredclinicallymeaningfulasthisisthe
estim
ated
mea
sure
men
t of c
omm
unity
‐dw
ellin
g el
derly
Lim
itatio
n of
the
stud
y is
mis
sing
dat
a an
d un
clea
r whi
ch m
odal
ity
of p
reha
bilit
atio
n re
spon
sibl
e fo
r out
com
es
Gill
is e
t al.
(201
6)Fr
eque
ncy:
4 w
eeks
prio
r to
surg
ery:
Inte
nsity
: dai
ly in
terv
entio
nTi
min
g: 9
0 m
in p
er d
ayTy
pe: i
ndiv
idua
lised
nut
ritio
n co
unse
lling
with
dai
ly w
hey
prot
ein
supp
lem
enta
tion
Indi
vidu
alis
ed n
utrit
ion
coun
selli
ng w
ith a
no
n‐nu
triti
ve p
lace
bo
43 p
atie
nts
unde
rgoi
ng
surg
ical
trea
tmen
t.M
ean
age
67.6
yea
rs (S
D
11.5
). M
ean
age
in
plac
ebo
grou
p (6
9.1
year
s (S
D 9
.4)
Com
orbi
ditie
s pa
rtia
lly
repo
rted
4–8weeks
post
‐op
10%
Beforesurgeryimprovementinwheygroup20.8m(S
D 4
2.6
m)
and
in p
lace
bo g
roup
(1.2
m (S
D 6
5.5
m) (
p =
0.27
).•
Reco
very
rate
s w
ere
sim
ilar b
etw
een
grou
ps in
the
4‐w
eeks
po
st‐s
urge
ry (p=0.81).
• C
omm
ent:
inte
rven
tion
focu
sed
on b
uild
ing
stre
ngth
. Foc
us o
n up
per‐
body
str
engt
h an
d no
t low
er b
ody.
Pos
t‐in
terv
entio
n la
ck o
f nut
ritio
n m
ay im
pact
on
sim
ilar g
roup
traj
ecto
ries.
• Pr
e‐su
rger
y re
sults
are
sig
nific
ant b
ut n
ot s
usta
ined
at 4
wee
ks6
MW
T da
ta m
issi
ng p
re‐o
p fo
r fou
r pat
ient
s (tw
o pl
aceb
o, tw
o w
hey)
and
12
post
‐op
(four
pla
cebo
, eig
ht w
hey)
, ana
lysi
s ba
sed
on 3
2 pa
rtic
ipan
ts. I
f pro
tein
requ
ired
to im
prov
e m
uscl
e fu
nctio
nal c
apac
ity, p
resu
mab
ly p
rote
in s
uppl
emen
tatio
n sh
ould
be
con
tinue
d po
st‐o
p fo
r fun
ctio
nal c
apac
ity to
be
mai
ntai
ned?
Th
is s
tudy
indi
cate
s th
at e
ffec
ts m
ay o
nly
be s
hort
‐ter
m (i
.e.
4 w
eeks
to d
ay o
f sur
gery
, and
ass
ocia
ted
with
dur
atio
n of
in
terv
entio
n)
TAB
LE 2
(C
ontin
ued)
(Con
tinue
s)
| 9 of 22FAITHFULL eT AL.
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Jensenetal.
(201
4)Fr
eque
ncy:
2 w
eeks
prio
r to
surg
ery:
Inte
nsity
: 15‐
min
ste
p tr
aini
ngTi
min
g: 2
× pe
r day
Type
: writ
ten
info
rmat
ion
and
mot
ivat
ion
hom
e ba
sed
Pt ta
ilore
d ex
erci
ses
for s
ix m
uscl
e st
reng
th a
nd e
ndur
ance
Stan
dard
ised
pos
t‐op
erat
ive
mob
ilisa
tion
Stan
dard
ised
nut
ritio
nal
scre
enin
g an
d co
unse
lling
.St
anda
rdis
ed
post
‐ope
rativ
e m
obili
satio
n w
as
enco
urag
ed a
t lea
st 2
× at
30
min
day
129
patie
nts u
nder
goin
g ra
dica
l cys
tect
omy
(ana
lysi
s bas
ed o
n 10
0 (in
terv
entio
n 47
, sta
ndar
d 53
)Bl
adde
r can
cer
Com
orbi
dity
fully
repo
rted
4 m
onth
s’ po
st‐s
urge
ry41
%Th
ere
was
no
sign
ifica
nt d
iffer
ence
in L
OS
and
num
ber o
f adv
erse
ev
ents
.•
Phys
ical
cap
acity
was
sig
nific
antly
impr
oved
(p0.
02) a
nd m
ean
wal
king
dis
tanc
e at
7 d
ays’
post
‐op.
•Atfollow‐upbothgroupshadregainedphysicalcapacityand
no d
iffer
ence
was
see
n.•
Patie
nt ta
ilore
d in
terv
entio
n bu
t unc
lear
as
to h
ow th
is w
as
personalised.Abstracthaslittleinformationre‐intervention.
Justoverhalf(55%)completedtheprehabprogrammeat100%,
59%
fulfi
lled
75%
. It w
ould
hav
e be
en u
sefu
l to
com
pare
gro
ups
on 6
MW
T ra
ther
than
LO
S as
prim
ary
outc
ome
mea
sure
Jensenetal.
(201
5)Fr
eque
ncy:
2×
daily
Inte
nsity
: pro
gres
sive
str
engt
h an
d en
dura
nce
exer
cise
sTi
min
g da
ilyTy
pe: p
re‐o
pera
tive
hom
e‐ba
sed
supe
rvis
ed e
xerc
ise
prog
ram
me
and
post
‐ope
rativ
e an
d pr
ogre
ssiv
e po
st‐o
pera
tive
mob
ilisa
tion
Fast
trac
k Pa
tient
ed
ucat
ion
coun
selli
ng
on c
hoic
e of
urin
ary
inte
rven
tion,
pre
‐op
prep
arat
ion,
pai
n co
ntro
l and
nut
ritio
n
107
patie
nts
unde
rgoi
ng
surg
ical
trea
tmen
t for
bl
adde
r can
cer.
Mea
n ag
e in
terv
entio
n gr
oup
66 y
ears
, mea
n ag
e co
ntro
l gro
up 7
1 ye
ars.
Blad
der c
ance
rC
omor
bidi
ties
fully
re
port
ed
4 m
onth
s’ po
st‐s
urge
ry7%
at
triti
on55
%
adhe
r‐en
ce
Seve
rity
of c
ompl
icat
ions
: No
signi
fican
t diff
eren
ce w
as fo
und
in
the
inci
denc
e (p
= 0
.47)
or s
ever
ity (p
= 0
.64)
of c
ompl
icat
ions
be
twee
n th
e tr
eatm
ent g
roup
s at 9
0 da
ys p
ost‐
oper
ativ
ely,
or i
n re
adm
issio
n w
ithin
30
days
(p =
0.4
9).
