EURURO Vol. 71 No. 4

554 692

extirpative surgery. Therefore, the question arises whether
prophylactic urethrectomy may provide a prognostic
benefit in those at high risk of urethral recurrence.
At RC, urethrectomy is typically a part of the procedure in
women when OBS is not planned, whereas in men there is
no conclusive evidence to support the use of prophylactic
urethrectomy routinely at the time of RC. In men, the use of
prophylactic urethrectomy at RC was investigated in a
Surveillance, Epidemiology, and End Results analysis
including 2401 men treated with RC for BC . Of these,
a total of 195 men (8.1%) underwent urethrectomy for
urethral recurrences or a malignant urethral margin as
detected by permanent histological analysis. Patients were
subdivided into two groups: immediate (within 6 wk after
RC) or delayed urethrectomy (6 wk after RC or later). As
expected, patients who underwent immediate urethrect-
omy had a higher rate of stage T4 disease compared with
those who underwent delayed urethrectomy (33% vs 16%,
p < 0.001). Performance of immediate urethrectomy did not
confer a statistically significant survival benefit compared
with delayed urethrectomy (hazard ratio = 0.775, 95%
confidence interval: 0.59–1.01, p = 0.063). Nonetheless, in
our opinion, as urethrectomy is technically easy and less
time-consuming in women, those who do not receive an
OBS should undergo concurrent urethrectomy at RC to
eliminate the risk of malignant transformation of the
remnant urethral urothelium. For patients diagnosed with
urethral CIS after OBS, while urethrectomy with conversion
to a conduit diversion remains an option, a urethra-
preserving strategy with transurethral resection followed
by adjuvant BCG instillation therapy has been reported as
well In one series, intraurethral application of
BCG in six patients with CIS resulted in complete response
in five but was ineffective in patients with papillary or
invasive tumors . There is a lack of data differentiating
between treatment options in low- and high-grade urethral
recurrences after OBS. While high-grade invasive recur-
rences in the urethra often necessitate radical surgery , it
is the authors’ opinion that patients with low-grade or Ta
recurrences can be managed initially with resection and
intraurethral instillation therapy.
3.5. Is there a rationale for implementing surveillance regimens
for secondary urothelial tumors?
Generally, patients with SUTs after RC have only a beneficial
long-term prognosis if tumors are detected in noninvasive
or early invasive stages . In line with these findings, a
growing body of evidence supports the assumption that
detection of SUTs at an asymptomatic stage is associated
with prolonged survival , which also translates into
significantly improved cancer-specific survival . There-
fore, in order to improve outcomes, it is essential to firstly
understand the impact of follow-up investigations on the
detection of SUTs. In a meta-analysis of 22 retrospective
studies, it was reported that secondary UTUCs after RC were
diagnosed by routine follow-up investigations in a total of
37% of the patients . Among these patients, tumors
were detected as a result of suspicious upper tract imaging
in 30% and positive urinary cytology in 7%. For patients
who were followed-up with cytological examinations only,
the rate was 1.8/1000 compared with 7.6/1000 for those
who also had upper urinary tract imaging during follow-up.
Thus, the incidence of secondary UTUC depends on the
modality of surveillance.
Risk factors for secondary UTUC and urethral carcinoma
are similar and reflect the propensity of the remnant
urothelium for pan-urothelial disease, for example, positive
urothelial (ureteral or urethral [including prostatic ure-
thra]) disease, CIS of the bladder, and multifocal nonmuscle
invasive disease prior to RC. As only a minority (10–20%) of
cystectomized patients exhibits (one or several of) these
risk factors it is reasonable to implement a surveillance
regimen for SUTs for this specific group of patients where
the yield of detecting SUT is increased.
3.6. How should we survey the upper tract and urethra after
radical cystectomy?
Surveillance of the upper tract and urethra after RC aims to
monitor for oncological and functional abnormalities in
order to detect them at the earliest possible stage and confer
a therapeutic benefit. The majority of patients treated for
secondary urethral malignancy after RC presents initially
with symptoms ( 57%) and only one-third due to a positive
urinary cytology, while a minority ( 10%) undergo prophy-
lactic urethrectomy . In this regard, it has been
demonstrated that the detection of asymptomatic urothe-
lial recurrences is associated with an approximately 30%
reduction in the risk of mortality (hazard ratio = 0.69, 95%
confidence interval: 0.59–0.79) .
For oncological surveillance, the intensity of follow-up
regimens should depend primarily on the time since RC and
the presence of risk factors for recurrence. Secondary
urothelial tumors develop mainly in patients with histo-
logical features of panurothelial disease at RC. Given the
rarity but clinical relevance of SUTs after RC, all patients
with histologic features of panurothelial disease should be
considered for routine surveillance irrespective of number
of risk factors. Yet, as the number of risk factors has shown
to impact on the incidence of secondary urothelial tumors
the intensity of surveillance should be based on a risk-
adapted strategy We submit that the presence of risk
factors should be an impetus to consider a more intense
follow-up regimen for the upper tract and urethra: (1)
bladder neck (in women) and prostatic urethral involve-
ment, (2) multifocality, (3) history of nonmuscle-invasive
BC, and (4) positive ureteral and/or urethral disease on
permament sections.
Follow-up investigations should be based on history,
physical examination, urinary cytology with urethral wash-
ings in case of a retained urethra, cross-sectional imaging of
the upper tract, and when indicated, urethroscopy. Of note,
by contrast to prior series , recent studies report on high
sensitivity and specificity rates of 80–82% and 85–97%,
respectively, of urinary cytology for the detection of
recurrences in the remnant urothelium after RC while urine
analyses by fluorescence in situ hybridization do not result
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