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EUO
Collaborative
Review
–
Prostate
Cancer
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-analysis
Giovanni
E.
Cacciamani
a,
*,
Marissa
Maas
a
,
Nima
Nassiri
a
,
David
Ortega
a
,
Karanvir
Gill
a
,
Paolo
Dell’Oglio
b
,
George
N.
Thalmann
c
,
Axel
Heidenreich
d
,
James
A.
Eastham
e
,
Christopher
P.
Evans
f,g
,
R.
Jeffrey
Karnes
h
,
Andre
L.
De
Castro
Abreu
a
,
Alberto
Briganti
i
,
Walter
Artibani
j
,
Inderbir
Gill
a
,
Francesco
Montorsi
i
a
The
Catherine
and
Joseph
Aresty
Department
of
Urology,
USC
Institute
of
Urology,
Keck
School
of
Medicine,
University
of
Southern
California,
Los
Angeles,
CA,
USA;
b
Niguarda
Hospital,
Urology,
Milan,
Italy;
c
Department
of
BioMedical
Research,
Urology
Research
Laboratory,
University
of
Bern,
Bern,
Switzerland;
d
Department
of
Urology,
Uro-Oncology,
Robot
Assisted
and
Reconstructive
Urologic
Surgery,
University
Hospital
Cologne,
Cologne,
Germany;
e
Urology
Service,
Department
of
Surgery,
Memorial
Sloan
Kettering
Cancer
Center,
New
York,
NY,
USA;
f
Department
of
Urologic
Surgery,
University
of
California,
Davis,
CA,
USA;
g
UC
Davis
Comprehensive
Cancer
Center,
Sacramento,
CA,
USA;
h
Department
of
Urology,
Mayo
Clinic,
Rochester,
MN,
USA;
i
Department
of
Urology
and
Division
of
Experimental
Oncology,
Urological
Research
Institute
(URI),
IRCCS
San
Raffaele
Scientific
Institute,
Milan,
Italy;
j
Urologic
Clinic,
Department
of
Oncological
and
Surgical
Sciences,
AOU
Integrata
and
University
of
Verona,
Verona,
Italy
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
ava
ilable
at
www.sciencedirect.com
journa
l
homepage:
euoncology.europeanurology
.com
Article
info
Article
history:
Received
18
September
2020
Received
in
revised
form
22
January
2021
Accepted
February
12,
2021
Associate
Editor:
Gianluca
Giannarini
Keywords:
Radical
prostatectomy
Prostate
cancer
Pelvic
lymphadenectomy
Pelvic
lymph
node
dissection
Extended
pelvic
lymph
node
dissection
Complications
Abstract
Context:
Pelvic
lymph
node
dissection
(PLND)
yields
the
most
accurate
staging
in
patients
undergoing
radical
prostatectomy
(RP)
for
prostate
cancer
(PCa),
although
it
can
be
associated
with
morbidity.
Objective:
To
systematically
evaluate
the
impact
of
PLND
extent
on
perioperative
morbidity
in
patients
undergoing
RP.
A
new
PLND-related
complication
assessment
tool
is
proposed.
Evidence
acquisition:
A
systematic
review
according
to
the
Preferred
Reporting
Items
for
Systematic
Reviews
and
Meta-analyses
(PRISMA)
was
conducted.
MED-
LINE/PubMed,
Scopus,
Embase
and
Web
of
Science
databases
were
searched
to
yield
studies
discussing
perioperative
complications
following
RP
and
PLND.
The
extent
of
PLND
was
classified
according
to
the
European
Association
of
Urology
PCa
guidelines.
Studies
were
categorized
according
to
the
extent
of
PLND.
Intra-
and
postoperative
complications
were
classified
as
“strongly,”
“likely,”
or
“unlikely”
related
to
PLND.
Anatomical
site
of
perioperative
complications
was
recorded.
A
cumulative
meta-analysis
of
comparative
studies
was
conducted
using
Review
Manager
5.3
(Cochrane
Collaboration,
Oxford,
UK).
Evidence
synthesis:
Our
search
generated
3645
papers,
with
176
studies
meeting
the
inclusion
criteria.
Details
of
77
303
patients
were
analyzed.
Of
these
studies,
84
*
Corresponding
author.
USC
Urology
Institute
of
Urology,
Keck
School
of
Medicine,
University
of
Southern
California,
1516
San
Pablo
St,
90033
Los
Angeles,
CA,
USA.
Tel.
+1
626
491
1531.
E-mail
address:
giovanni.cacciamani@med.usc.edu
(G.E.
Cacciamani).
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
https://doi.org/10.1016/j.euo.2021.02.001
2588-9311/©
2021
European
Association
of
Urology.
Published
by
Elsevier
B.V.
All
rights
reserved.
1.
Introduction
The
current
European
Association
of
Urology
(EAU)
prostate
cancer
(PCa)
guidelines,
recommends
performing
extended
pelvic
lymph
node
dissection
(ePLND)
in
patients
undergo-
ing
radical
prostatectomy
(RP)
when
the
risk
of
lymph
node
metastases
exceeds
5%
[1].
Pelvic
lymph
node
dissection
(PLND)
offers
the
optimal
approach
for
the
identification
of
metastases
and
accurate
staging
[1]
in
the
management
of
clinically
localized
PCa.
However,
the
therapeutic
role
of
PLND
during
RP
is
still
controversial
[2–4].
Conventional
radiologic
imaging
techniques
are
insufficient
to
detect
lymph
node
metastases
reliably.
More
recently,
prostate-
specific
membrane
antigen
positron
emission
tomography
(PSMA-PET)
imaging
has
shown
promise
in
identifying
lymph
node
metastases
[5],
but
data
regarding
the
ability
of
PSMA-PET
to
potentially
exclude
men
from
PLND
are
lacking.
The
technical
challenges
and
potential
complications
of
PLND,
especially
ePLND,
warrant
careful
consideration
when
recommending
the
procedure
[6].
A
comparison
of
PLND
templates
at
experienced
centers
suggested
a
considerable
increase
in
the
overall
complication
rate
[7,8]
and
the
length
of
hospitalization
with
ePLND
[7].
Nonetheless,
the
impact
of
PLND
extent
on
periopera-
tive
morbidity
showed
conflicting
findings.
The
aim
of
this
study
is
to
systematically
evaluate
the
complications
associated
with
PLND
in
patients
undergoing
RP
for
PCa,
in
order
to
answer
four
key
questions
(KQs):
KQ1:
What
is
the
impact
of
PLND
with
regard
to
perioperative
morbidity
in
patients
undergoing
RP
and
PLND?
KQ2:
How
is
perioperative
morbidity
reported,
and
what
is
the
impact
of
EAU
Ad
Hoc
Panel
recommendations
on
perioperative
complication
reporting
[9]?
KQ3:
What
is
the
impact
of
PLND
extent
on
perioperative
morbidity?
KQ4:
Are
there
predictors
of
complications
in
patients
undergoing
RP?
2.
Evidence
acquisition
2.1.
Study
design
Figure
1
depicts
the
workflow
of
the
present
study.
Briefly,
we
performed
a
systematic
review
of
the
literature
to
identify
all
available
clinical
prospective
randomized
and
nonrandomized
trials
and
retrospective
comparative
and
noncomparative
studies
reporting
morbidity
following
RP
and
PLND.
The
articles
retrieved
were
categorized
according
to
the
extent
of
PLND
defined
by
the
published
EAU-ESTRO-
ESUR-SIOG
guidelines
on
PCa
[1].
Subsequently,
we
performed
a
critical
evaluation
of
complications
reported
in
the
studies
retrieved
from
the
literature
review
according
to
the
EAU
Ad
Hoc
Panel
on
complication
reporting
[9].
From
the
analytic
perspective,
we
first
performed
a
pooled
analysis
to
explore
the
type
of
complications
that
are
primarily
related
to
PLND.
After
an
internal
discussion
among
the
authors,
we
were
able
to
define
intraoperative
[10]
and
postoperative
[9]
complications
that
are
“strongly,”
“likely,”
and
“unlikely”
related
to
PLND
(see
below
for
definition).
Following
this,
to
assess
the
impact
of
PLND
extent
on
perioperative
complications,
we
performed
an
intervention
meta-analysis
of
studies
comparing
standard/
limited
PLND
(sPLND/lPLND)
versus
ePLND/superextended
PLND
(sePLND)
and
an
inverse
variance
meta-analysis
of
(47.7%),
combining
data
on
28
428
patients,
described
intraoperative
complications
as
an
outcome
of
interest.
Overall,
534
(1.8%)
patients
reported
one
or
more
intraoperative
complications.
Postoperative
complications
were
reported
in
151
(85.7%)
studies,
combining
data
on
73
629
patients.
Overall,
10
401
(14.1%)
patients
reported
one
or
more
postoperative
complication.
The
most
reported
postoperative
complication
strongly
related
to
PLND
was
lymphocele
(90.6%).