AbilitytoperformADL:Themediantimewas3daysinthe
inte
rven
tion
grou
p, c
ompa
red
with
4 d
ays i
n th
e st
anda
rd g
roup
(p
< 0
.05)
.Po
st‐o
p m
obili
satio
n: si
gnifi
cant
ly h
ighe
r in
the
inte
rven
tion
grou
p,
reporting4,806mwalked(95%CI4,075–5,536m),comparedto
thestandardgroupwith2,906mwalked(95%CI2,408–3,404m)
(p <
0.0
01) a
t 7 d
ays
Sign
ifica
nce
in 4
‐mon
th o
utco
mes
bet
wee
n gr
oups
not
see
n
Mor
iya
(201
5)In
terv
entio
n 1
Freq
uenc
y: 5
day
s pr
e‐op
erat
ivel
yIn
tens
ity: h
igh
dose
750
ml/d
ayTi
min
g: d
aily
Type
: im
mun
e‐en
hanc
ing
diet
(IED
) (enrichedwitharginine,omega−3
fattyacidsandRNA)andnormal
food
Inte
rven
tion
2.In
tens
ity: l
ow‐d
ose
250
ml/d
ay
imm
une‐
enha
ncin
g di
et
Con
trol
gro
up –
nor
mal
fo
od88patientsundergoing
surg
ery
for c
olor
ecta
l ca
ncer
Mea
n ag
e in
terv
entio
n 64.7(2.3)control63.8(2)
Com
orbi
dity
not
repo
rted
9–13
3 m
onth
s af
ter s
urge
ryN
ot
repo
rted
Inci
sion
al S
SI ra
tes
in th
e IE
D g
roup
s w
ere
sign
ifica
ntly
low
er in
th
e in
terv
entio
n gr
oup
than
in th
e C
ontr
ol g
roup
. (0%
*, 0%
* an
d 17
%) (
*p <
0.0
1 vs
. Con
trol
).Th
e in
cide
nces
of t
he in
fect
ions
not
invo
lvin
g th
e su
rgic
al s
ite
(non
‐SSI
) and
the
leng
ths
of h
ospi
tal s
tay
wer
e si
mila
r am
ong
the
thre
e gr
oups
. No
sign
ifica
nt d
iffer
ence
s w
ere
obse
rved
in
RFS
or D
SS
(Con
tinue
s)
TAB
LE 2
(C
ontin
ued)
10 of 22 | FAITHFULL eT AL.
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Park
er e
t al.
(200
9)Fr
eque
ncy:
1–2
wee
ks p
re‐o
pIn
tens
ity:
Tim
ing
2× 6
0–90
min
ses
sion
s pl
us 2
bo
oste
r ses
sion
s on
mor
ning
of
surgeryand48hrpost‐surgery)
Type
:In
terv
entio
n 1.
Str
ess
man
agem
ent
(SM
) inc
ludi
ng d
iaph
ragm
atic
br
eath
ing
and
guid
ed im
ager
y in
divi
dual
ses
sion
s w
ith c
linic
al
psyc
holo
gist
,In
terv
entio
n 2
Supportiveattention(SA)group
disc
usse
d th
eir c
once
rns
abou
t the
up
com
ing
surg
ery
and
had
a se
mi‐s
truc
ture
d m
edic
al in
terv
iew
Stan
dard
car
e (n
o m
eetin
gs w
ith c
linic
al
psyc
holo
gist
)
159
men
und
ergo
ing
surg
ery
for p
rost
ate
canc
er.
Mea
n ag
e 60
.9 (5
.9)
Com
orbi
ditie
s no
t rep
orte
d
6–12
mon
ths
post
‐sur
gery
34%
Post
‐tre
atm
ent i
mpr
ovem
ents
of i
nter
vent
ion
on m
ood
dist
urba
nce
(p =
0.0
2) w
ith th
e st
ress
man
agem
ent g
roup
with
no
sig
nific
ant d
iffer
ence
s be
twee
n gr
oups
in a
ny o
f the
as
sess
men
t tim
es b
etw
een
grou
ps o
ver t
ime.
The
mix
ed m
odel
ana
lysi
s ta
rget
ed th
erap
ies.
Diff
eren
ces
in
moo
d w
ere
smal
l and
alth
ough
sig
nific
ant a
re n
ot c
linic
ally
significant.At1year,patientshadbetterphysicalfunction
(SF36)butthiswasself‐reported.Atargetedinterventionon
thos
e in
divi
dual
s w
ith h
ighe
r str
ess
may
be
mor
e be
nefic
ial i
n te
rms
of e
ffec
t siz
e.M
en in
SM
gro
up h
ad s
igni
fican
tly h
ighe
r phy
sica
l com
pone
nt
sum
mar
y sc
ore
on S
F35
than
men
is S
C gr
oup
at o
ne y
ear
(p =
0.0
009)
, but
no
diff
eren
ce in
men
tal c
ompo
nent
sum
mar
y sc
ore
or p
rost
ate‐
spec
ific
Qol
in P
CI.
The
stud
y ex
clud
ed
emot
iona
lly d
istr
esse
d m
en w
ho m
ay b
enef
it fr
om s
uch
an
inte
rven
tion
Schm
idt e
t al.
(201
5)Fr
eque
ncy:
1 d
ay p
re‐o
pera
tivel
yIn
tens
ity:
Tim
ing:
7 d
ays
Type
info
rmat
ion
book
let l
ifest
yle
advi
ce, m
obili
satio
n, n
utrit
ion
and
diar
y ke
epin
g
Stan
dard
car
e—in
form
a‐tio
n re
gard
ing
surg
ical
an
d an
aest
hesi
olog
y ris
ks a
nd p
roce
dure
s
652
patie
nt’s
unde
rgoi
ng
elec
tive
surg
ery
for g
astr
oint
estin
al,
geni
tour
inar
y, a
nd
thor
acic
can
cer
65 y
ears
of a
geC
omor
bidi
ties
repo
rted
3 –1
2 m
onth
s af
ter s
urge
ry15
%C
ompl
icat
ions
: Occ
urre
nce
and
seve
rity
of c
ompl
icat
ions
wer
e co
mpa
rabl
e in
bot
h gr
oups
, alth
ough
sev
ere
haem
orrh
age
occu
rred
sig
nific
antly
mor
e of
ten
in th
e in
terv
entio
n gr
oup
(6.7
% v
s. 2
.5%
; p =
0.0
1).
• LO
S: n
o si
gnifi
cant
diff
eren
ce b
etw
een
both
gro
ups
(p =
0.9
9).
• H
RQoL
: no
sign
ifica
nt d
iffer
ence
bet
wee
n th
e gl
obal
HRQ
oL
12 m
onth
s af
ter s
urge
ry in
the
inte
rven
tion
and
in th
e co
ntro
l gr
oup.
• Po
st‐o
pera
tive
stre
ss: (
mob
ilisa
tion,
PO
NV
and
post
‐ope
rativ
e pa
in).
Patie
nts i
n th
e in
terv
entio
n gr
oup
repo
rted
less
pai
n on
the
firstpost‐operativeday(75.2%vs.82.3%,p
= 0
.03)
. The
re w
ere
no d
iffer
ence
s reg
ardi
ng m
obili
satio
n w
ithin
the
first
24
hr (6
9.2%
vs
. 70.
4%, p=0.73),orPONVwithinthefirstfivedays(52.8%vs.
56.4
%, p
= 0
.39)
.•
Dep
ress
ion:
The
re w
as n
o di
ffer
ence
in th
e ge
riatr
ic d
epre
ssio
n sc
ale
betw
een
inte
rven
tion
and
cont
rol g
roup
s at d
isch
arge
(p=0.86).
• Re
adm
issi
on: T
he re
adm
issi
on ra
te w
ithin
90
days
was
slig
htly
hi
gher
for p
atie
nts
in th
e in
terv
entio
n gr
oup
(p =
0.7
0).
In‐h
ospi
tal l
engt
h of
sta
y at
read
mis
sion
was
sho
rter
than
in
the
stan
dard
car
e gr
oup
with
out r
each
ing
stat
istic
al
sign
ifica
nce
(p =
0.2
2).
• M
orta
lity:
The
ove
rall
mor
talit
y di
d no
t diff
er s
igni
fican
tly
betw
een
the
two
grou
ps (L
og‐R
ank‐
test
p =
0.1
97).
