18 96
and
are
thus
eligible
for
bladder-preserving
treatment
including
transurethral
resection
of
the
bladder
(TURBT)
with or without
intravesical
therapy
[2]. By
contrast, appro-
ximately
30%
of
patients
have
muscle-invasive
or
locally
advanced UCB
at diagnosis
[3],
and
radical
cystectomy
(RC)
with bilateral
lymphadenectomy with or without periopera-
tive
systemic
chemotherapy
is
the
gold
standard
treatment
for
these
patients
[4] .Despite
clear
evidence
that
tobacco
smoke
contains
over 60 carcinogens, causes at
least 18
types of cancer, and
is
the
second
leading
risk
factor
causing
death,
>
30%
of
adults
in
the Western
world
are
still
current
or
former
smokers
[5–7] .There
is
convincing evidence
that
cigarette
smoking
is
the
best-established
and most
important
risk
factor
for
the
development
of
UCB
[8,9] .The
risk
of
UCB
development
is
inversely
associated
with
age
at
first
exposure and cessation of cigarette smoking
[9]. According
to
current
smoking
patterns,
a
global
average
of
approxi-
mately
50%
of
young men
and
10%
of
young women
are
smokers
and
only
relatively
few
quit
[10]. As
these
young
smokers
reach middle
and
old
age,
the
effects
of
smoking
will
represent a
future burden
for all health
care providers
including
urologists,
as
UCB
is
generally
a
disease
of
the
elderly
[11].
UCB
has
the
highest
prevalence
among
all
urinary
tract
malignancies
because
of moderate
progression
rates
and
long-term
survival
in
many
patients
[8];
nevertheless,
UCB
screening
is
not
performed,
mainly
because
of
the
low
overall
incidence
[12].
However,
it
is
important
to
acknowledge
that UCB
is
the most expensive cancer and has
the
highest
lifetime
treatment
cost
per
patient
among
all
cancers
[13]. The necessity
for
long-termmonitoring of UCB
patients has
steadily
increased
the health economic burden
for
decades.
Together
with
long-term
disease-related
psychological
effects,
the
economic
burden
of UCB
surveil-
lance
and
treatment
underscores
the
urgent
need
for
a
better understanding of UCB risk
factors and
their
impact on
the
natural
history
of
the
disease.
It
has
been
suggested
that
smoking
not
only
promotes
carcinogenesis
but
is
also
associated with
tumor
behavior.
However, the
impact of smoking on the course of UCB disease
and outcomes
remains poorly understood and controversial.
There
is evidence
from different
smoking-related malignan-
cies
that
continuing
smoking
after
diagnosis
negatively
affects oncologic outcomes
[14] .Previous studies
investigat-
ing the effects of smoking on disease outcomes and prognosis
face importantmethodological barriers, and it is important to
realize
that
smoking
is
not
just
smoking
[15].
To
quantify
cumulative
cigarette
smoking
exposure,
the medical
con-
vention
has
favored
pack-years
(average
number
of
packs
smoked
per
day multiplied
by
smoking
duration
in
years).
This measure assumes that duration and
intensity
(packs per
day) have equivalent effects, but growing evidence
suggests
that
this
is
not
the
case.
In
addition,
long-term
smoking
cessation
decreases
the
risk
of
cardiovascular
and
lung
disease
and
the
likelihood
of
developing
various malignan-
cies
[16].
However,
whether
smoking
cessation
and
time
since
cessation beneficially
influence oncologic outcomes
in
UCB
remains
inconclusive.
Therefore,
a
better
understanding
of
smoking-related
biology
in UCB development and
the
role of smoking
in UCB
prognosis may
significantly
influence
clinical management
strategies
and
thus
health
costs.
In
this
systematic
review
we
summarize
evidence
from
the
most
recent
articles
regarding
the
effects
of
smoking
and
smoking
cessation
on
UCB development and oncologic outcomes
for patients with
NMIBC
and MIBC.
2.
Evidence
acquisition
2.1.
Search
strategy
J.J.C.
conducted
a
literature
search
in September 2014 using
the
PubMed
and
Scopus
databases.
The
following
search
was
performed:
(smok*
OR
tobacco
OR
cig*
OR
‘‘smoking
cessation’’)
AND
(cancer
OR
carcinoma
OR
neoplas*
OR
tumor)
AND
(bladder
OR
urothelial
OR
‘‘transitional
cell’’)
AND
(‘‘risk
factor’’ OR
recur* OR progression OR
survival OR
death OR mortality OR
prognos* OR
outcome).
Filters were
applied
to
capture
items
published
in
English
on
or
after
January 1, 1990.
2.2.
Study
eligibility
Our procedure
for
including studies
in this review
is outlined
in
Figure 1,
consistent with
Preferred
Reporting
Items
for
Systematic
Reviews
and Meta-analyses
[17] .M.R.
and
J.J.C.
read all
resulting abstracts and
full-text articles
in depth. All
authors agreed
that
the articles
selected
for
this
review met
the
inclusion
criteria
dictated
by
the
patient
population,
intervention/exposure,
comparison,
outcome,
and
study
design
(PICOS)
approach. A
record was
considered
relevant
to
this
review
if
it
assessed
the
following:
adult men
and
women
treated with
surgery
for
UCB;
significant
smoking
history or
smoking exposure
compared with
lesser
smoking
history
or
smoking
exposure
or
smoking
cessation;
and
diagnosis
of
UCB
and
patient
outcomes,
including
disease
recurrence or progression and cancer-specific and any-cause
mortality. We
accepted
all
study
designs
except
for
case
reports. Meeting
abstracts,
editorials,
and
commentaries on
articles were not accepted, nor were review articles or meta-
analyses.
In
an
effort
to
provide
the most
recent
data
available,
only
studies
published
in
2011
or
later
were
considered
for
associations
between
smoking
and
UCB
risk
( Fig. 1).
In
addition,
we
required
that
at
least
100
patients
were
present
in both
the
case
and
control
groups.
We
considered
all
items
published
in
1990
or
later
for
associations
between
smoking
and
outcomes
for
UCB
( Fig. 1). We
divided
studies
into
two
groups
according
to
the
intervention performed
(TURBT or RC). Cohorts
for which
both TURBT
and RC outcomes were
reported were
excluded
because
these
cohorts
were
deemed
too
heterogeneous
for
our
analysis.
We
also
required
that
the
majority
of
the
patients
had
urothelial
carcinoma
histology
and
that
there were
at
least
10
patients
in
each
smoking
status
or
exposure
group.
E U R O P E A N
U R O L O G Y
F O C U S
1
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)
1 7 – 2 7
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