The
pooled
meta-
analysis
revealed
that
RP
+
limited
PLND/standard
PLND
had
a
significantly
de-
creased
risk
of
experiencing
any
intraoperative
complication
(risk
ratio
[RR]:
0.55;
p
=
0.01)
and
postoperative
complication
strongly
related
to
PLND
(RR:
0.46;
p
=
<0.00001),
particularly
for
lymphocele
formation
(RR:
0.52;
p
=
0.0003)
and
thromboembolic
events
(RR:
0.59;
p
=
0.008),
when
compared
with
extended/
superextended
PLND.
The
extent
of
PLND
was
confirmed
to
be
an
independent
predictor
of
lymphocele
formation
(RR:
1.77;
p
<
0.00001).
Conclusions:
The
perioperative
morbidity
of
PLND
in
patients
undergoing
RP
and
PLND
for
PCa
significantly
correlates
with
the
extent
of
PLND.
More
standardized
reporting
of
intra-
and
postoperative
complications
is
needed
to
better
estimate
the
direct
impact
of
PLND
extent
on
perioperative
morbidity.
Patient
summary:
Pelvic
lymph
node
dissection
(PLND)
is
the
most
accurate
method
for
staging
in
patients
undergoing
radical
prostatectomy
for
prostate
cancer,
although
it
can
be
associated
with
complications.
This
study
aims
to
systematically
evaluate
the
impact
of
PLND
extent
on
perioperative
complications
in
these
patients.
We
found
that
intra-
and
postoperative
complications
correlate
significantly
with
the
extent
of
PLND.
A
more
rigorous
assessment
and
thorough
reporting
of
perioperative
complications
are
recommended.
©
2021
European
Association
of
Urology.
Published
by
Elsevier
B.V.
All
rights
reserved.
Morbidity
Lymphocele
Thromboembolic
events
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
2
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
predictors
for
perioperative
morbidity
related
to
PLND
(see
below
for
definition).
Ultimately,
recommendations
were
developed
for
reporting
of
complications
in
patients
undergoing
RP
and
PLND
for
PCa.
2.2.
Definitions
of
PLND-related
complications
It
is
challenging
to
discern
whether
a
perioperative
complication
is
connected
to
RP
or
PLND.
We
believe
that
a
standardized
definition
should
be
provided
to
better
classify
morbidity
of
patients
undergoing
RP
and
PLND
for
PCa:
1
Complication
strongly
related
to
PLND:
any
perioperative
complication
directly
associated
with
the
violation
of
the
lymphatic
system,
not
explainable
otherwise
(ie,
symp-
tomatic
lymphoceles
or
vascular
injury
to
the
iliac
vessels).
2
Complication
likely
related
to
PLND:
any
perioperative
complication
that
is
likely,
but
not
exclusively,
associated
with
the
violation
of
the
lymphatic
system
that
has
been
reported
even
in
the
absence
of
PLND
(ie,
venous
thrombosis).
3Complication
unlikely
related
to
PLND:
any
perioperative
complication
that
cannot
be
directly
or
indirectly
associated
with
the
violation
of
the
lymphatic
system
(ie,
rectal
injury).
2.3.
Search
strategy
for
relevant
studies
A
systematic
search
of
original
articles
published
up
to
March
2020
was
performed
according
to
the
Preferred
Reporting
Items
for
Systematic
Reviews
and
Meta-analyses
(PRISMA)
statement
[11].
The
present
study
is
registered
in
PROSPERO
(registration
number
CRD42020192048).
PubMed/MEDLINE,
Scopus,
Embase
and
Web
of
Science
databases
were
screened
for
observational
comparative
and
noncomparative
studies
on
“radical
prostatectomy
AND
pelvic
lymph
node
dissection”
for
the
treatment
of
localized
PCa
reporting
the
following
outcomes
of
interest:
overall
intraoperative
complications;
overall,
minor
(Clavien
I–II),
and
major
(Clavien
III–V)
complications;
postoperative
sequelae
(>90
d);
and
readmissions.
All
articles
were
distinguished
according
to
the
level
of
evidence
(LOE)
for
therapeutic
studies.
Only
studies
that
reported
perioperative
outcomes
after
RP
and
PLND,
Fig.
1
–
Study
design.
Description
of
each
step
is
provided
as
follows:
(1)
all
available
clinical
prospective
randomized
and
nonrandomized
trials
and
retrospective
comparative
and
noncomparative
studies
reporting
morbidity
after
RP
and
PLND;
(2)
classification
of
studies
according
to
the
PLND
extent
defined
as
reported
by
the
EAU-ESTRO-ESUR-SIOG
guidelines
on
PCa;
(3)
critical
evaluation
of
complication
reporting
of
the
studies
retrieved
from
the
literature
review
according
to
the
EAU
Ad
Hoc
Panel
on
complication
reporting;
(4)
pooled
analysis
to
explore
the
type
of
intra-
and
postoperative
complications
that
are
related
mainly
to
PLND;
(5)
internal
audit
among
authors
to
define
perioperative
complications
that
are
“strongly,”
“likely,”
and
“unlikely”
related
to
PLND;
(6)
pooled
sensitivity
analysis
to
explore
the
types
of
intra-
and
postoperative
complications
that
are
related
mainly
to
PLND;
(7)
pooled
analysis
to
explore
the
impact
of
PLND
extent
on
intra-
a7nd
postoperative
complications;
(8)
pooled
analysis
to
explore
the
predictors
of
intra-
and
postoperative
complications
that
are
related
mainly
to
PLND;
and
(9)
recommendations
on
perioperative
complication
reporting
in
patients
undergoing
RP
and
PLND
for
PCa.
EAU
=
European
Association
of
Urology;
PCa
=
prostate
cancer;
PLND
=
pelvic
lymph
node
dissection;
RP
=
radical
prostatectomy.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
3
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
defined
as
having
at
least
one
of
the
EAU
complication
reporting
criteria
(with
the
exception
of
“method
of
accruing
data
defined”
or
“duration
of
follow-up
indicated”
criteria)
[9],
were
included
in
the
analysis
(Fig.
1).
We
excluded
reviews,
meta-analyses,
papers
on
surgical
technique
description
without
data
of
interest,
as
well
as
replies,
commentaries,
letters
to
the
editor,
editorial
comments,
single
case
reports,
nonmatching
articles,
and
studies
not
providing
outcomes
of
interest.
We
excluded
studies
analyzing
national
databases
because
of
the
high
risk
of
overlapping
data.
The
Population,
Intervention,
Comparators,
Outcomes,
Timing,
and
Setting
(PICOTS)
format
fully
summarizes
our
research
and
analysis
strategy
for
evaluating
the
outcomes
of
interest
(PROSPERO
CRD42020192048).
2.4.
Definition
of
the
extent
of
PLND
The
extent
of
PLND
was
categorized
as
follows:
(1)
no
PLND;
(2)
lPLND:
obturator
nodes;
(3)
sPLND:
obturator
and
external
iliac
nodes;
(4)
ePLND:
obturator,
external,
and
internal
iliac
nodes;
(5)
sePLND:
ePLND
plus
common
iliac,
presacral,
and/or
other
nodes;
(6)
the
extent
of
PLND
undefined
or
unclassified;
and
(7)
salvage
PLND
(salPLND)
[1].
Studies
reporting
discrepant
definitions
were
reclassi-
fied
according
to
the
above
definitions.
Variants
in
the
extent
of
PLND
have
been
recorded.
2.5.
Screening
and
data
extraction
Two
paired
investigators
(M.M.
and
D.O.)
screened
all
articles
independently,
focusing
the
research
on
papers
reporting
any
of
the
outcomes
of
interest.
Any
disagreement
about
eligibility
was
resolved
by
discussion
with
a
senior
(G.
E.C.)
author
until
a
consensus
was
reached.
2.6.
Statistical
analysis
Several
types
of
analyses
have
been
performed
where
necessary,
which
are
described
as
follows.
2.6.1.
Cumulative
analysis
of
each
type
of
complication
Quantitative
data
have
been
summarized
and
presented
in
tables
and
charts
where
necessary.
The
data
retrieved
from
this
review
are
presented
as
number
of
events
(complica-
tions)
or/and
number
of
patients
as
appropriate.
Note
that
we
carried
out
a
preliminary
screening
of
the
literature.
We
found
heterogeneity
in
the
outcome
reporting.
For
example,
in
some
studies,
the
number
of
complications
is
equal
to
the
number
of
patients
who
have
reported
a
complication.
In
some
other
studies,
the
number
of
complications
is
higher
than
the
number
of
patients
who
have
reported
complica-
tions
(evidence
that
some
patients
experienced
more
than
one
complication).
As
such,
since
we
cannot
assume
that
the
number
of
complications
reported
is
“per
level,”
the
percentages
reported
refer
to
the
number
of
events
out
of
the
number
of
complications
in
each
complication
category
as
appropriate.
2.6.2.