Patie
nt e
mpo
wer
men
t fai
led
to s
hort
ed L
OS
or H
RQO
L. T
his
type
of
inte
rven
tion
coul
d en
hanc
e qu
ality
of c
are
in re
gard
to p
ain,
an
d si
nce
over
‐tre
atm
ent o
f pai
n is
par
ticul
arly
har
mfu
l for
el
derly
pat
ient
s, p
atie
nt s
afel
y ca
n th
us b
e im
prov
ed. P
re‐
oper
ativ
e in
form
atio
n w
as re
ceiv
ed w
ell b
y pa
tient
s w
ho w
ere
cogn
itive
ly a
nd p
hysi
cally
fit
TAB
LE 2
(C
ontin
ued)
(Con
tinue
s)
| 11 of 22FAITHFULL eT AL.
Refe
renc
eIn
terv
entio
n de
scrip
tion
Cont
rol g
roup
de
scrip
tion
Sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Stef
anel
li et
al.
(201
3)Fr
eque
ncy:
3 w
eeks
pre
‐ope
rativ
ely
Inte
nsity
: hig
h‐in
tens
ity tr
aini
ngTi
min
g: 1
5 ×
3‐hr
ses
sion
s w
eekd
ays
Type
: out
patie
nt in
tens
ive
pulm
onar
y re
habi
litat
ion
(PRP
) bas
ed o
n of
bot
h up
per‐
and
low
er‐li
mb
mus
cles
Con
trol
sur
gery
ac
cord
ing
to th
e no
rmal
sta
ndar
d pr
e‐op
erat
ive
prot
ocol
40 N
SCL
and
CO
PD
unde
rgoi
ng lo
bect
omy
Age>75
Excl
uded
pat
ient
s w
ith
com
orbi
dity
60 d
ays
afte
r su
rger
yN
ot
repo
rted
AsignificantdifferencewasobservedbothatT1andT2.
In p
reha
bilit
atio
n gr
oup,
pea
k V
O2 i
mpr
oves
sig
nific
antly
from
T0
to T
1, p
< 0
.001
and
det
erio
rate
s fr
om T
1 to
T2,
p <
0.0
01 in
co
ntro
l rev
ertin
g to
a s
imila
r val
ue to
that
at T
0.•
Con
trol
gro
up p
eak
VO
2 did
not
cha
nge
from
T0
to T
1 an
d si
gnifi
cant
ly d
eter
iora
tes
from
T1
to•
T2: p
< 0
.000
01.
• FE
V1
NS
T0, T
1, T
2C
urre
ntly
, oth
er s
tudi
es a
re n
eede
d to
dem
onst
rate
that
the
patie
nts w
ho u
nder
go p
re‐o
pera
tive
PRP
coul
d ha
ve a
lso
a be
tter
qu
ality
of l
ife, l
ess p
ost‐
oper
ativ
e co
mpl
icat
ions
and
a lo
nger
su
rviv
al a
fter
sur
gery
.G
ood
for C
PET
VS
6 M
WT
com
paris
on
Van
Bokh
orst
‐de
Van
der
Sc
huer
et a
l. (2
000)
Freq
uenc
y: 7
–10
days
pre
‐ope
rativ
ely
plus
14
days
pos
t‐op
Inte
nsity
: 150
% o
f bas
al e
nerg
y ex
pend
iture
Tim
ing:
dai
lyTy
pe:
1. S
tand
ard
pre‐
and
pos
t‐op
ent
eral
fe
edin
g2.Argininesupplementedpre‐opand
post
‐op
ente
ral f
eedi
ng
No
pre‐
op a
nd s
tand
ard
post
‐op
ente
ral
feed
ing
49 m
alno
uris
hed
head
and
ne
ck c
ance
r pat
ient
sM
ean
age
56.6
–61.
6C
omor
bidi
ty fu
lly re
port
ed
6 m
onth
s po
st‐s
urge
ry37
%Be
twee
n ba
selin
e an
d th
e da
y be
fore
sur
gery
, bot
h pr
e‐op
erat
ivel
y fe
d gr
oups
reve
aled
a p
ositi
ve c
hang
e fo
r phy
sica
l and
em
otio
nal
func
tioni
ng a
nd d
yspn
oea
with
sign
ifica
nce
in a
rgin
ine
grou
p. T
his
was
not
sus
tain
ed lo
ng te
rm a
t 6 m
onth
s.•
Supp
lem
ente
d gr
oup
show
ed a
neg
ativ
e ch
ange
in a
ppet
ite
(p =
0.0
49).
Betw
een
base
line
and
6 m
onth
s aft
er s
urge
ry,
• Th
ere
wer
e no
diff
eren
ces b
etw
een
cont
rol a
nd b
oth
pre‐
fed
grou
ps.
Ther
e w
ere
no d
iffer
ence
s in
favo
ur o
f arg
inin
e su
pple
men
t co
mpa
red
to o
ther
feed
gro
up
TAB
LE 2
(C
ontin
ued)
12 of 22 | FAITHFULL eT AL.
TAB
LE 3
O
bser
vatio
nal a
nd q
uasi
‐exp
erim
enta
l pre
habi
litat
ion
stud
ies
with
crit
ical
ana
lysi
s
Refe
renc
e an
d re
sear
ch d
esig
nIn
terv
entio
n an
d co
mpa
rato
rPo
pula
tion
and
sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Baim
a et
al.
(201
5)Fe
asib
ility
stu
dy
with
two
rand
omis
ed (b
y ap
poin
tmen
t tim
e),
non‐
blin
ded
grou
ps
Tim
ing:
1 m
onth
prio
r to
surg
ery.
Type
: in‐
pers
on te
achi
ng o
f ex
erci
ses
plus
info
she
et, p
lus
link
to o
nlin
e vi
deo
prov
ided
Com
para
tor
Vid
eo‐o
nly
teac
hing
arm
60 c
ance
r pat
ient
s un
derg
oing
su
rger
y fo
r bre
ast
canc
er1
mal
e, 5
9 fe
mal
esAge35–81.
(I =
36‐C
24)
Brea
st c
ance
r
3 m
onth
s af
ter
surg
ery
2 w
eeks
to
6 m
onth
s
25%
Exer
cise
com
plia
nce:
• 76
% c
hose
to e
xerc
ise.
• N
o di
ffer
ence
in e
xerc
ise
com
plia
nce
betw
een
in‐p
erso
n te
achi
ng v
ersu
s vi
deo
teac
hing
(OR
= 1.
03).
In p
erso
n 75
% (2
4/32
) com
pare
d to
vid
eo te
achi
ng 7
7% (1
0/13
) Pa
in•
29%
of p
atie
nts
(9/3
1) h
ad w
orse
sho
ulde
r pai
n th
an b
asel
ine
at 1
mon
th
post
‐sur
gery
(24%
, 6/2
5 ex
erci
sers
, and
50%
, 3/6
non
‐exe
rcis
ers)
.•
15%
per
cen
t of p
atie
nts (
4/27
) had
wor
se s
houl
der p
ain
than
bas
elin
e at
3months’post‐surgery(8%,2/23exercisers,and100%,2/2non‐exercisers).
