21 96
3.2.
Bladder
cancer
outcomes
3.2.1.
Transurethral
resection
of
the
bladder
For
patients
treated
with
TURBT,
smoking
status
and
cumulative
lifetime
smoking
exposure
seem
to
influence
disease
prognosis
( Table 2).
The majority
of
studies
(10
of
16)
found
that
active/current
cigarette
smoking,
as well
as
high
lifetime
exposure,
significantly
increase
the
risk
of
disease
recurrence
[31–46] .There
is
only
moderate
evidence
that
smoking
increases
the
risk
of
disease
progression
in
NMIBC
(4
of
11
studies)
[33,35,37–39,41– 43,45,47,48].
In
addition,
there
is
also
no
conclusive
evidence
of
an
association
between
smoking
and
cancer-
specific
mortality
or
any-cause
mortality
in
NMIBC
[42,43,45]. The
evidence
for
these
three
endpoints, howev-
er,
is
obviously
compromised
by
a
lack
of
data
and
overall
low mortality
rates
for
patients with
NMIBC.
The
same
is
true
regarding
the
gender-specific
effect
of
smoking
on
NMIBC outcomes
[49] .The
findings are
contradictory across
studies
and
thus
no
final
conclusions
can
be
drawn.
In
addition,
findings
regarding
the
influence
of
smoking
cessation
on
outcomes
in NMIBC
are
partly
conflicting,
but
the
evidence
for
a
reduction
in
recurrence
rates
is
strongest
( Table 4 ,4 of 6 studies)
[33,34,37,40,42,43].
In addition, there
is
some
evidence
that
smoking
reduces
the
efficiency
of
intravesical
chemotherapy
and
immunotherapy
[31,35,36, 40,44,45,50]. This
finding
seems
reasonable
considering
the
immunomodulatory
effects
of
tobacco
smoke.
Although
the
current
evidence
represents
an
improve-
ment
because
of
emerging
interest
in
elucidating
the
associations between smoking and NMIBC outcomes, several
study-related
and
general
limitations
need
to
be
overcome
in
future
research.
In
general,
NMIBC
is
a
complex
and
heterogeneous disease:while some patients experience early
disease
recurrence
or
even
disease
progression,
others
remain
free
of
their
disease
for
a
long
time
if
not
forever
[8].
However,
subset
analyses
of
particular
NMIBC
risk
groups
(eg,
intermediate
vs
high
risk,
low-grade
vs
high-
grade
tumors)
are
currently
lacking. Moreover,
the
impact
of
smoking
according
to
different
treatment
modalities
(eg,
white
light
vs
photodynamic
diagnosis
for
TURBT
guidance,
repeat
TURBT)
remains
unexamined
to
the
best
of
our
knowledge.
For
risk
stratification
and
patient
counseling,
two
established models
are
frequently
used,
the
risk
tables
of
the
European
Organization
for
Research
and
Treatment
of
Cancer
and
Club
Urologico
Espanol
de
Tratamiento
Onco-
logico
(Spanish
Urological
Oncology
Group)
[2].
Recently
published
studies have challenged
the accuracy and clinical
utility
of
these models
because
of
insufficient
discrimina-
tion
[51].
In
fact, both models adjust
for
several established
risk
factors,
but
do
not
adjust
for
the
impact
of
the
best-
established
individually modifiable
risk
factor, which may
improve
outcome
predictions.
Finally, UCB carcinogenesis
is a complex process affected
by
several
inherent
genetic
and
biologic
factors,
as
well
as
geographic,
environmental,
occupational,
and
social
behavioral
elements
[52].
The majority
of
current
studies
only
controlled
for
smoking
as
a
sole
risk
factor,
and
studies
adjusting
for
combinations
of
risk
factors
are
warranted.
3.2.2.
Radical
cystectomy
There
is
some
evidence
that
smoking
impacts
disease
prognosis
in UCB patients treatedwith RC
( Table 3 ), although
this
effect was
less
apparent
compared
to
patients
treated
with TURBT. Overall, two of eight studies found that cigarette
smokingwas an independent predictor of disease recurrence,
cancer-specific mortality, or overall
survival
[53–60] .Again,
current
smoking
status
and
escalating
lifetime
smoking
exposure were
inversely
associated with
outcomes
in
these
studies.
The
highest
level
of
evidence
is
obtained
from
prospec-
tive, randomized controlled studies, but
the results reported
here
are
from
retrospective
studies with
all
the
inherent
limitations
that may
limit
the
evidence
base. Of
particular
importance
for research on smoking
is
the
fact
that smoking
status
and
exposure
are
mostly
self-reported
and
are
therefore
subject
to
recall
bias.
Validated
questionnaires
to assess smoking
in patients with cancer at different points
during
the
disease
course
are
still
being
developed
[61].
In
addition,
if
current
smokers
report
themselves
as
former
smokers,
associations
between
smoking
and
outcomes
would be biased
toward
the null, especially
if
such patients
could
not
successfully
quit
smoking
following
diagnosis.
Biochemical verification of smoking status may be a goal
for
future
investigations.
The
influence of
smoking cessation on outcomes
for UCB
patients after RC remains undetermined
( Table 4). We
found
only
one
study
addressing
this
association,
and
it
showed
that quitting smoking reduced
the risk of disease recurrence,
cancer-specificmortality, andany-causemortality
[58] .Since
there
is some evidence
that smoking
influences
the course of
UCB,
urologists
should
not
only
counsel
patients
regarding
the
detrimental
effects
of
smoking
but
also
assist
in
their
smoking
cessation
attempts
[62,63].
The
association
be-
tween smoking and UCB
is not as well known as
that
for
lung
cancer
[64]. For many patients, cancer diagnosis represents a
teachable moment
to motivate
them
to
successfully
quit
smoking.
UCB
patients
are
often
willing
to
quit
smoking
with
the
help
of
their
physicians
[65] .Appropriate
patient
education
and
brief
physician
meetings
may
increase
compliance
to ultimately cease smoking,
improve outcomes,
and
enhance
quality
of
life,
as
current
smokers
report
increased
fear
of
disease
recurrence
and
psychological
distress
compared
to
nonsmokers
[66] .However,
too
few
patients
are
currently
offered
any
intervention
to
aid
in
cessation by
their urologists
[64,67].
We
also
found
contradictory
evidence
regarding
a
gender-specific effect of
smoking
in
these patients.
Interest-
ingly,
previous
studies
reported
gender-specific
differences
in MIBC outcomes: women presented with more aggressive
tumor biology and unfavorable sequelae
[68]. Thus, this
issue
should
be
the
subject
of
future
investigations
to
clarify
the
effect
of
smoking
on
these
variations.
As
with
NMIBC,
research
regarding
the
effects
of
smoking
in
MIBC
needs
to
continue
to
improve
our
understanding
and
answer many
questions.
For
example,
E U R O P E A N
U R O L O G Y
F O C U S
1
( 2 0 1 5
)
1 7 – 2 7
21