Quality
of
complication
reporting
Quality
of
reporting
and
grading
complications
was
assessed
according
to
the
EAU
Ad
Hoc
Panel
recommenda-
tions
[9].
To
establish
a
possible
change
of
attitude
toward
the
reporting
of
complications,
temporal
and
spatial
(location-based)
comparisons
were
performed,
evaluating
reporting
patterns
before
versus
after
the
introduction
of
the
EAU
guideline
on
complication
reporting
in
2012
[9].
Data
for
categorical
variables
are
shown
as
percentages,
and
differences
between
groups
were
analyzed
with
Pearson’s
chi-square
test
or
Fisher’s
exact
test,
as
appropri-
ate.
All
statistical
analyses
were
performed
using
IBM
SPSS
Statistics
24.0
(IBM
Corp.,
College
Station,
TX,
USA).
2.6.3.
Intervention
meta-analysis/pooled
analysis
for
lPLND/sPLND
versus
ePLND
and
no
PLND
versus
any
PLND
When
reported,
data
have
been
analyzed
according
to
any
surgical
approach
(open,
laparoscopic,
or
robotic)
and
cumulatively.
Statistical
heterogeneity
was
tested
using
the
chi-square
test.
A
p
value
<0.10
will
be
used
to
indicate
heterogeneity.
In
case
of
a
lack
of
heterogeneity,
fixed-effect
models
were
used
for
the
pooled/meta-analytic
analysis.
Random-effect
models
were
used
in
case
of
heterogeneity.
The
results
were
expressed
as
weighted
mean
differences
and
standard
deviations
or
continuous
outcomes
and
as
risk
ratios
(RRs)
and
95%
confidence
intervals
(CIs)
for
dichoto-
mous
variables,
as
appropriate
[12].
2.6.4.
Inverse
variance
meta-analysis/pooled
analysis
All
Cox
regression
and
logistic
regression
analyses
were
recorded
and
analyzed.
Available
multivariable
RRs
and
their
95%
CIs
will
be
included
in
the
quantitative
analysis
[12].
The
RRs
and
95%
CIs
extracted
from
the
multivariable
analysis
of
the
eligible
studies
were
pooled
for
assessing
the
predictors
of
perioperative
complications.
2.6.5.
Sensitivity
analyses
Sensitivity
analyses
were
performed
as
appropriate.
A
transformation
of
Q
test,
the
I
2
statistic
(I
2
=
100%
[Q
–
df]/Q),
was
used
to
measure
the
consistency
of
the
effect
sizes.
In
case
of
heterogeneity,
the
meta-analysis
was
performed
applying
the
random-effect
model.
An
I
2
value
of
<30%
was
defined
to
denote
low
heterogeneity,
a
value
between
30%
and
50%
was
defined
as
moderate
heteroge-
neity,
and
a
value
of
>50%
was
defined
as
high
heterogene-
ity
[13].
Egger’s
regression
model
and
funnel
plots
were
examined
to
evaluate
publication
bias.
All
tests
were
two
sided,
with
p
<
0.05
considered
as
indicative
of
statistical
significance.
Cumulative
meta-analysis
of
comparative
studies
was
conducted
using
Review
Manager
5.3
(Cochrane
Collaboration,
Oxford,
UK).
2.7.
Risk
of
bias
Two
paired
investigators
(G.E.C.
and
M.M.)
independently
weighed
the
risk
of
bias
for
all
the
studies
according
to
the
Cochrane
Handbook
for
Systematic
Reviews
of
Interven-
tions
for
including
nonrandomized
studies
[12].
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
4
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
3.
Evidence
synthesis
3.1.
Quantity
of
evidence
identified
and
characteristics
of
the
studies
included
Our
electronic
search
identified
a
total
of
3646
records
(Fig.
2).
From
these,
748
publications
were
selected
for
detailed
review.
This
yielded
176
studies
reporting
the
impact
of
PLND
and
its
extent
on
perioperative
complica-
tions
and
morbidity
in
patients
with
PCa,
which
met
the
criteria
for
inclusion
in
the
pooled
analysis:
113
(64.2%)
retrospective
studies,
54
(31.5%)
prospective
studies,
and
eight
(4.7%)
randomized
controlled
trials
were
available
for
review.
A
total
of
85
(48.2%)
studies
had
a
comparative
Fig.
2
–
PRISMA
flowchart.
LNs
=
lymph
nodes;
PLND
=
pelvic
lymph
node
dissection;
PRISMA
=
Preferred
Reporting
Items
for
Systematic
Reviews
and
Meta-analyses;
RP
=
radical
prostatectomy;
WoS
=
Web
of
Science.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
5
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
design,
of
which
eight
(4.5%)
studies
compared
RP
alone
versus
PLND
(any)
[14–21]
and
19
(10.7%)
studies
compared
RP
+
sPLND
or
lPLND
versus
RP
+
ePLND
[6,7,16,22–37];
single-
and
non–single-surgeon
series
were
reported
in
45
(25.5%)
and
64
(36.3%)
studies,
respectively.
Our
systematic
review
and
pooled
analysis
included
a
total
of
77
303
patients.
Details
of
study
characteristics
are
reported
in
Supplementary
Table
1.
The
mean
length
of
reported
follow-up
was
18. 4
mo.
The
overall
risk
of
bias
in
this
study
was
judged
to
be
moderate
to
Fig.
3
–
(A)
Global
quality
assessment
of
preoperative
complication
reporting.
(B)
Complication
comparison
of
quality
assessment
criteria
following
EAU
GL
recommendation.
The
denominator
is
the
total
number
of
publications
reporting
each
item
out
of
the
total
number
of
publications
included
in
the
present
systematic
review.
a
Item
assessed
only
for
papers
published
after
the
introduction
of
the
Clavien-Dindo
classification.
ASA
=
American
Society
of
Anesthesiologists;
CCI
=
Charlson
comorbidity
index;
EAU
GL
=
European
Association
of
Urology
guideline;
ECOG
=
Eastern
Cooperative
Oncology
Group.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
6
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
high
due
to
the
LOE
of
studies
and
heterogeneity
of
PLND
boundaries
and
outcome
reporting
(Supplementary
material).
3.2.
Quality
assessment
of
complication
grading
and
reporting
Figure
3A
depicts
the
overall
complication
assessment
after
any
PLND.
The
most
reported
item
was
the
inclusion
of
specific
procedure
complications
(84.7),
while
we
found
a
lack
of
information
regarding
the
person
who
collected
the
data
(2.8)
and
whether
she/he
was
involved
in
the
treatment
(1.7%).
When
comparing
the
assessment
of
the
quality
of
reporting
criteria
before
and
after
the
EAU
Ad
Hoc
Panel
recommendations
(Fig.
3B),
no
differences
were
found
in
terms
of
identification
of
the
person
who
collected
the
data
(2%
vs
3.8%;
p
=
0.46);
outpatient
information
(33.3%
vs
44.1%;
p
=
0.16);
readmissions
and
causes
(10.1%
vs
16. 8%;
p
=
0.25);
reoperations,
types,
and
causes
(26.2%
vs
25.9%;
p
=
1);
and
percentage
of
patients
lost
to
follow-up
(10.1%
vs
11.7 % ;
p
=
0.8).
The
percentages
of
outcome
reporting
are
as
follows:
mortality
rate
and
causes
of
death
(34.3%
vs
22%;
p
=
0.1),
definitions
of
complications
(63.6%
vs
62.3%;
p
=
0.87),
postoperative
complications
presented
in
a
table
either
by
grade
or
by
complication
type
(58.5%
vs
70.1%;
p
=
0.2),
morbidity
rate
and
total
complication
indicated
(78.7%
vs
77.9%;
p
=
1),
length
of
stay
data
(52.5%
vs
41.5;
p
=
0.17),
and
how
data
were
accrued
(chart,
review
of
face
to
face
interview;
29.2%
vs
22.0%;
p
=
0.30).
Ninety-nine
studies
were
published
before
2012
and
77
after
2012.
An
improvement
in
reporting
was
seen
in
the
following
outcomes:
defining
methods
of
accruing
data
(66.6%
vs
89.6%;
p
<
0.001),
inclusion
of
duration
of
follow-
up
(52.5%
vs
74%;
p
=
0.005),
separate
reporting
of
intra-
and
postoperative
complications
(43.4%
vs
29.3%;
p
=
0.08),
procedure-specific
complications
(80.8%
vs
92.2%;
p
=
0.04),
severity
grade
(25.2%
vs
67.5%;
p
<
0.001),
and
risk
factors
included
in
analysis
(12.1%
vs
35.0%;
p
=
0.002).
3.3.
Discrete
categorization
for
intraoperative
complications
Literature
screening
identified
84
(47.7%)
studies
that
described
intraoperative
complications
as
an
outcome
of
interest,
combining
data
on
28
428
patients.
Study
details
are
shown
in
Supplementary
Table
2.