Shou
lder
abd
uctio
n•
66%
of p
atie
nts
(20/
30) l
ost g
reat
er th
an 1
0% s
houl
der a
bduc
tion
ROM
at
1 m
onth
pos
t‐su
rger
y.Pr
ehab
ilita
tion
exer
cise
pro
gram
me
infe
rred
no
addi
tiona
l ris
k of
ser
oma
form
atio
n (E
xerc
iser
s 21
%, 7
/33
vs. n
on‐e
xerc
iser
s 22
%, 2
/9, O
R =
0.94
).N
o st
rong
evi
denc
e of
diff
eren
ceSi
ngle
site
; cha
nge
in in
terv
entio
n ba
sed
on p
atie
nt p
refe
renc
e, s
o no
t ran
dom
; N
o co
ntro
l gro
up: e
very
par
ticip
ant r
ecei
ved
som
e so
rt o
f int
erve
ntio
n; S
tate
d fe
asib
ility
stu
dy, b
ut u
ncle
ar re
: eff
icac
y of
thes
e ho
me
exer
cise
s; N
o
expl
anat
ion
give
n fo
r why
stu
dy s
taff
did
not
pur
sue
mis
sing
dat
a; P
ossi
ble
soci
al d
esira
bilit
y bi
as w
ith “i
n‐pe
rson
” arm
and
thus
impr
oved
com
plia
nce;
C
ompl
ianc
e w
ith e
xerc
ises
sel
f‐re
port
ed, p
ossi
bly
part
icip
ants
ove
rest
imat
ed;
Unc
lear
des
crip
tion
rega
rdin
g se
rom
a fo
rmat
ion/
eval
uatio
n;Ti
me
to fo
llow
‐up
varia
bilit
y (2
wee
ks –
6 m
onth
s); L
umpe
ctom
y an
d m
aste
ctom
y in
clud
ed,
poss
ibly
allo
win
g fo
r ver
y di
ffer
ent o
utco
mes
Jonesetal.(2007)
Sing
le g
roup
des
ign
feas
ibili
ty s
tudy
Freq
uenc
y: fi
ve e
ndur
ance
se
ssio
ns p
er w
eek
on c
onse
cu‐
tive
days
unt
il su
rgic
al
rese
ctio
n.In
tens
ity: h
ighl
y in
divi
dual
ised
an
d pr
ogre
ssiv
e fr
om 6
0%–
100%
VO
2 , P
eak
and
HIIT
se
ssio
ns.
Tim
ing:
car
ried
out f
or
4–6
wee
ks.
Type
: cyc
le e
rgom
etry
Com
para
tor:
Indi
vidu
ally
tailo
red
inte
rven
tion
and
hosp
ital b
ased
ov
er 4
–6 w
eeks
25 p
atie
nts
70%
F
unde
rgoi
ng
surg
ery
for
susp
ecte
d lu
ng
canc
er. M
ean
age
65 ±
10
year
sLu
ng c
ance
r
Pre‐
oper
ativ
e as
sess
men
t30
day
s po
st‐s
urge
ry
Attrition
52%
Adherence
70%
Forpatientswhoachieved≥80%adherence(n
= 1
2), V
O2 p
eak
incr
ease
d 3.
3 m
l kg−1 m
in−1
(p =
0.0
06).
Six‐minutewalktest:Significantimprovementin>80%adherencegroup
(p=0.14)comparedto<80%adherence(p
= 1
.01)
.Th
e ov
eral
l adh
eren
ce ra
te w
as 7
2% (r
ange
, 0%
–100
%) w
ith p
atie
nts
com
plet
ing
a m
ean
of 3
0–27
ses
sion
s (ra
nge,
0–7
5).
No
sign
ifica
nt d
iffer
ence
. (p
> 0.
1) fo
r all
mea
sure
s of
pul
mon
ary
func
tion.
Theaveragedurationofhospitalstaywas10–8dayswith8–5daysingeneral
hosp
ital a
nd 2
–5 d
ays
in th
e in
tens
ive
care
uni
t.N
o di
ffer
ence
in c
ompl
icat
ions
or l
engt
h of
sta
y th
an in
rout
ine
patie
nt c
are.
The
leng
th o
f int
erve
ntio
n m
ay b
e pr
oble
mat
ic in
a 1
to 2
wee
k w
ait t
ime
for
surg
ery,
the
auth
ors
com
men
t on
the
abili
ty to
mak
e si
gnifi
cant
cha
nge
in s
uch
a sh
ort t
ime.
The
re is
no
reco
rdin
g of
how
man
y pa
tient
s di
d no
t mee
t the
el
igib
ility
par
amet
ers
to re
flect
the
norm
al p
ract
ice
(Con
tinue
s)
| 13 of 22FAITHFULL eT AL.
Refe
renc
e an
d re
sear
ch d
esig
nIn
terv
entio
n an
d co
mpa
rato
rPo
pula
tion
and
sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Li e
t al.
(201
3)
Pre–
post
‐inte
rven
‐tio
n st
udy
His
toric
al c
ontr
ol
grou
psi
ngle
‐cen
tre,
co
hort
Freq
uenc
y: In
divi
dual
ised
ae
robi
c ex
erci
se (3
0 m
in ×
3
times
a w
eek,
Inte
nsity
: at 5
0% o
f max
hea
rt
rate
) and
resi
stan
ce tr
aini
ngTi
min
g: th
ree
times
per
wee
k, n
o m
ore
deta
ilTy
pe, o
ne o
r tw
o m
odifi
able
di
etar
y be
havi
ours
iden
tifie
d an
d di
scus
sed,
use
of w
hey
prot
ein
isol
ate
with
in 1
hr o
f ex
erci
se a
t 1.2
g/k
g bo
dy
wei
ght p
er d
ay, 9
0‐m
in v
isit
with
trai
ned
psyc
holo
gist
with
a
focu
s on
anx
iety
redu
ctio
n.
Leng
th o
f pre
habi
litat
ion
dete
rmin
ed b
y w
ait t
ime
for
surg
ery
87patients
unde
rgoi
ng
surg
ery
for
colo
rect
al c
ance
r(C
ontr
ol =
45
inte
rven
tion
= 42
)C
olor
ecta
l can
cer
Assessed1week
pre‐
op, 4
wee
ks
and8weeks
post
‐sur
gery
Prim
ary
outc
ome
mea
sure
6
MW
T @
8weeks
0%Th
e pa
tient
s in
the
preh
abili
tatio
n pr
ogra
mm
e ha
d be
tter
pos
t‐op
erat
ive
wal
king
capacityat8weeks(meandifference,84.5±83m;p<0.01).At8weeks,81%
of th
e pr
ehab
ilita
ted
patie
nts
wer
e re
cove
red
com
pare
d w
ith 4
0% o
f the
co
ntro
l gro
up (p
< 0
.01)
.Th
e pr
ehab
ilita
tion
grou
p al
so re
port
ed h
ighe
r lev
els
of p
hysi
cal a
ctiv
ity b
efor
e an
d af
ter s
urge
ry.
The
post
‐ope
rativ
e co
mpl
icat
ion
rate
s an
d th
e ho
spita
l len
gth
of s
tay
wer
e si
mila
r.Th
ere
wer
e si
gnifi
cant
em
otio
nal a
nd s
ocia
l diff
eren
ces
betw
een
cont
rol a
nd
inte
rven
tion.
The
se a
re n
ot c
ontr
olle
d fo
r in
the
mod
ellin
g or
ana
lysi
s of
di
ffer
ence
. Lac
k of
det
ail r
e‐nu
triti
onal
com
pone
nt. T
he q
uest
ion
of w
hat’s
a
clin
ical
ly re
leva
nt c
hang
e is
not
exp
lore
d.N
O d
ata
on th
e le
ngth
of t
ime
of w
ait f
or s
urge
ry a
nd th
is w
ould
det
erm
ine
the
amou
nt o
f tim
e sp
ent o
n pr
ehab
ilita
tion
inte
rven
tion
(see
col
umn
3). H
isto
rical
co
ntro
l do
not a
ppea
r to
have
had
bas
elin
e as
sess
men
t, ju
st p
re‐o
p an
d 4
and
8week.CouldaccountfordifferencebetweengroupsonHRQoLmeasures,
beca
use
pre‐
op m
easu
res
take
n at
diff
eren
t tim
es (c
ontr
ol ta
ken
imm
edia
tely
be
fore
sur
gery
; int
erve
ntio
n af
ter m
eetin
g w
ith s
urge
on).
