80 96
tract UC who were
treated with RC with curative
intent who
experienced DR.
We
confirmed
that
time
from
RC
to
DR
is
a
strong
predictor of
survival. Mitra
et
al
reported
that
a
time
to DR
<
12 mo
is associated with worse outcomes
in patients with
UCB
[10] .Rink
et
al
and
others
confirmed
that,
in
patients
who
experience
DR,
the median
time
from
surgery
to
DR
was
<
12 mo
[9,18].
We
also
found
that other patient-
and
treatment-related
characteristics could predict CSM. For example,
leukocytosis
is
known
to be
a
sensitive nonspecific marker of
inflamma-
tion
associated with
systemic progression
including metas-
tasis
[24] .We found that an elevatedWBC at the time of DR
is
associated with
greater mortality.
It was
previously
shown
that
higher WBC
is
associated with
shorter
time
to
CSM
in
UCB
patients
who
had
DR
in
univariable
[8,18]and
multivariable
analyses
[25].
Another
variable
associated
with CSM
is anemia
[26] .We confirmed the prognostic value
of
this
factor
that
was
also
recently
demonstrated
in
metastatic
UC
patients
[13] .We
found
that
a
lower
KPS
and
higher
American
Society
of
Anesthesiologists
scores
in
UCB patients at DR are associated with a higher
risk of CSM.
Our
findings are
in
line with other
studies
[21,27]and
imply
that
comorbidities
are
important
and
should
be
taken
into
account
for
predicting
survival
in
both
localized
and
metastatic
UCB.
Finally, we
found
that
the
administration
of salvage chemotherapywas associatedwithworse survival,
possibly
biased
by
UCB
patients
with
DR
who
received
chemotherapy
due
to more
aggressive
disease
and
a worse
prognosis.
We
then developed a multivariable model
to predict CSS
in
patients who
experienced DR
after
RC
that
consisted
of
two
factors:
the
time
to DR
and KPS.
Interestingly,
the 1-yr
risk
of
CSM
after
DR
decreased
considerably
regardless
of
KPS over
the
first 12 mo after RC. After
that
time,
the
time
to
death
remained
associated with
the
time
to
DR,
although
the
rate
of
decrease
in
survival
became
proportionally
smaller. Although we did not
find
that
the presence of VMs
was an
independent predictor of CSM as
shown
in previous
studies
[8,13,21,22],
the
time
to
DR may
be
considered
a
surrogate
for
the
burden
of
disease,
thus
suggesting
that
patients with
a
shorter
time
to
DR
had
occult metastatic
disease
that
became
clinically
evident
faster.
Apolo et al
recently developed
a model
to predict overall
survival
in
308 metastatic
UC
patients
receiving
cisplatin-
based
chemotherapy
and
compared
this
model
with
the
Bajorin
risk
model
[13] .The
final
model
included
four
variables: the presence of VM, KPS, albumin, andhemoglobin.
Similar
to
our
model,
comparison
of
both
models
to
the
patient
cohort
resulted
in
a
favorable discrimination
for
the
new
developed
model
(CCI:
0.670).
Galsky
et
al
recently
published
a
similar
pretreatment
nomogram
based
on
399
UC
patients
who
received
first-line
cisplatin-based
chemotherapy
[25].
However,
in
both
studies,
all
patients
were
receiving
a
cisplatin-based
chemotherapy
and
had
a
larger burden
of metastasis
compared with
our
study.
Nakagawa
et
al
recently
developed
a
risk
model
to
predict
survival
in
patients with DR
after RC
based
on
four
factors:
time
to DR,
symptoms of DR, number of metastatic
organs,
and
C-reactive
protein
level. However,
the
clinical
benefit
of
this
risk
stratification needs
to be
assessed using
CCI
and
larger
data
sets
(
n
= 114).
Our model
did
not
perform
very well
on
patients with
missing data
(
n
= 546). This could have various explanations
such as a selection bias because patients who were excluded
due
to missing
data were
from
a
few
specific
centers.
For
example,
patients
who
had
complete
data
(especially
laboratory
values)
may
have
been
seen
by
an
oncologist
and
therefore
represent
a different disease
spectrum
result-
ing
in
different management
such
as
a
higher
likelihood
of
receiving optimal chemotherapy. However, current methods
of risk stratification may be suboptimal underlining the need
for better tools
for guiding clinical decisionmaking that need
to be
tested
and validated
in
a
controlled phased
approach.
Our
study has
several
limitations.
First and
foremost are
limitations
inherent
in
a
lack
of
data
regarding
a
possible
delay
between
diagnosis
and
surgery
due
to
patient
preferences
and
comorbidities. We
could
not
control
for
symptoms
at
DR. We
also
could
not
adjust
for
surgeons’
preferences,
experience,
or
surgical
techniques.
A
central
pathology
review was
not
performed;
however,
all
physi-
cians
operated
at
tertiary
care
centers with
experience
in
UCB.
In
addition, we
did
not
control
for
differences
in
the
indication
for
and
protocols
of
adjuvant
and
salvage
chemotherapy.
5.
Conclusions
We
confirmed
the
prognostic
value
of
KPS
and
VMs
in
patients
with
DR
following
RC
for
UCB.
We
also
found
several
other
clinical
variables
to be
associated with worse
CSM. We developed a model
for predicting survival after DR
inclusive of
time
to DR and KPS assessed at DR.
If validated,
this model
could
help
clinical
trial
design.
Author contributions:
Shahrokh F. Shariat 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:
Kluth,
Xylinas,
Kent,
Vickers,
Shariat.
Acquisition
of
data:
Ikeda, Matsumoto,
Hagiwara,
Kikuchi,
Bing,
Gupta,
Sewell,
Konety,
Todenho¨fer,
Schwentner,
Masson-Lecomte,
Vordos,
Roghmann,
Noldus,
Razmaria,
Smith,
Comploj,
Pycha,
Rink,
Baniel,
Mano, Novara,
Aziz,
Fritsche,
Brisuda,
Bivalacqua, Gontero,
Boorjian.
Analysis
and
interpretation
of
data:
Kluth, Xylinas, Kent, Vickers,
Shariat.
Drafting
of
the manuscript:
Kluth,
Xylinas,
Kent,
Vickers,
Shariat.
Critical
revision
of
the
manuscript
for
important
intellectual
content:
Boorjian,
Rieken,
Vickers,
Shariat.
Statistical
analysis:
Kluth,
Xylinas,
Kent,
Vickers,
Shariat.
Obtaining
funding:
None.
Administrative,
technical,
or material
support:
None.
Supervision:
Vickers,
Boorjian,
Shariat.
Other
(specify): None.
Financial
disclosures:
Shahrokh
F.
Shariat
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.
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