Overall,19
(22.6%)
and
65
(77.4%)
studies
reported
zero
and
one
or
more
intraoperative
complications,
respectively.
Single-
versus
multiple-surgeon
series
(1.6%
vs
1.7%)
showed
no
differ-
ences
in
terms
of
intraoperative
complication
reporting.
Overall,
534
(1.8%)
patients
reported
at
least
one
intraop-
erative
complication
with
a
reported
range
between
0%
and
25%.
Rectal
injury
was
reported
as
the
most
common
complication
(38.2%).
Intraoperative
complications
strongly
related
to
PLND
(overall
11.6%)
were
obturator
nerve
injury
(6.54%)
and
internal
(2.0%)
and
external
(1%)
iliac
vessel
injuries.
Intraoperative
complications
likely
related
to
PLND
(overall
29.4%)
were
ureteral
injury
(12.4%)
and
bleeding
(17%).
Intraoperative
complications
unlikely
related
to
PLND
represented
58.8%.
Granular
details
of
each
intraop-
erative
complication
pattern
are
described
in
Figure
4A.
A
complete
list
of
intraoperative
complications
reported
is
available
in
the
Supplementary
material.
3.4.
Discrete
categorization
for
postoperative
complications
Literature
screening
led
to
151
(85.7%)
studies
that
described
postoperative
complications
as
an
outcome
of
interest,
combining
data
on
73
629
patients
(Supplementa-
ry
Table
2).
Fourteen
(9.2%)
and
137
(90.7%)
studies
reported
no
and
one
or
more
postoperative
complications,
respectively.
Overall,
10
401
(14.1%)
patients
reported
at
least
one
postoperative
complication.
The
total
number
of
postoper-
ative
complications
reported
was
10
853.
Study
details
are
shown
in
Supplementary
Tables
1
and
2.
A
total
of
133
(75.6%)
studies
reporting
data
on
69
963
patients
reported
8427
postoperative
complications
divided
by
discrete
categorization,
as
reported
in
Table
1.
Of
note,
our
pooled
analysis
highlighted
that
the
lymphatic
system
morbidities
were
reported
as
the
most
common
postoperative
compli-
cation
(n
=
2936,
34.8%).
The
pooled
analysis
showed
that
the
most
reported
postoperative
complications
strongly
related
to
PLND
were
lymphoceles
(2660;
90.6%),
of
which
1037
(49.1%)
were
symptomatic
and
75
(2.7%)
were
reported
to
be
infected
at
the
time
of
diagnoses.
A
total
of
883
(33.1%)
lymphoceles
were
drained
surgically
or
percutaneously,
and
five
(0.2%)
recurred
during
the
follow-up.
Other
postoperative
com-
plications
strongly
related
to
PLND
were
131
(4.5%)
lymphedemas
(not
specified),
125
(4.3%)
acute
and
16
(0.5%)
chronic
cases
of
lymphorrhea,
and
two
(0.1%)
cases
of
lymphatic
fistula.
The
most
reported
postoperative
com-
plications
likely
related
to
PLND
(pooled
count
1067;
12.6%)
were
major
thromboembolic
events
(TEEs)
including
259
(21.8%)
cases
of
deep
vein
thrombosis
and
181
(17%)
of
pulmonary
embolism,
217
(20.3%)
pelvic
hematomas
with
or
without
infection,
127
(11.9%)
edema
or
swelling
at
lower
extremities,
65
(6.1%)
edema/swelling/hematoma
around
penis,
54
(5.1%)
edema
or
swelling
of
the
groin
and
scrotal
region,
and
49
(4.6%)
obturator
nerve
palsy
due
to
damage.
Of
note,
one
study
reported
unilateral/bilateral
deep
vein
and
muscle
thrombosis
separately
[38].
Postoperative
complications
unlikely
related
to
PLND
represented
52.5%.
Granular
details
of
each
postoperative
complication
patterns
are
described
in
Figure
4B.
A
complete
list
of
the
reported
postoperative
complications
is
available
in
the
Supplementary
material.
3.5.
Limited/standard
PLND
versus
ePLND/sePLND
postoperative
complications
Nineteen
articles
compared
lPLND/sPLND
versus
ePLND/
sePLND
in
terms
of
postoperative
complications
[6,7,16,22–
37].
Our
intervention
meta-analysis
included
a
total
of
16
821
patients
of
whom
8290
(49.2%)
underwent
RP
+
lPLND/
sPLND
and
8531
(50.8%)
underwent
RP
+
ePLND/sePLND.
A
total
of
2037
(12.1%)
patients
reported
at
least
one
postoperative
complication.
The
pooled
meta-analysis
(Fig.
5A)
revealed
that
RP
+
lPLND/sPLND
has
a
statistically
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
7
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
Fig.
4
–
Assessment
of
discrete
categorization
of
perioperative
complications
of
patients
undergoing
RP
and
PLND
for
prostate
cancer:
(A)
intraoperative
complications
and
(B)
postoperative
complications.
PLND
=
pelvic
lymph
node
dissection;
RP
=
radical
prostatectomy.
Table
1
–
Discrete
categorization
of
postoperative
complications.
Type
of
postoperative
complication
No.
of
event
a
Events
(%)
a
Patients
reporting
the
complication
(%)
a
Range
of
patients
reporting
the
complication(%)
b
Any
lymphatic
complication
2936
34.8
4.2
1–63
Any
RP-related
complication
1381
16.4
2.0
1–69
Any
intra-abdominal/pelvic
bleeding
881
10.5
1.3
1–20
Any
vascular
complication
692
8.2
1.0
1–24
Any
gastrointestinal
complication
521
6.2
0.7
1–12
Any
nervous
complication
447
5.3
0.6
1–35
Any
infective
complication
329
3.9
0.5
1–28
Any
genitourinary
complication
258
3.1
0.4
1–19
c
Any
wound
complication
222
2.6
0.3
1–16
Any
cardiopulmonary
complication
137
1.6
0.2
1–6
Any
others
623
7.4
0.9
1–28
RP
=
radical
prostatectomy.
a
Considering
only
the
studies
that
specified
the
discrete
categorization
of
postoperative
events.
b
Considering
only
the
studies
that
reported
at
least
one
event
specifically
for
each
category.
c
Excluding
the
infections
that
are
reported
in
the
specific
category.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
8
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
significantly
decreased
risk
of
any
intraoperative
complica-
tions
(RR:
0.55;
95%
CI:0.35,
0.87;
p
=
0.01).
The
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
a
nonstatistically
significant
trend
in
favor
of
RP
+
lPLND/sPLND
over
ePLND/sePLND
when
performed
laparoscopically
(RR:
0.62;
95%
CI:
0.24,
1.59;
p
=
0.32)
and
robotically
(RR:
0.49;
95%
CI:
0.22,
1.10;
p
=
0.09).
There
was
no
statistical
difference
in
overall
postoperative
complications
according
to
the
extent
of
PLND
(RR:
0.53;
95%
CI:
0.08,
3.70;
p
=
0.52;
Fig.
5B).
The
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
a
statistically
significantly
deceased
risk
of
any
postoperative
complications
in
favor
of
RP
+
lPLND/sPLND
over
ePLND/sePLND
when
performed
in
open
surgery
(RR:
0.50;
95%
CI:
0.28,
0.88;
p
=
0.02),
and
no
statistically
significant
differences
for
studies
that
reported
only
laparoscopic
(RR:
1.16;
95%
CI:
0.78,
1.7 3 ;
p
=
0.46)
and
robotic
(RR:
0.64;
95%
CI:
0.12,
3.59;
p
=
0.62)
approaches.
Sensitivity
analyses
according
to
the
definitions
of
PLND-
related
postoperative
complications
were
undertaken.
A
subanalysis
revealed
that
RP
+
lPLND/sPLND
had
a
statisti-
cally
significantly
decreased
risk
of
experiencing
postoper-
ative
complications
strongly
related
to
PLND
(RR:
0.46;
95%
CI:
0.34,
0.61;
p
=
0.01;
Fig.
6A).
The
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
a
statistically
significantly
reduced
risk
of
postoperative
complications
strongly
related
to
PLND
in
favor
of
RP
+
lPLND/sPLND
over
ePLND/sePLND
when
performed
in
open
fashion
(RR:
0.42;
95%
CI:
0.31,
0.57;
p
<
0.0001)
and
robotically
(RR:
0.43;
95%
CI:
0.24,
0.77;
p
=
0.005).
Specifically,
in
terms
of
lymphocele
formation,
we
recorded
a
statistically
significant
advantage
for
RP
+
lPLND/
sPLND
over
RP
+
ePLND/sePLND
(RR:
0.52;
95%
CI:
0.37,
0.74;
p
=
0.0003;
Fig.
7A).
The
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
a
statistically
significantly
reduced
risk
of
lymphocele
forma-
tion
in
favor
of
RP
+
lPLND/sPLND
over
ePLND/sePLND
when
performed
in
open
fashion
(RR:
0.55;
95%
CI:
0.35,
0.87;
p
=
0.01)
and
robotically
(RR:
0.41;
95%
CI:
0.27,
0.63;
p
<
0.0001).