No
tool
use
d to
capturefunctionalsymptomsspecifictocolorectalcancer,forexampleFACT‐C,
SF35
is to
o ge
neric
. Com
plia
nce
to p
reha
bilit
atio
n in
terv
entio
n re
port
ed in
di
scus
sion
sec
tion
(70%
exe
rcis
ing
at le
ast 2
day
s pe
r wee
k, 4
5% fu
lly
com
plia
nt).
Incr
ease
in s
elf‐
repo
rted
phy
sica
l act
ivity
per
sist
ed a
fter
sur
gery
Pedd
le e
t al.
(200
9)Su
b‐an
alys
is o
f Jonesetal.(2007)
Freq
uenc
y: fi
ve s
essi
ons
per
wee
k on
con
secu
tive
days
unt
il su
rgic
al re
sect
ion
Inte
nsity
: hig
hly
indi
vidu
alis
ed
and
prog
ress
ive
from
60%
to
100%
VO
2 , P
eak
and
HIIT
se
ssio
ns.
Tim
ing:
4–6
wee
ks p
rior t
o su
rger
y.Ty
pe: e
ndur
ance
cyc
le e
rgom
etry
Com
para
tor i
ndiv
idua
lly ta
ilore
d in
terv
entio
n an
d ho
spita
l bas
ed
over
4–6
wee
ks
19 p
atie
nts
unde
rgoi
ng lu
ng
rese
ctio
n fo
r su
spec
ted
mal
igna
ncy
wer
e pl
anne
d to
co
mpl
ete
base
line
to p
re‐s
urge
ry
inte
rven
tion.
Nin
e pa
tient
s w
ill
full
data
set
Lung
can
cer
QoL
2 m
onth
s po
st‐s
urge
ry
0% S
ubse
t an
alys
isPr
e‐su
rgic
al e
xerc
ise
trai
ning
impr
oved
car
dior
espi
rato
ry fi
tnes
s, it
did
not
see
m
to im
prov
e Q
OL
from
bas
elin
e to
pre
‐sur
gery
or m
itiga
te th
e de
clin
e in
QO
L af
ter s
urge
ry.
QoL
mig
ht b
e in
fluen
ced
by s
ever
al o
ther
fact
ors
for e
xerc
ise
to h
ave
a m
eani
ngfu
l eff
ect.
VO2
Peak
did
impr
ove
TAB
LE 3
(C
ontin
ued)
(Con
tinue
s)
14 of 22 | FAITHFULL eT AL.
Refe
renc
e an
d re
sear
ch d
esig
nIn
terv
entio
n an
d co
mpa
rato
rPo
pula
tion
and
sam
ple
Follo
w‐u
p af
ter
inte
rven
tion
Att
ritio
nCr
itica
l ana
lysi
s
Seki
ne e
t al.
(200
5)Pr
ospe
ctiv
e st
udy
with
usu
al c
are
cont
rol
Freq
uenc
y: 5
× pe
r day
Inte
nsity
: mod
erat
eTi
min
g: 2
wee
ks p
rior t
o su
rger
yTy
pe:
1. In
cent
ive
spiro
met
ry2.Abdominalbreathingand
brea
thin
g ex
erci
ses
3. B
ronc
hodi
lato
rs 5
× pe
r day
4. H
uffin
g an
d co
ughi
ng
exer
cise
s5.
5,0
00 s
teps
per
day
Com
para
tor h
isto
rical
con
trol
gr
oup
of 6
0 pa
tient
s w
ithou
t CO
PD
N=82(con
‐tr
ol=6
0) R
ehab
(n
= 2
2) (r
ehab
gr
oup
had
mor
e ai
rflo
w o
bstr
uc‐
tion
FEV1
/FVC
)22
pat
ient
s w
ith
COPD
.Lu
ng c
ance
r
30 d
ays’
post
‐ope
ratio
n1
mon
th p
ost‐
op
0% Not
re
port
ed
The
chan
ge in
lung
func
tion
as le
ss d
imin
ishe
d in
the
inte
rven
tion
grou
p (p
= 0
.023
)Po
st‐o
pera
tive
pulm
onar
y co
mpl
icat
ions
ther
e w
ere
no d
iffer
ence
sPo
st‐o
pera
tive
hosp
ital s
tays
wer
e si
gnifi
cant
ly lo
nger
in th
e co
ntro
l gro
up
(p=0.003)equivalentto−6.8days
Stud
y do
es n
ot m
athe
mat
ical
ly c
ontr
ol fo
r the
diff
eren
ces
betw
een
grou
ps
re‐b
asel
ine
heal
th. S
tudy
is u
nder
pow
ered
Less
dec
reas
e in
pul
mon
ary
func
tion
(FEV
1 an
d pr
edic
ted
decr
ease
pos
t‐op
) in
reha
b gr
oup
but o
vera
ll pu
lmon
ary
func
tion
was
low
er in
this
gro
up. N
ote:
Thi
s is
pro
babl
y be
caus
e th
is g
roup
had
CO
PD w
here
as th
e co
ntro
ls d
id n
ot.
Post
‐op
stay
was
long
er in
the
cont
rol g
roup
Suep
pel e
t al.
(200
1)D
escr
iptiv
e qu
asi‐e
xper
imen
tal
Freq
uenc
y: d
aily
Inte
nsity
: low
Tim
ing:
sev
eral
wee
ks p
rior a
nd
nigh
t bef
ore
surg
ery
Type
: pel
vic
floor
exe
rcis
es.
Pelv
ic fl
oor m
uscl
e st
reng
then
‐in
g ex
erci
ses
pre‐
op w
ith
biof
eedb
ack
conf
irmat
ion
of
corr
ect p
erfo
rman
ce, t
hen
cont
inue
PM
EsC
ompa
rato
r: PM
Es v
ia v
ideo
, th
en fi
rst b
iofe
edba
ck a
t 6‐
wee
k vi
deo
for p
elvi
c flo
or
mus
cle
exer
cise
s, w
ritte
n in
stru
ctio
ns, n
urse
ver
bal
supp
ort
16 m
en p
re–p
re‐
radi
cal
pros
tate
ctom
yEi
ght m
en p
er
grou
pPr
osta
te c
ance
r
Assessmentat3,
6, 9
, 12
mon
ths
Not
re
port
edAnalysisdescriptivenostatisticalevidence,studyunderpoweredandnot
cont
rolle
d.Po
orly
repo
rted
stu
dy.
Stre
ngth
s: c
onsi
sten
cy o
f bio
feed
back
inst
ruct
ion
by s
ame
nurs
eLi
mita
tions
: mis
sing
dat
a, s
mal
l sam
ple
size
; do
not k
now
prio
r voi
ding
pat
tern
s of
pat
ient
sO
vera
ll so
me
pre‐
op in
form
atio
n w
hile
all
othe
r stu
dies
hav
e be
en d
one
post
‐op
TAB
LE 3
(C
ontin
ued)
| 15 of 22FAITHFULL eT AL.
day) (Sekine et al., 2005) in combination with therapeutic pulmonary exercises in patients with lung cancer prior to surgery. The short timelines prior to therapy made a progressive programme difficult to achieve.Althoughadherencetothehomeexerciseprogrammewasreported in most of these studies, adherence to exercise at the pre‐scribed intensity and progression of the exercise programme were poorly reported.
