EURURO Vol. 71 No. 4

552 692

lesions likely represent the degree to which an individual
patient’s disease is of pan-urothelial character. Despite this
limitation, the strategy of performing sequential resections
of the distal ureter during RCwith the objective of converting
a positive into negative margin was found to be successful in
40–82% of the patients and has been also reported
to result in lower rates of secondary UTUC .
Taken together, as secondary UTUC occurs infrequently
and relatively late after RC, studies with a limited sample
size and short follow-up are unsuitable to demonstrate or
disprove the beneficial prognostic effect of sequentially
resecting the distal ureters in case of positive FSA. This is
because in smaller studies, the denominator (absolute
number of patients without recurrence) decreases more
significantly with prolonged follow-up compared with the
absolute number of patients (numerator) who live long
enough to develop UTUC . Nonetheless, in the
absence of robust data, a positive ureteral margin on FSA
should influence surgeons to consider reresection(s) of the
given ureter as this simple procedure may render a
considerable subset (40–82%) of patients cancer-free at
the margin . With regard to the indication for FSA,
some centers have utilized a risk-adapted approach for the
usage of FSA during RC to ensure negative margins based on
the existence and number of risk factors for ureteral
malignancy . As an alternative technique, cutting the
ureters at the crossing with the common iliac arteries,
results in a low rate of positive ureteral margins at RC (1.2%)
This practice may obviate the need of sequential
resection but necessitates a longer segment of ileum for
neobladder reconstruction .
3.2.2. Urethral frozen section analysis
Even if a prostatic urethral biopsy is positive prior to RC, it
has been shown that a negative urethral frozen section at the
time of RC results in a tumor-free urethra after a follow-up
period of 10 yr Therefore in patients scheduled for OBS,
intraoperative exclusion of malignant disease at the level of
urethral dissection should be performed before urethroin-
testinal anastomosis. This also holds true for patients with
nonorthotopic or incontinent diversions and a retained
(afunctional) urethra, particularly if prostatic urothelial
maligancy was detected prior to RC Intraoperative
FSA of the urethral margin may be helpful for the decision-
making with regards to immediate urethrectomy. However,
in contrast to ureteral FSA, there is only scarce data on the
accuracy of urethral FSA at RC. In women, a study on
85 patients reported on a 100% sensitivity and specificity of
FSA for the accurate prediction of the final urethral margin
status at RC . By contrast, a small series of 100 men
treated with RC for BC reported on a low sensitivity (33%) but
high specificity ( 99%) for urethral FSA
3.3. Can urethral FSA be replaced by bladder neck and prostatic
urethral biopsy?
3.3.1. Bladder neck biopsy in women
For women, some urologists consider a bladder neck biopsy
to be oncologically equivalent to urethral FSA . To
evaluate this further, a retrospective study analyzed out-
comes of 297 women who underwent RC with OBS for BC in
four centers between 1994 and 2011 None of them
exhibited bladder neck involvement on preoperative
assessment. After a median follow-up of 64 mo (inter-
quartile range: 25–116), 81 women developed recurrent
disease (27%) with a corresponding 15-yr recurrence-free
survival rate of 66%. Two (0.6%) women experienced
secondary malignancies in the urethra only, four (1.2%)
concomitantly in the urethra and in distant organs, and in
one (0.3%) in the urethra and in the local surgical bed. The
median time to secondary urethral malignancy was 30 mo
(total range: 8–64). Although primary tumors were located
at the trigone in 27 women (9%), none of these developed
secondary tumors. FSA was negative in six of the seven
women with urethral recurrence and only one of themhad a
positive urethral margin on permanent section. A positive
permanent urethral margin status was found in seven and
was significantly associated with secondary urethral
malignancy ( p < 0.001). No significant associations were
reported for CIS, pathologic tumor and nodal stage, and
involvement of the bladder trigone.
While these data suggest that careful preoperative
assessment of the bladder neck may obviate the need for
intraoperative FSA of urethral margins, the clinically more
important question is whether women with tumor involve-
ment of the bladder neck who still desire an OBS should be
excluded from OBS a priori. As anatomical studies have
shown that malignancy at the bladder neck is associated
with a positive final urethral margin status in only 40% of the
patients , a carefully obtained full-thickness biopsy for
intraoperative FSA of the distal urethral margin may be a
better method to exclude malignancy at the level of
dissection, particularly given the very low observed recur-
rence rate in women selected using intraoperative FSA.
Nonetheless, there is currently no data comparing the
accuracy of bladder neck biopsy and FSA of the urethra in a
head-to-head manner for predicting the final urethral
margin status as well as its impact on clinical decision-
making for concurrent urethrectomy. Therefore, it should be
emphasized that in cases of equivocal histological findings
on intraoperative FSA—denudation or atypia—obtaining
additional biopsies should be considered to lower the risk
of a positive final urethral margin on permanent section .
3.3.2. Prostatic urethral biopsy
Analyses of whole-mounted prostate sections have demon-
strated that prostatic urothelial malignancy is present in up
to 38% of cystectomy specimens . Analogous to the role
of preoperative bladder neck assessment in women, it can
be hypothesized that a prostatic urethral biopsy predicts
urethral involvement at RC. In this regard, the value of
transurethral prostatic biopsy was assessed in a recent
series of 272 patients scheduled for RC . Transurethral
resection biopsies of the prostatic urethra were performed
at the 5 o’clock position and 7 o’clock position adjacent to
the verum montanum. Malignancy in the prostatic urethra
was identified in 101 patients ( 37%). The sensitivity and
specificity of transurethral prostatic biopsy for predicting
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