A
nonstatistically
significant
trend
in
favor
of
RP
+
lPLND/sPLND
was
found
in
terms
of
postoperative
compli-
cations
likely
(RR:
0.65;
95%
CI:
0.41,
1.05;
p
=
0.08)
and
unlikely
(RR:
0.81;
95%
CI:
0.64,
1.02;
p
=
0.08)
related
to
PLND
(Fig.
6B
and
6C).
In
this
regard,
the
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
comparable
non-statistically
signifi-
Fig.
5
–
Intervention
meta-analysis
of
studies
comparing
limited/standard
PLND
versus
extended/superextended
PLND:
(A)
intraoperative
complications
(cumulative)
and
(B)
postoperative
complications
(cumulative).
CI
=
confidence
interval;
df
=
degree
of
freedom;
M-H
=
Mantel-Haenszel;
PLND
=
pelvic
lymph
node
dissection;
RR
=
risk
ratio.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
9
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
Fig.
6
–
Intervention
meta-analysis
of
studies
comparing
limited/standard
PLND
versus
extended/superextended
PLND:
(A)
postoperative
complications
strongly
related
to
PLND,
(B)
postoperative
complications
likely
related
to
PLND,
and
(C)
postoperative
complications
unlikely
related
to
PLND.
CI
=
confidence
interval;
df
=
degree
of
freedom;
M-H
=
Mantel-Haenszel;
PLND
=
pelvic
lymph
node
dissection;
RR
=
risk
ratio.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
10
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
cant
differences.
Specifically,
in
terms
of
major
postopera-
tive
TEEs,
we
recorded
a
statistically
significant
advantage
for
RP
+
lPLND/sPLND
over
RP
+
ePLND/sePLND
(RR:
0.59;
95%CI:
0.40,
0.87;
p
=
0.008;
Fig.
7B).
The
subgroup
analysis
(Supplementary
material)
considering
the
surgical
approaches
showed
a
statistically
significantly
reduced
risk
of
postoperative
TEEs
in
favor
of
RP
+
lPLND/sPLND
over
ePLND/sePLND
when
performed
in
open
fashion
(RR:
0.56;
95%
CI:
0.35,
0.92;
p
=
0.02),
but
no
statistically
significant
differences
when
carried
out
laparoscopically
(RR:
0.56;
95%
CI:
0.35,
0.92;
p
=
0.02)
or
without
using
laparoscopy
(RR:
1.36;
95%
CI:
0.34,
5.50;
p
=
0.66).
3.6.
Predictors
for
postoperative
complications
strongly
related
to
PLND
Twelve
studies
reported
multivariable
analysis
of
predictors
of
symptomatic
lymphocele
development
[7,15,28,39–
47].
Data
from
12
932
patients
have
been
included,
and
106 5
(8.2%)
lymphocele
formations
were
reported
during
Fig.
7
–
Intervention
meta-analysis
of
studies
comparing
limited/standard
PLND
versus
extended/superextended
PLND
in
terms
of
(A)
lymphocele
formation
and
(B)
major
thromboembolic
events.
CI
=
confidence
interval;
df
=
degree
of
freedom;
M-H
=
Mantel-Haenszel;
PLND
=
pelvic
lymph
node
dissection;
RR
=
risk
ratio;
TEE
=
thromboembolic
events.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
11
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
follow-up.
Ten
studies
investigated
the
association
of
the
extent
of
PLND
and
lymphocele
formation
[7,15,28,39,40–
47].
The
pooled
meta-analysis
(Fig.
8)
revealed
that
patients
with
a
higher
number
of
lymph
nodes
retrieved
had
an
increased
risk
of
lymphocele
formation
compared
with
patients
with
a
lower
number
of
lymph
nodes
retrieved
(RR:
1.7 7 ;
95%
CI:
1.45,
2.16;
p
<
0.00001).
Sensitivity
analyses,
according
to
the
extent
of
PLND,
were
undertaken
and
displayed
separately.
The
pooled
analysis
confirmed
a
higher
positive
lymph
node
count
(RR:
2.4;
95%
CI:
1.34,
4.46;
p
=
0.004),
extracapsular
extension
(RR:
4.81;
95%
CI:
1.80,
12.89;
p
=
0.002),
and
use
of
prophylactic
low-
molecular-weight
heparin
(RR:
6.7;
95%
CI:
1.19,
37.73;
p
=
0.03)
as
predictors
for
symptomatic
lymphocele
formation.
Although
other
predictors
have
been
reported
(ie,
surgical
approach,
seminal
vesical
invasion,
prostate
volume,
and
number
of
drains),
insufficient
data
were
available
to
analyze
these
in
a
pooled
fashion
(Supplemen-
tary
material).
3.7.
Salvage
PLND
perioperative
complications
A
total
of
six
studies
reported
perioperative
complications
in
patients
undergoing
salPLND
as
an
outcome
of
interest.
Study
details
are
shown
in
Supplementary
Table
2.
Literature
screening
identified
four
and
six
studies
describing,
respec-
tively,
intra-
and
postoperative
complications
as
an
outcome
of
interest,
combining
data
on
175
patients.
Overall,
five
(4.4%)
and
42
(33.3%)
patients
reported
intra-
and
postoper-
ative
complications,
respectively.
Among
the
postoperative
complications,
those
“strongly
related
to
PLND”
(28.8%)
and
TEEs
(28.8%)
are
most
reported.
Fig.
8
–
Effect
of
PLND
extent
on
lymphocele
formation.
Pooled
(red
diamond)
and
sensitivity
(black
diamonds)
analyses,
according
to
PLND
extent
definition,
were
performed.
CI
=
confidence
interval;
df
=
degree
of
freedom;
ePLND
=
extended
PLND;
IV
=
inverse
variance;
LC
=
lymphocele;
LNs
=
lymph
nodes;
ORP
=
open
radical
prostatectomy;
PLND
=
pelvic
lymph
node
dissection;
RR
=
risk
ratio;
SE
=
standard
error.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
12
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
3.8.
Discussion
Our
systematic
review
and
meta-analysis
confirm
that
the
extent
of
PLND
impacts
perioperative
complications
in
patients
undergoing
RP
and
PLND
for
PCa,
with
ePLND
and
sePLND
being
associated
with
higher
intra-
and
postopera-
tive
complication
rates
when
than
lPLND/sPLND.
The
choice
of
the
correct
outcome
reporting
tool
is
of
paramount
importance
and
failing
to
select
the
right
one
could
lead
to
reporting
of
misleading
data
[48,49].
Globally,
the
quality
of
complication
reporting
is
not
adequate.
Several
studies
did
not
report
the
postoperative
complica-
tions
correctly
[9,50,51],
and
only
half
of
the
studies
considered
intraoperative
complications
as
an
outcome
of
interest.
The
present
systematic
review
revealed
a
weakness
in
the
literature
for
reporting
and
grading
of
intraoperative
complications
during
RP
and
PLND.
Our
analysis
found
that
about
50%
of
studies
reported
intraoperative
complications
as
an
outcome
of
interest,
and
no
study
used
published
grading
tools
[52–54].
When
considering
surgical
series
that
reported
intraoperative
complications
as
an
outcome
of
interest,
we
found
that
only
1.8%
of
patients
reported
at
least
one
intraoperative
complication,
with
obturator
nerve
injury
(52.5%)
and
iliac
vessel
injuries
(22.1%)
as
the
most
commonly
reported
PLND-related
intraoperative
complica-
tions.
The
notable
low
rate
of
intraoperative
complications
reported
may
be
the
result
of
an
absence
of
consensus
for
grading
intraoperative
complications.
Similar
results
have
been
found
for
studies
reporting
other
urologic-oncologic
surgical
procedures
[55,56].
Our
data
demonstrate
that
the
EAU
recommendations
on
postoperative
complication
reporting
[9]
have
had
a
positive
impact
on
complication
reporting
for
RP
and
PLND.
Specifically,
there
has
been
improved
reporting
of
the
methods
of
accruing
data,
duration
of
follow-up,
separation
of
intra-
and
postoperative
complications,
procedure-
specific
complications,
severity
grade,
and
patient
risk
factors.
This
is
an
encouraging
step
toward
standardizing
complication
reporting;
however,
more
work
in
standardi-
zation
is
needed
to
improve
the
comparability
of
publica-
tions
further.
Our
analysis
revealed
that
14.1%
of
patients
undergoing
RP
and
PLND
experienced
at
least
one
postoperative
complication
during
follow-up.
Lymphatic
system–related
postoperative
morbidities
were
the
most
common
postop-
erative
complications
reported,
representing
about
one-
third
of
all
postoperative
complications.
Among
the
postoperative
complications
strongly
related
to
PLND,
lymphocele
formation
was
most
common
(91%).