Only five of the studies provided a nutritional modality as part of the prehabilitation package. Some of the interventions were purely nutrition based (Gillis et al., 2016; Moriya, 2015; Van Bokhorst‐de Van der Schuer et al., 2000); however, two of the studies used nu‐trition as part of multi‐component prehabilitation intervention (Gillis et al., 2016; Li et al., 2013). The nutritional interventions were var‐ied with 5–10 days pre‐operative feeding plus a supplemental argi‐nine formula (Van Bokhorst‐de Van der Schuer et al., 2000) or whey protein (Gillis et al., 2014; Li et al., 2013) or a low or high dose im‐mune‐enhancing diet (Moriya, 2015). Multi‐modal prehabilitation interventions provided 90 min of nutritional counselling with daily whey protein supplementation (Gillis et al., 2016) in comparison with a control group which received nutritional counselling without sup‐plementation. The timing of nutritional interventions varied between 5–10 days (Gillis et al., 2016; Moriya, 2015) and 3–6 weeks pre‐oper‐atively (Gillis et al., 2014; Li et al., 2013). The nutritional intervention did not continue beyond surgery, with one exception (Gillis et al., 2016) which continued the nutritional intervention 4 weeks’ post‐surgery. Nutritional therapies were primarily targeted on individuals with cancer who were malnourished, receiving treatment for head and neck (Van Bokhorst‐de Van der Schuer et al., 2000) or colorectal cancer (Gillis et al., ; Li et al., 2013; Moriya, 2015). Van Bokhorst‐de Van der Schuer et al. (2000) excluded adults from the study if they were well nourished (10% excluded), whereas Gillis et al. (2016) screened for malnutrition using the Patient Generated–Subjective GlobalAssessment(PG‐SGA)whichisavalidatedtoolfornutritionalassessmentinoncology.Adherencetonutritionalinterventionisre‐ported in only one study with researchers contacting participants on a weekly basis to encourage them to record their whey protein ingestion. This study noted that adherence was higher in the preha‐bilitation group compared to the rehabilitation group both pre‐ and post‐surgery.
Studies involving a psychoeducation modality as part of preha‐bilitation programmes have focused primarily on anxiety and stress reduction(Cheville et al., 2015; Garssen et al., 2013; Parker et al., 2009; Schmidt et al., 2015), patient education and lifestyle advice (Baimaetal.,2015;Barlésietal.,2008) (Jensenetal.,2015)and/or counselling (Parker et al., 2009) as part of the intervention; how‐ever, few studies report any detail of the therapeutic components of the intervention. Psychoeducational prehabilitation strategies have been studied as single mode counselling interventions (Barlési et al., 2008;Chevilleetal.,2015)orbycomparingavarietyofpsychologicaland educational approaches prior to cancer treatment (Parker et al., 2009). Psychoeducational strategies have also been studied as part of multi‐component prehabilitation programmes (Gillis et al., 2014; Jensenetal.,).Psychoeducationalinterventionspriortosurgeryfor
lung and gastrointestinal cancer provided written and verbal infor‐mation to participants which described the disease and associated surgeryoutcomes(Barlésietal.,2008;Schmidtetal.,2015).Anal‐ternative psychotherapeutic approach involved weekly group ses‐sions with a psychiatrist, focused on individuals’ social, cognitive and emotional care in conjunction with relaxation exercises 30 days prior to chemotherapy(Cheville et al., 2015). Similarly, Garsen (Garssen et al., 2013) provided 4 sessions over 5 days to women with breast cancer, including stress management, relaxation, guided imagery techniques and counselling. Parker et al. (2009) investigated the ef‐fects of a similar programme on post‐operative recovery outcomes in men with prostate cancer. These interventions were all compared tousualorsupportivecare.Adherencetotheinterventionwasnotalways reported in the observational studies with attrition 25%–52% respectively(Baimaetal.,2015)(Jonesetal.,2007).
3.1 | Objective clinical outcomes following prehabilitation
Studies that included an exercise modality investigated the ef‐fects of prehabilitation regimens on cancer treatment recovery outcomes and cardiopulmonary fitness (Table 4). Three studies reported favourable effects of home‐based pelvic floor training on post‐operative urinary continence outcomes in prostate cancer patients undergoing radical prostatectomy up to 12 months of fol‐low‐up (Burgio et al., 2006; Centemero et al., 2010; Sueppel et al., 2001), and a fourth study (Bales et al., 2000) showed no urinary continence benefits of including biofeedback training. Similarly, a study of female breast cancer patients reported no additional post‐operative benefits when home‐based shoulder exercise prehabili‐tation included an in‐person teaching session versus video‐based instruction (Baima et al., 2015). Supervised exercise prehabilita‐tion programmes in lung cancer patients have generally been more intensive than home‐based programmes and have resulted in im‐provements in pre‐operative cardiopulmonary fitness measures, including six‐minutewalk test (6MWT) (Jones et al., 2007) andpeak VO2(Jonesetal.,2007;Stefanellietal.,2013).However,theimprovements in peak VO2 were modest (2–3 ml kg−1 min−1) and it is unclear whether improvements of this magnitude translate to improved post‐operative recovery outcomes or longer‐term outcomes, such as quality of life. It is of interest to note that in‐tensive cycle ergometry prehabilitation had no impact on qual‐ity of life pre‐surgery or at 2 months post‐surgery (Peddle et al., 2009). Nevertheless, Sekine et al. (2005) reported a reduction in post‐operative pulmonary complications and hospital length of stay in lung cancer patients after a prehabilitation programme that involved daily pulmonary therapeutic exercises and walk‐ing (5,000 steps/day) in the two weeks prior to lobectomy when compared to historical controls. In other studies, prehabilitation programmes involvingexercisehaveyieldedequivocal results.Asupervised programme involving cycling + strengthening exer‐cises in patients with gastrointestinal cancer compared to those in a walking + breathing exercise group showed no differences in
16 of 22 | FAITHFULL eT AL.
TAB
LE 4
Pr
ehab
ilita
tion
RCT
stud
ies
with
sta
tistic
ally
sig
nific
ant o
utco
mes
at 3
0 da
ys p
ost‐t
reat
men
t
Refe
renc
eTu
mou
r ty
pe
Phys
ical
func
tioni
ng
Perc
eive
d ph
ysic
al fu
nctio
nN
utrit
ion
Patie
nt‐r
epor
ted
outc
omes
Serv
ice
bene
fitO
bjec
tive
Gai
t: 6
MW
TV
02
Peak
Grip
St
reng
thFE
V1a
Pad
usag
ea CH
AM
PS
SF36
Ph
ysic
al
func
tion
SF36
Rol
e sc
ales
an
d so
cial
fu
nctio
nBM
I
Self‐
repo
rt
diet
SF36
m
enta
l co
mpo
‐ne
ntPa
in
scor
esa
HA
Ds
STA
IPO
Ms
FAC
T‐La
ICS
mal
e SF
a LO
S
Less
ho
spita
l‐is
atio
n
Few
er
com
pli‐
catio
ns
Bal
es e
t al.
(200
0)Pr
osta
te
canc
er
N
S
Bar
lési
et a
l. (2008)
NSC
LC
Bur
gio
et a
l. (2
006)
Pros
tate
ca
ncer
+ve
Car
li et
al.
(201
0)C
olor
ecta
l ca
ncer
NS
NS
Cen
tem
ero
et a
l. (2
010)
Pros
tate
ca
ncer
+ve
+v
e
Che
ville
et a
l. (2
015)
GI a
nd g
all
blad
der
+ve
Gar
ssen
et a
l. (2
013)
Bre
ast
canc
er
NS
+ve
Gill
is e
t al.
(201
4)C
olor
ecta
l ca
ncer
+ve
N
S
N
SN
SN
S
Gill
is e
t al.
(201
6)C
olor
ecta
l ca
ncer
NS
N
S
N
SN
S
NS
Jensenetal.
(201
4)B
ladd
er
canc
er
Jensenetal.