Of
note,
few
studies
reported
on
whether
the
lymphocele
was
symptomatic
at
the
time
of
diagnosis
and
how
it
was
managed.
When
we
compared
the
RRs
of
developing
any
lymphocele
during
the
postoperative
period,
our
analysis
found
that
a
more
extended
PLND
is
significantly
associated
with
a
nearly
two-fold
increased
risk
of
lymphocele
formation
during
the
follow-up.
Importantly,
our
inverse
variance
meta-analysis
confirmed
ePLND
as
an
independent
predictor
of
lymphocele
formation.
In
this
regard,
it
might
be
helpful
to
perform
pelvic
ultrasound
at
1
and
3
mo
for
monitoring
pelvic
lymphocele
formation
and
treat
it
accordingly.
Further
investigations
are
needed
in
order
to
better
advice
on
this
topic.
Major
TEEs
included
deep
vein
thrombosis
and
possibly
resultant
pulmonary
embolism.
Our
analysis
demonstrated
that
these
events
overall
represent
41.3%
of
all
the
postoperative
complications
“likely”
related
to
PLND.
When
we
compared
the
RRs
of
developing
any
major
TEEs
during
the
postoperative
period,
our
analysis
found
that
a
more
extended
PLND
is
significantly
associated
with
a
nearly
two-
fold
increased
risk
of
TEEs
during
the
follow-up.
Several
factors
could
be
related
to
these
life-threatening
events,
including
hypercoagulability,
vascular
injury,
immobility
after
surgery,
and
venous
stasis.
Of
note,
lymphocele
formation
could
lead
to
obstructed
venous
return,
increas-
ing
the
risk
of
TEEs.
Musch
et
al
[42]
evaluated
the
perioperative
complications
associated
with
PLND
in
1380
patients
undergoing
RP.
They
found
that
lymphocele
formation
depended
on
the
extent
of
PLND
and
the
number
of
lymph
nodes
removed.
Notably,
TEEs
and
reinterventions
were
more
frequent
in
patients
with
a
lymphocele,
highlighting
the
importance
of
customized
follow-up
in
patients
depending
on
their
proclivity
toward
postoperative
complications
strongly
or
likely
related
to
PLND.
In
order
to
improve
and
standardize
the
reporting
of
perioperative
morbidity
in
the
literature,
we
propose
a
new
assessment
tool
for
both
intra-
and
postoperative
compli-
cations
(Table
2).
First,
an
intraoperative
complication
is
defined
as
any
adverse
event
occurring
from
the
time
the
patient
is
anesthetized
to
the
time
the
patient
is
awakened
from
surgery
[10].
A
postoperative
complication
is
defined
as
any
adverse
event
that
occurs
in
the
time
between
the
termination
of
anesthesia
and
the
30-
or
90-d
postoperative
visit
[9].
The
day
on
which
a
postoperative
complication
is
identified
and
the
duration
of
follow-up
as
either
30
or
90
d
should
be
specified.
Complications
related
to
RP
and
PLND
should
be
defined
as
those
strongly,
likely,
or
unlikely
related
to
PLND,
as
presented
in
Figure
4.
Each
event
should
be
assigned
a
severity
grade.
For
intraoperative
complica-
tions,
the
EAU
Ad
Hoc
Panel
guidelines
should
be
utilized,
which
include
eight
severity
grades
(0–5b),
ranging
from
no
intervention
required
(grade
0)
to
death
(5b)
[10].
Every
surgeon
should
include
this
within
the
operative
note.
Postoperative
complications
should
be
graded
according
to
the
Clavien-Dindo
classification
system,
which
includes
five
severity
grades
(I–V)
based
on
the
level
of
management
required
for
postoperative
complications,
ranging
from
conservative
management
(grade
I)
to
death
(V).
The
EAU
Ad
Hoc
Panel
guidelines
on
postoperative
complication
report-
ing
should
be
followed
[9].
Standardized
complication
grading
ensures
that
intra-
and
postoperative
complication
rates
can
be
compared
more
accurately
across
papers.
Management
of
each
complication
should
be
described
in
detail,
specifically
whether
it
required
medical
or
surgical
intervention,
and
whether
it
was
managed
intra-
or
postoperatively.
The
number
(%)
of
patients
who
have
reported
at
least
one
complication,
the
number
(%)
of
patients
who
reported
a
specific
complication,
and
the
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
13
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
number
of
complications
should
be
described
separately.
Finally,
any
postoperative
sequelae
and
subsequent
man-
agement
related
to
the
complication
after
the
initial
follow-
up
period
should
be
presented.
Given
the
high-rate
of
perioperative
complications
strongly
and
likely
related
to
PLND,
proper
patient
selection
before
the
surgery
[1,57–60]
and
a
tightened
follow-up
for
patients
according
to
PLND
extension
are
of
utmost
importance.
More
standardized
reporting
of
intra-
and
postoperative
complications
is
needed
to
better
understand
the
direct
impact
on
patients’
perioperative
outcomes.
The
new
classification
proposed
may
improve
PLND-related
outcome
reporting.
This
new
information
is
of
considerable
interest
and
practical
use,
and
has
important
implications
for
both
academic
and
clinical
practice.
Editors
and
reviewers
should
suggest
reporting
complications
as
an
outcome
of
interest.
The
choice
of
the
correct
outcome
reporting
tool
is
of
paramount
importance,
and
failing
to
choose
the
right
one
could
potentially
lead
to
reporting
data
that
are
far
from
reality.
On
the
other
side,
surgeons
should
properly
report
complications
in
order
to
follow
their
possible
impact
on
the
patient’s
postoperative
course.
To
the
best
of
our
knowledge,
the
present
study
is
the
first
to
systematically
analyze
the
impact
of
PLND
extent
on
PLND-related
perioperative
complications.
Limitations
in-
clude
a
moderate
to
high
risk
of
bias
in
most
of
the
domains.
There
is
also
significant
heterogeneity
between
studies
in
terms
of
defining
the
boundaries
of
their
PLND
template.
In
several
cases,
the
extent
of
PLND
was
not
described
in
detail,
and
for
this
reason,
it
was
not
possible
to
categorize
them.
Finally,
an
important
limitation
is
the
overall
suboptimal
LOE
of
publications
in
this
field.
To
date,
only
4%
LOE
I
exists
regarding
this
field.
Oxford
LOEs
were
II,
III,
and
IV
in
18%,
42%,
and
36%
of
publications,
respectively.
Most
studies
included
prospective
or
retrospective
comparisons
of
heterogeneous
groups.
4.
Conclusions
The
perioperative
morbidity
of
PLND
in
patients
undergoing
RP
and
PLND
for
PCa
largely
depends
on
the
extent
of
lymphadenectomy.
More
standardized
reporting
of
intra-
and
postoperative
complications
is
needed
to
better
understand
the
direct
impact
on
patients’
perioperative
outcomes.
The
new
classification
proposed
may
improve
PLND-related
outcome
reporting.
Although
the
therapeutic
role
of
PLND
during
RP
is
still
controversial,
its
extension
can
be
associated
with
complication
rates.
The
present
study's
findings
might
help
provide
pertinent
evidence
for
updating
the
current
guidelines
in
terms
of
patient
selection.
Author
contributions:
Giovanni
E.
Cacciamani
had
full
access
to
all
the
data
in
the
study
and
takes
responsibility
for
the
integrity
of
the
data
and
the
accuracy
of
the
data
analysis.
Study
concept
and
design:
Cacciamani,
I.
Gill,
Briganti,
Montorsi.
Acquisition
of
data:
Mass,
Nassiri,
Ortega,
K.
Gill.
Analysis
and
interpretation
of
data:
Cacciamani,
I.
Gill,
Montorsi.
Drafting
of
the
manuscript:
Cacciamani,
Montorsi.
Critical
revision
of
the
manuscript
for
important
intellectual
content:
Thalmann,
Heidenreich,
Eastham,
Evans,
Karnes,
Dell’Oglio,
Abreu,
Briganti,
Artibani,
I.
Gill,
Montorsi.
Statistical
analysis:
Cacciamani.
Obtaining
funding:
None.
Administrative,
technical,
or
material
support:
None.
Supervision:
Montorsi.
Other:
None.
Financial
disclosures:
Giovanni
E.
Cacciamani
certifies
that
all
conflicts
of
interest,
including
specific
financial
interests
and
relationships
and
affiliations
relevant
to
the
subject
matter
or
materials
discussed
in
the
manuscript
(eg,
employment/affiliation,
grants
or
funding,
consultan-
cies,
honoraria,
stock
ownership
or
options,
expert
testimony,
royalties,
or
patents
filed,
received,
or
pending),
are
the
following:
None.
Funding/Support
and
role
of
the
sponsor:
None.
Appendix
A.
Supplementary
data
Supplementary
material
related
to
this
article
can
be
found,
in
the
online
version,
at
doi:https://doi.org/10.1016/j.
euo.2021.02.001.
References
[1]
Mottet
N.,
Bellmunt
J.,
Briers
E.,
et
al.
EAU
–
ESTRO
–
ESUR
–
SIOG
guidelines
on
prostate
cancer.
Presented
at
the
EAU
Annual
Con-
Table
2
–
Proposal
for
complication
reporting
guidelines.
Type
of
complication
Grading
Management
Perioperative
sequelae
Timing
Intraoperative
complications
Strongly
to
be
related
to
PLND
Grade
according
to
the
EAU
Ad
Hoc
Panel
guidelines
Report
how
an
intraoperative
complication
was
managed
during
the
operation
Describe
the
impact
of
an
intraoperative
complication
and
subsequent
management
on
the
postoperative
course
Include
any
intraoperative
complication
that
occurred
between
anesthesia
initiation
and
termination
Likely
to
be
related
to
PLND
Unlikely
to
be
related
to
PLND
Postoperative
complications
Strongly
to
be
related
to
PLND
Grade
according
to
the
Clavien-Dindo
classification
and
according
the
EAU
Ad
Hoc
Panel
guidelines
Report
postoperative
complication
management
during
the
postoperative
course
Describe
the
impact
of
a
postoperative
complication
and
subsequent
management
on
the
postoperative
course
Include
any
postoperative
complications
that
occurred
between
anesthesia
termination
and
either
the
30-
or
90-d
follow-up
appointment
Likely
to
be
related
to
PLND
Unlikely
to
be
related
to
PLND
EAU
=
European
Association
of
Urology;
PLND
=
pelvic
lymph
node
dissection.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
14
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
gress
Amsterdam
2020.
978-94-92671-07-3.
Arnhem,
The
Netherlands:
EAU
Guidelines
Office;
2020.
[2]
Fujimoto
N,
Shiota
M,
Tomisaki
I,
Minato
A,
Yahara
K.
Reconsidera-
tion
on
clinical
benefit
of
pelvic
lymph
node
dissection
during
radical
prostatectomy
for
clinically
localized
prostate
cancer.
Urol
Int
2019;103:125–36.
[3]
Fossati
N,
et
al.
The
benefits
and
harms
of
different
extents
of
lymph
node
dissection
during
radical
prostatectomy
for
prostate
cancer:
a
systematic
review.
Eur
Urol
2017;72:84–109.
[4]
Sarkar
RR,
et
al.
Association
between
radical
prostatectomy
and
survival
in
men
with
clinically
node-positive
prostate
cancer.
Eur
Urol
Oncol
2019;2:584–8.
[5]
Petersen
LJ,
Zacho
HD.
PSMA
PET
for
primary
lymph
node
staging
of
intermediate
and
high-risk
prostate
cancer:
an
expedited
system-
atic
review.
Cancer
Imaging
2020;20:10.
[6]
Clark
T,
et
al.
Randomized
prospective
evaluation
of
extended
versus
limited
lymph
node
dissection
in
patients
with
clinically
localized
prostate
cancer.
J
Urol
2003;169:145–7.
[7]
Briganti
A,
et
al.
Complications
and
other
surgical
outcomes
asso-
ciated
with
extended
pelvic
lymphadenectomy
in
men
with
local-
ized
prostate
cancer.
Eur
Urol
2006;50:1006–13.
[8]
Tsaur
I,
Thomas
C.
Risk
factors,
complications
and
management
of
lymphocele
formation
after
radical
prostatectomy:
a
mini-review.
Int
J
Urol
2019;26:711–6.
[9]
Mitropoulos
D,
et
al.
Reporting
and
grading
of
complications
after
urologic
surgical
procedures:
an
ad
hoc
EAU
guidelines
panel
assessment
and
recommendations.
Eur
Urol
2012;61:341–9.
[10]
Biyani
CS,
Pecanka
J,
Rouprêt
M,
Jensen
JB,
Mitropoulos
D.
Intra-
operative
Adverse
Incident
Classification
(EAUiaiC)
by
the
European
Association
of
Urology
ad
hoc
Complications
Guidelines
Panel.
Eur
Urol
2020;77:601–10.
[11]
Moher
D,
Liberati
A,
Tetzlaff
J,
Altman
DG,
PRISMA
Group.
Preferred
reporting
items
for
systematic
reviews
and
meta-analyses:
the
PRISMA
Statement.
PLoS
Med
2009;3:e1000097.
[12]
Higgins
J.
G.
S.
Cochrane
handbook
for
systematic
reviews
of
inter-
ventions,
version
6.0.
London:
The
Cochrane
Collaboration;
2019.
[13]
Higgins
JPT,
Thomas
J,
Chandler
J,
et
al.
Cochrane
handbook
for
systematic
reviews
of
interventions,
version
5.1.0
(updated
March
2011).
London:
The
Cochrane
Collaboration;
2011.
[14]
Eifler
JB,
Levinson
AW,
Hyndman
ME,
Trock
BJ,
Pavlovich
CP.
Pelvic
lymph
node
dissection
is
associated
with
symptomatic
venous
thromboembolism
risk
during
laparoscopic
radical
prostatectomy.
J
Urol
2011;185:1661–5.
[15]
Khoder
WY,
et
al.
Risk
factors
for
pelvic
lymphoceles
post-radical
prostatectomy.
Int
J
Urol
2011;18:638–43.
[16]
Liss
MA,
et
al.
Outcomes
and
complications
of
pelvic
lymph
node
dissection
during
robotic-assisted
radical
prostatectomy.
World
J
Urol
2013;31:481–8.
[17]
Touijer
K,
et
al.
Extending
the
indications
and
anatomical
limits
of
pelvic
lymph
node
dissection
for
prostate
cancer:
improved
staging
or
increased
morbidity?
BJU
Int
2011;108:372–7.
[18]
Tyritzis
SI,
et
al.
Thromboembolic
complications
in
3,544
patients
undergoing
radical
prostatectomy
with
or
without
lymph
node
dissection.
J
Urol
2015;193:117–25.
[19]
Van
Der
Poel
HG,
De
Blok
W,
Tillier
C,
Van
Muilekom
E.
Robot-
assisted
laparoscopic
prostatectomy:
nodal
dissection
results
dur-
ing
the
first
440
cases
by
two
surgeons.
J
Endourol
2012;26:1618–
24.
[20]
Zorn
KC,
et
al.
Pelvic
lymphadenectomy
during
robot-assisted
radical
prostatectomy:
assessing
nodal
yield,
perioperative
out-
comes,
and
complications.
Urology
2009;74:296–302.
[21]
Lin
BM,
et
al.
Incidence
and
risk
factors
for
inguinal
and
incisional
hernia
after
laparoscopic
radical
prostatectomy.
Urology
2011;77:957–62.
[22]
Heidenreich
A,
Varga
Z,
Von
Knobloch
R.
Extended
pelvic
lymphadenectomy
in
patients
undergoing
radical
prostatectomy:
high
incidence
of
lymph
node
metastasis.
J
Urol
2002;167:1681–6.
[23]
Klevecka
V,
Burmester
L,
Musch
M,
Roggenbuck
U,
Kroepfl
D.
Intraoperative
and
early
postoperative
complications
of
radical
retropubic
prostatectomy.
Urol
Int
2007;79:217–25.
[24]
Lindberg
C,
et
al.
Extended
pelvic
lymphadenectomy
for
prostate
cancer:
Will
the
previously
reported
benefits
be
reproduced
in
hospitals
with
lower
surgical
volumes?
Scand
J
Urol
Nephrol
2009;43:437–41.
[25]
Polcari
AJ,
et
al.
Comparison
of
open
and
robot-assisted
pelvic
lymphadenectomy
for
prostate
cancer.
J
Endourol
2009;23:1313–7.
[26]
Eden
CG,
Arora
A,
Rouse
P.
Extended
vs
standard
pelvic
lymphadenectomy
during
laparoscopic
radical
prostatectomy
for
intermediate-
and
high-risk
prostate
cancer.
BJU
Int
2010;106:537–
42.
[27]
Katz
DJ,
et
al.
Lymph
node
dissection
during
robotic-assisted
lapa-
roscopic
prostatectomy:
comparison
of
lymph
node
yield
and
clinical
outcomes
when
including
common
iliac
nodes
with
stan-
dard
template
dissection.
BJU
Int
2010;106:391–6.
[28]
Naselli
A,
Andreatta
R,
Introini
C,
Fontana
V,
Puppo
P.
Predictors
of
symptomatic
lymphocele
after
lymph
node
excision
and
radical
prostatectomy.
Urology
2010;75:630–5.
[29]
Davis
Jw,
Shah
Jb,
Achim
M.
Robot-assisted
extended
pelvic
lymph
node
dissection
(PLND)
at
the
time
of
radical
prostatectomy
(RP):
a
video-based
illustration
of
technique,
results,
and
unmet
patient
selection
needs.
BJU
Int
2011;108:993–8.
[30]
Jung
JH,
et
al.