(201
5)B
ladd
er
canc
er
NS
N
S
Mor
iya
(201
5)C
olor
ecta
l ca
ncer
N
S
+ve
Park
er e
t al.
(200
9)Pr
osta
te
canc
er
+v
e
NS
Schm
idt e
t al.
(201
5)G
I,GU
and
th
orac
ic
canc
ers
+v
e
NS
N
S
Stef
anel
li et
al.
(201
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| 17 of 22FAITHFULL eT AL.
6 MWT distance (Carli et al., 2010). Similarly, home‐based exercise programmes involving aerobic and/or resistance exercise 4 weeks prior to surgery have had minimal impact on post‐operative hos‐pital length of stay or severity of complication (Gillis et al., 2014; Jensenetal., ), although Jensenetal. (2015) reported improvedpost‐operative 6 MWT distance in bladder cancer patients receiv‐ingprehabilitation,4,806m(95%CI4,075–5,536m)comparedto2,906m (95%CI 2,408–3,404m) in those receiving usual care.Gillis (Gillis et al., 2014) reported higher submaximal cardiopulmo‐nary fitness +23.4 m (6 MWT) in a prehabilitation/rehabilitation groupcomparedtorehabilitationalone−21.8m(80.7)at8weeksafter colorectal cancer surgery.
Studies that included nutritional outcomes were few and re‐ported no significant differences between the intervention and control groups at ≥30days (Moriya, 2015) on post‐treatmentphysical functioning (Table 4). However, pre‐operative nutritional modality groups showed a significant improvement in physical functioning and initial symptoms post‐operatively (Gillis et al., 2014; Li et al., 2013; Van Bokhorst‐de Van der Schuer et al., 2000). Only one study measured upper‐body strength (Gillis et al., 2016), and this improved pre‐surgery but was not sustained post‐surgery. Participants who received arginine supplementation with feeding pre‐ and post‐surgery showed reduced appetite at 6 months (Van Bokhorst‐de Van der Schuer et al., 2000), and serum albumin re‐mained stable in a small (n = 17) pre–post‐intervention study (Li et al., 2013). However, prehabilitation studies’ nutritional outcomes are compromised by the lack of consistency in measuring nutritional intake and adherence (mainly through self‐report tools) or objec‐tive sarcopenia measures. Such limitations could have important
implications for assessing treatment fidelity and the sensitivity of outcome measures.
3.2 | Patient‐reported outcomes (PRO) of prehabilitation
PRO in the studies reviewed included health‐related quality of life using the Short Form Health Survey (SF36) and Prostate Cancer Index (PCI), which incorporate physical and emotional subscales. Symptom specific measures such as the International Continence Scaleformen(ICSmale),theHospitalAnxietyandDepressionScale(HADs)and(PCI)andActivitiesofDailyLiving(ADL)toolwerealsoreported in some studies (Table 4). Quality of life scores were com‐parable between prehabilitation and control groups at 3 months post‐interventioninmoststudies(Barlésietal.,2008;Burgioetal.,2006; Garssen et al., 2013; Peddle et al., 2009). However, in two studies, self‐reported physical function was higher in the prehabili‐tation group at 1 year (Li et al., 2013; Parker et al., 2009), and in the study by Li et al. (2013), an increase in self‐reported physical activity persisted 8weeks after surgery. Post‐treatment improve‐ments in mood, anxiety and depression have been reported imme‐diately post‐operatively following prehabilitation involving walking + breathing exercises and psychological support (Carli et al., 2010; Parker et al., 2009; Schmidt et al., 2015) but effects were small and between‐group differences were not sustained long‐term (Parker et al., 2009; Schmidt et al., 2015). Behavioural change techniques, such as smoking cessation, were rarely reported in studies; this can impact on radiotherapy side effects and subsequent post‐treatment cancer outcomes (Warren, Sobus, & Gritz, 2014).
F I G U R E 2 Summary of multi‐modality prehabilitation outcomes and measurement
PREHABILITATION INTERVENTIONExercisemodality• Cardio-pulmonary exercise• Walking• Flexibility exercise• Balance• Strengthexercises• Targetedexercise e.g. Breathing exercises, pelvic floor
exercises
Nutrition modality• Supplementa�on• Personalisednutri�onal counselling e.g.weight loss• Increase protein intake• Alcohol reduc�on advice
Psychosocial and education modality• Anxiety reduc�on• Cogni�ve behavioural therapy (CBT)• Enhancing self-efficacy (ACT)• Smoking cessa�on• Pa�ent ac�va�on and behavioural change coaching
PHYSICAL FUNCTIONMEASURESObjec�vemobility• CPET V02 Peak• Gait: 6 MinuteWalk Test• Chair rise: Sit to stand• Grip strength• Timed up and go
PATIENT REPORTEDOUTCOMES• QOL• Hospital Anxiety and Depression
HADs• SF36 physical func�on• Ac�vi�es ofDaily Living)
NUTRITIONALMEASURES• BMI• Hip to waist ra�o• Serum Albumin• Sarcopeniameasures• Self report diet diary
PATIENT BENEFIT• Reduced disability• Independence• Reduced
complica�ons andadverse events
• Reduced lengthofhospitalisa�on
• Reduced number offalls
• Return to work• Enhanced ac�vi�es
of daily living
Risk factors forPOORER CANCERTREATMENTOUTCOME
• Obesity• Presence of
comorbidity• Older age• Func�onal
impairment• Mul�ple symptoms
PROCESS measures of PrehabilitationPar�cipa�on from popula�on and adherenceFrequency, intensity, �ming and typeof prehabilita�on interven�onSafety considera�ons (e.g. restric�ons, adverse events)
Examplesof dimensionmeasures
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3.3 | Patient‐reported and service outcomes for prehabilitation
Complication rates and length of hospital stay (LOS) post‐sur‐gery were the most frequent service delivery measures reported for≥30dayspost‐treatment (Table4). Therewasnodifference inlength of stay, between prehabilitation and control groups in five studies(Gillisetal.,;Jensenetal.,2014;Lietal.,2013;Schmidtetal., 2015), with the exception of Sekines (Sekine et al., 2005), where the intervention group had a reduced length of stay after a 4‐ to 6‐week prehabilitation programme. Post‐operative complications such as wound healing, seroma formation and bleeding were shown to be comparable between intervention and control groups but Moriya (Moriya, 2015) found that those receiving a prehabilitation nutritional intervention had fewer post‐operative site infections. Prehabilitation has been shown to improve initial post‐operative mobilisation(Jensenetal.,2015)andthenumberofpatientscom‐pleting chemotherapy (Cheville et al., 2015). Furthermore, in the lat‐ter study, those receiving the intervention had significantly fewer treatment hospitalisations.
4 | DISCUSSION
Overall, this systematic review suggests prehabilitation impacts on select 30‐day outcome measures for some people with cancer but few studies have measured or reported overall long‐term health benefits. The results of the review are summarised pictorially as a diagram describing the multi‐modality intervention and linked physi‐cal function, nutrition and patient‐reported outcomes used in the reviewed studies (Figure 2). Many of these studies report service or process data measures such as length of stay and post‐operative complications, but do not consistently capture changes in physical functioning or patient‐reported outcomes. The only exception is pre‐operative therapeutic pelvic floor exercises for men undergoing prostatectomy for prostate cancer where prehabilitation improved long‐term urinary continence. This reflects the differentiation be‐tween general prehabilitation versus targeted exercise or nutrition interventions and the greater specificity of their effect. There is in‐sufficient evidence for demonstration of long‐term benefits in other cancer patient populations beyond the initial 30 days post‐treat‐ment complications. Even vigorous intensity pre‐operative aerobic exercise conditioning programmes have only resulted in modest improvements in peak oxygen uptake pre‐operatively (of the order of 2–3 ml kg−1 min−1), possibly a factor of the short duration of pro‐grammes, and these gains are lost post‐operatively. Not surprisingly then, prehabilitation combined with rehabilitation was the most ef‐fective approach in improving outcomes longer than 30 days.
It is now recognised that a physically active lifestyle is in‐versely related to the risk of certain cancers and mortality (Brown, Winters‐Stone, Lee, & Schmitz, 2012; Schmid & Leitzmann, 2014). Surprisingly few prehabilitation studies measured or re‐ported participant comorbidities and how they changed over
time. Therefore, we were unable to address our second question, how prehabilitation can optimise the management of cancer pa‐tients with comorbidity? Comorbidities in participants in preha‐bilitation studies were considered exclusion criteria rather than as predictors of physical functioning that could be mediated by exercise or nutrition and that could change as a response to inter‐vention (Brown et al., 2012). Those participants with high levels of comorbidities and poor fitness were often not eligible to be included, which suggests those people most in need to improve physical function were less likely to receive prehabilitation. The multi‐modality approach of prehabilitation could optimise the management of cancer patients with low baseline scores and who have been shown to gain greater benefits (Minnella et al., 2016). Rather than trying to demonstrate the efficacy of multi‐modality prehabilitation on the fittest patients, we should consider using the approach to optimise the management of the more complex and least fit cancer patients who have most to gain. This requires more sophisticated tailoring of intervention to personalise and target prehabilitation. For example, current exercise guidelines for cancer survivors recommend muscle strengthening exercises for overall conditioning (Schmitz et al., 2010) but this may not be sufficient to manage specific deficits. A more task‐specific ap‐proach incorporating functional movements using strength and mobility may be optimal for prehabilitation regimens (Winters‐Stone et al., 2015).
In some studies, the high attrition of participants suggests a bal‐ance is required between intensity and duration of exercise to be able to meet the needs of those with greater limitations. This highlights the need for continuity and support in establishing exercise habits and expectations around exercise for people with cancer (Brown et al., 2012; Mayo et al., 2011). The content of exercise programmes is poorly described in some papers and has not followed the FITT principle of reporting Frequency, Intensity, Timing and Type of ex‐ercise and/or how the exercise programme is personalised or pro‐gressed over time (Thompson, Gordon, & Pescatello, 2010). These oversights make it challenging to understand whether or not the ex‐ercise programme was insufficiently designed and/or how to revise programmes to optimise adherence and outcomes in the future.
The inclusion of nutritional support as part of prehabilitation improved short‐term physical function. The pre‐surgical interven‐tions were necessarily short (2–3 weeks) primarily due to treatment target times. Indications from one study suggest that longer‐term patient outcomes could benefit with additional post‐surgical reha‐bilitation. Given the rising proportion of cancer patients who are obese at diagnosis, the prehabilitive window and rehabilitative window are potentially an opportunity to embed new lifestyle behaviours. Malnutrition is associated with a poorer response to cancer treatment, and hypoalbuminaemia is associated with post‐surgical mortality, increased morbidity and length of stay (Hu et al., 2015). Patients with colorectal cancer are more malnourished thanotherpatientsgroups(28%colorectalcomparedto4%pros‐tate cancer) (Hu et al., 2015) hence the wide number of prehabil‐itation studies in this population. In the nutrition components of
| 19 of 22FAITHFULL eT AL.
prehabilitation programmes, surrogate measures were used for the combined interventions rather than specific targets such as serum values or anthropometric measures. If we are tackling obesity in cancer and its risks, then a greater focus on adiposity, fat distri‐bution and sarcopenia should be included in prehabilitation stud‐ies. With emerging therapies and earlier diagnosis techniques, for example of low dose computerised imaging in lung cancer (Smith, Khanna, & Wisotzky, 2017), the opportunity for prehabilitation be‐comes more feasible as patients are less likely to be burdened by advanced disease or chronic illness.
Understanding how prehabilitation components work together is a challenge as few studies used a theoretical or conceptual frame‐works to guide design. Exploring how the multi‐modality components work, such as exercise, nutrition, psychoeducational components, is essential to maximise outcomes (Figure 2). The use of factorial re‐search designs in future studies is recommended in evaluating pre‐habilitation components (Montgomery, Peters, & Little, 2003). While pre‐operative exercise programmes have incorporated both aerobic and resistance training, most emphasis has been on aerobic exercise. The effect of resistance exercise on pre‐operative muscular function and how this impacts upon post‐operative recovery outcomes has received less attention (Singh et al., 2013). The relationship between psychological health and exercise behaviour has been well estab‐lished. Short‐ and long‐term adherence may be optimised if anxiety and depression are also addressed during an exercise programme; however, the focus on anxiety and depression management at the expense of evidence‐based behaviour change strategies may not be thebeststrategyforlong‐termadherence(Stacey,James,Chapman,Courneya, & Lubans, 2015).
Alimitationofthisreviewisthatconclusionshavetobecon‐sidered in the context of a limited number of studies, the majority of which are underpowered feasibility studies. The importance of feasibility studies is recognised in the Medical Research Council (MRC) complex intervention framework and that they should now be used to inform fully powered RCTs. The review highlighted the need for improved quality of studies, for example following con‐sort or strobe reporting guidance, and this has also been described in previous prehabilitation systematic reviews (Singh et al., 2013). It is imperative that future studies take a more ambitious approach to test efficacy by building on the current evidence base using a conceptual framework to guide intervention design and robust evaluation.
Can prehabilitation programmes impact on longer‐term cancer health outcomes? The answer is currently unclear especially in rela‐tion to changing comorbidity. Prehabilitation is now an integral part of many cancer surgical preparatory pathways as part of early recov‐ery but there is scope for greater targeting to include nutrition and psychoeducational components, as well as considering how prehabil‐itative interventions may buffer symptoms such as fatigue and pain during adjuvant therapies. Sophisticated research designs incorpo‐rating economic evaluation and longer‐term measures are essential to guide service development and support implementation if the concept of cancer prehabilitation is to emulate cardiac rehabilitation services.
In conclusion, prehabilitation strategies may have an important role to play in addressing the rising complexity of health needs of those diagnosed with cancer. Forty per cent of all those diagnosed with cancer have one comorbid condition and 15% at least two con‐current health problems (Sarfati et al., 2016). This systematic review highlights that single‐ and multi‐modal prehabilitation programmes are feasible and some approaches confer short‐term benefits in the post‐surgical recovery period. The next stage is to design robust efficacy studies to test carefully defined prehabilitative/prehabilita‐tive–rehabilitative interventions at the time of first cancer treatment (be that surgery, systemic anti‐cancer therapy or radiotherapy) and measure clinical outcome, PRO, patient benefit and service delivery outcomes throughout the care pathway.
CONFLIC TS OF INTERE S T
The authors have no conflicts of interest to report.
AUTHORS CONTRIBUTION
Allauthorshavemadeasubstantivecontributiontothepublication:S Faithfull, L Turner and K Poole developed the protocol and con‐tributed to the review, analysis andwriting. RManders, JWeprinandMJoycontributed to theanalysis andKWinters‐Stoneand JSaxtonassistedwithdraftingthepublication.Allauthorsapprovedthe final version.
ORCID
Sara Faithfull https://orcid.org/0000‐0002‐7951‐0243
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How to cite this article: Faithfull S, Turner L, Poole K, et al. Prehabilitationforadultsdiagnosedwithcancer:Asystematic review of long‐term physical function, nutrition and patient‐reported outcomes. Eur J Cancer Care. 2019;e13023. https://doi.org/10.1111/ecc.13023