Extended
pelvic
lymph
node
dissection
including
internal
iliac
packet
should
be
performed
during
robot-assisted
laparoscopic
radical
prostatectomy
for
high-risk
prostate
cancer.
J
Laparoendosc
Adv
Surg
Tech
A
2012;22:785–90.
[31]
Kim
KH,
et
al.
Extended
vs
standard
lymph
node
dissection
in
robot-
assisted
radical
prostatectomy
for
intermediate-
or
high-risk
pros-
tate
cancer:
a
propensity-score-matching
analysis.
BJU
Int
2013;112:216–23.
[32]
Yuh
BE,
Ruel
NH,
Mejia
R,
Novara
G,
Wilson
TG.
Standardized
comparison
of
robot-assisted
limited
and
extended
pelvic
lymphadenectomy
for
prostate
cancer.
BJU
Int
2013;112:81–8.
[33]
Hoshi
S,
et
al.
Comparison
of
semi-extended
and
standard
lymph
node
dissection
in
radical
prostatectomy:
a
single-institute
experi-
ence.
Mol
Clin
Oncol
2015;3:1085–7.
[34]
Eden
CG,
Soares
R,
Bott
SRJ,
Hindley
RG,
McGregor
RG.
Lymph
node
parameters
and
complications
following
laparoscopic
extended
pelvic
lymphadenectomy
for
prostate
cancer
in
1000
consecutive
patients.
J
Clin
Urol
2016;9:313–20.
[35]
Mistretta
FA,
et
al.
Extended
versus
standard
pelvic
lymphadenec-
tomy
during
robot-assisted
radical
prostatectomy:
the
role
of
ex-
tended
template
as
an
independent
predictor
of
lymph
node
invasion
with
comparable
morbidity
burden.
Minerva
Urol
Nefrol
2017;69:475–85.
[36]
Altok
M,
et
al.
Surgeon-led
prostate
cancer
lymph
node
staging:
pathological
outcomes
stratified
by
robot-assisted
dissection
tem-
plates
and
patient
selection.
BJU
Int
2018;122:66–75.
[37]
Morizane
S,
et
al.
Comparison
of
the
diagnostic
efficacy
and
peri-
operative
outcomes
of
limited
versus
extended
pelvic
lymphadenectomy
during
robot-assisted
radical
prostatectomy:
a
multi-institutional
retrospective
study
in
Japan.
Int
J
Clin
Oncol
2018;23:568–75.
[38]
Breyer
BN,
Greene
KL,
Dall’Era
MA,
Davies
BJ,
Kane
CJ.
Pelvic
lymphadenectomy
in
prostate
cancer.
Prostate
Cancer
Prostatic
Dis
2008;11:320–4.
[39]
Gotto
GT,
et
al.
Predictors
of
symptomatic
lymphocele
after
radical
prostatectomy
and
bilateral
pelvic
lymph
node
dissection.
Int
J
Urol
2011;18:291–6.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
15
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
[40]
Horovitz
D,
Lu
X,
Feng
C,
Messing
EM,
Joseph
JV.
Rate
of
symptom-
atic
lymphocele
formation
after
extraperitoneal
vs
transperitoneal
robot-assisted
radical
prostatectomy
and
bilateral
pelvic
lymphadenectomy.
J
Endourol
2017;31:1037–43.
[41]
Lee
JY,
et
al.
Lymphocele
after
extraperitoneal
robot-assisted
radical
prostatectomy:
a
propensity
score-matching
study.
Int
J
Urol
2013;20:1169–76.
[42]
Musch
M,
Klevecka
V,
Roggenbuck
U,
Kroepfl
D.
Complications
of
pelvic
lymphadenectomy
in
1,380
patients
undergoing
radical
ret-
ropubic
prostatectomy
between
1993
and
2006.
J
Urol
2008;179:923–9.
[43]
Orvieto
MA,
et
al.
Incidence
of
lymphoceles
after
robot-assisted
pelvic
lymph
node
dissection.
BJU
Int
2011;108:1185–9.
[44]
Schmitges
J,
et
al.
Influence
of
low-molecular-weight
heparin
dos-
age
on
red
blood
cell
transfusion,
lymphocele
rate
and
drainage
duration
after
open
radical
prostatectomy.
Eur
J
Surg
Oncol
2012;38:1082–8.
[45]
Thomas
C,
et
al.
Incidence,
risk
factors
and
management
of
symp-
tomatic
lymphoceles
after
radical
retropubic
prostatectomy.
Urol
Pract
2017;4:493–8.
[46]
Thomas
C,
et
al.
Development
of
symptomatic
lymphoceles
after
radical
prostatectomy
and
pelvic
lymph
node
dissection
is
inde-
pendent
of
surgical
approach:
a
single-center
analysis.
Int
Urol
Nephrol
2019;51:633–40.
[47]
Van
Praet
C,
et
al.
Contemporary
minimally-invasive
extended
pelvic
lymph
node
dissection
for
prostate
cancer
before
curative
radiotherapy:
prospective
standardized
analysis
of
complications.
Int
J
Urol
2014;21:1138–43.
[48]
Artibani
W.
What
you
measure
depends
on
the
tool
you
use:
a
short
step
from
incorrect
measurements
to
fake
data.
Eur
Urol
2018;74:8–9.
[49]
Gandaglia
G,
et
al.
The
impact
of
implementation
of
the
European
Association
of
Urology
Guidelines
Panel
recommendations
on
reporting
and
grading
complications
on
perioperative
outcomes
after
robot-assisted
radical
prostatectomy.
Eur
Urol
2018;74:4–7.
[50]
Martin
2nd
RC,
Brennan
MF,
Jaques
DP.
Quality
of
complication
reporting
in
the
surgical
literature.
Ann
Surg
2002;235:803–13.
[51]
Dindo
D,
Demartines
N,
Clavien
PA.
Classification
of
surgical
com-
plications:
a
new
proposal
with
evaluation
in
a
cohort
of
6336
patients
and
results
of
a
survey.
Ann
Surg
2004;240:205–13.
[52]
Rosenthal
R,
Hoffmann
H,
Clavien
P-A,
Bucher
HC,
Dell-Kuster
S.
Definition
and
classification
of
intraoperative
complications
(CLAS-
SIC):
Delphi
study
and
pilot
evaluation.
World
J
Surg
2015;39:1663–
71.
[53]
Kaafarani
HM,
et
al.
Derivation
and
validation
of
a
novel
severity
classification
for
intraoperative
adverse
events.
J
Am
Coll
Surg
2014;218:1120–8.
[54]
Kazaryan
AM,
Røsok
BI,
Edwin
B.
Morbidity
assessment
in
surgery:
refinement
proposal
based
on
a
concept
of
perioperative
adverse
events.
ISRN
Surg
2013;2013:625093.
[55]
Cacciamani
GE,
et
al.
Impact
of
implementation
of
standardized
criteria
in
the
assessment
of
complication
reporting
after
robotic
partial
nephrectomy:
a
systematic
review.
Eur
Urol
Focus
2020;6:513–7.
[56]
Cacciamani
GE,
et
al.
Quality
assessment
of
intraoperative
adverse
event
reporting
during
29
227
robotic
partial
nephrectomies:
a
systematic
review
and
cumulative
analysis.
Eur
Urol
Oncol
2020;3:780–3.
[57]
Dell’Oglio
P,
et
al.
External
validation
of
the
European
association
of
urology
recommendations
for
pelvic
lymph
node
dissection
in
patients
treated
with
robot-assisted
radical
prostatectomy.
J
Endourol
2014;28:416–23.
[58]
Roach
3rd
M,
et
al.
Predicting
the
risk
of
lymph
node
involvement
using
the
pre-treatment
prostate
specific
antigen
and
Gleason
score
in
men
with
clinically
localized
prostate
cancer.
Int
J
Radiat
Oncol
Biol
Phys
1994;28:33–7.
[59]
Gandaglia
G,
et
al.
Development
and
internal
validation
of
a
novel
model
to
identify
the
candidates
for
extended
pelvic
lymph
node
dissection
in
prostate
cancer.
Eur
Urol
2017;72:632–40.
[60]
Briganti
A,
et
al.
Updated
nomogram
predicting
lymph
node
inva-
sion
in
patients
with
prostate
cancer
undergoing
extended
pelvic
lymph
node
dissection:
the
essential
importance
of
percentage
of
positive
cores.
Eur
Urol
2012;61:480–7.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
O
N
C
O
L
O
G
Y
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
16
EUO-424;
No.
of
Pages
16
Please
cite
this
article
in
press
as:
Cacciamani
GE,
et
al.
Impact
of
Pelvic
Lymph
Node
Dissection
and
Its
Extent
on
Perioperative
Morbidity
in
Patients
Undergoing
Radical
Prostatectomy
for
Prostate
Cancer:
A
Comprehensive
Systematic
Review
and
Meta-
analysis.
Eur
Urol
Oncol
(2021),
https://doi.org/10.1016/j.euo.2021.02.001
