Anterior urethra sparing cystoprostatectomy for bladder cancer: a 10-year, single center experience

Clinical presentation, diagnosis, and pathological findings

Ultimately, a study population of 51 males with cTa-4N0-2M0 bladder cancer undergoing
anterior urethra sparing cystoprostatectomy and simultaneous urinary diversion was
eligible for analysis. The patient characteristics are summarized in Additional file
1: Table S1. The median age of the patients was 66 years (range 48–84 years). Of the
56 consecutive patients, 5 patients were excluded for the following reasons: 2 patients
had no urinary diversion caused by chronic renal failure requiring maintenance hemodialysis
among their comorbid disorders, 2 patients had undergone percutaneous ureterostomy
as urinary diversion and bone metastasis, and the another one patient was diagnosed
as having squamous cell carcinoma post-pathologically. IC and NB were selected as
the approach to urinary diversion in 25 (49.0%) and 26 (51.0%) patients, respectively.
The median follow up time was 35 months (range 4–143 months). Upon review of the final
cystoprostatectomy specimen, the presence of carcinoma in situ (CIS), non-organ confined
disease (pT3 or greater), and node-positive disease were evident in 10 (19.6%), 19
(37.3%), and 9 (17.6%) patients, respectively. A total of four patients (7.9%) demonstrated
prostatic urethral involvement. While one patient had pathological prostatic ductal
disease, three exhibited stromal involvement. There were no differences in the presence
of CIS, pathological stage, UC grade, and prostate involvement when comparing patients
undergoing IC vs. NB urinary diversion.

Perioperative outcomes and complications

The median operation time was significantly shorter for the IC group (546 min) compared
with the NB group (594 min) (P = 0.027), However, there were no statistical differences in the median blood loss
or the number of hospitalization days between these subgroups (1,500 vs. 1,700 ml
and 47 vs. 41 days in the IC group vs. NB group, respectively) (Additional file 2: Table S2). The surgical margins were tumor free for all cases.

While there was no perioperative mortality, a total of 19 (37.3%) patients experienced
perioperative complications. Both ileus and pyelonephritis occurred as the most frequent
complication in 4 (7.8%) patients each. There was no significant impact on the complication
rate and type between these subgroups (Additional file 3: Table S3).

Oncologic outcomes and recurrence rates according to the site in patients with postoperative
recurrence

Five- and 10-year RFS by Kaplan–Meier estimation in IC group vs. NB group were 45.0
and 20.3% vs. 39.3 and 19.6%, respectively (p  0.05) (Fig. 1). Similarly, the 5- and 10-year DSS were 52.7 and 32.1% vs. 39.3 and 29.5%, respectively
(p  0.05) (Fig. 2). Multivariate analysis revealed three independent prognostic factors for RFS, including
age at surgery (p = 0.03), maximum pathological tumor stage (p = 0.01), lymph node
status (p = 0.0001) and two independent prognostic factors for DSS, including age
at surgery (p = 0.006), lymph node status (p = 0.03) (Additional file 4: Table S4). None of the other factors tested proved to be of prognostic significance.
Patients with lymph node-positive disease or who were over 60 years old demonstrated
significantly worse survival and higher recurrence rates than those with no lymph
node involvement or who were under 60 years of age (p = 0.013 and 0.001 or p = 0.001
and 0.001, respectively). Recurrence developed during follow-up in 20 of the 51 patients
(39.2%), including distant recurrence of abdominopelvic lymph node, lung, bone, liver
and local recurrence of muscle, rectum, ureter and remnant urethra (Additional file
5: Table S5). A total of 9 patients (17.6%), comprised of 6 in the IC group and 3 in
the NB group presented with distant, as well as local recurrences. Remnant urethral
recurrence was identified in only one patient in the NB group (2.0%) at 57 postoperative
months, although other recurrence sites were more frequently confirmed during the
same follow-up period. There were no significant differences in the recurrence rates
according to the site in patients with postoperative recurrence between each subgroup.

Fig. 1. Actual recurrence free survival in 51 patients stratified by the type of urinary diversion.

Fig. 2. Actual disease specific survival in 51 patients stratified by the type of urinary
diversion.

Decision making regarding the urethra before and after radical cystectomy due to urothelial
carcinoma has always been controversial (Huguet 2011]). The incidence of urethral recurrence of UC after radical cystectomy has been estimated
to be as high as 10% (Freeman et al. 1994]). Significant attention has been directed toward determining appropriate patient
selection for urethral preservation and orthotopic neobladder reconstruction. It is
generally accepted that orthotopic diversion should not be performed if there is a
high risk of tumor recurrence in the retained urethra. While the pathological features
considered as potentially high risk have evolved during the last decade, with some
of these factors surgeons continue to consider prophylactic urethrectomy, thereby
precluding orthotopic diversion (Hassan et al. 2004]). These characteristics include prostatic urethral involvement in men, bladder neck
and/or vaginal wall involvement in women and CIS (Freeman et al. 1996]). By contrast, there have been few reports in which intraoperative frozen section
biopsies of the urethral margin have been used systematically and with sufficient
follow-up; although most authors currently agree that this approach would determine
whether orthotopic diversion or urethrectomy should be performed (Huguet 2011]). Kassouf et al. (2008]) reported that a positive preoperative transurethral resection prostatic urethral
biopsy did not correlate with final margin and should not exclude patients from consideration
for orthotopic urinary diversion in their study of 245 radical cystectomy specimens
for UC. There are also a few reports of remnant urethral recurrence in male patients
who had undergone the ileal conduit procedure without prophylactic urethrectomy. Based
on these reports, we hypothesized that simultaneous prophylactic urethrectomy with
radical cystoprostatectomy might not always be necessary, regardless of the type of
urinary diversion, if the urethral margin alone was negative on frozen section. In
our series, surgical margins were confirmed to be tumor free for all cases. Therefore,
prophylactic urethrectomy was not performed and the types of urinary diversion were
divided into IC and NB groups, according to the complete assessment of several factors,
including patient age, patient desire, preoperative complications, past history of
digestive disease, intraoperative findings, such as the length of the mesentery or
the presence of some adhesion. As shown in Additional file 1: Table S1, there were no significant differences in the patient background among
those patients undergoing IC vs. NB urinary diversion. As a result, the histopathological
findings in our retrospective study revealed that 4 patients (7.9%) exhibited prostatic
involvement even if the negative urethral surgical margin was confirmed intraoperatively.
However, remnant urethral recurrence was identified in only one patient (2.0%) who
interestingly exhibited no prostatic involvement.

In recent years, surgeons have begun to report case series of minimally invasive radical
cystectomy for the treatment of bladder cancer, including laparoscopic radical cystectomy
(LRC) and robot-assisted radical cystectomy (RARC), demonstrating the surgical feasibility
of these procedure with the potential of reduced blood loss and more rapid return
of bowel function and hospital discharge (Nix et al. 2010]; Challacombe et al. 2011]). LRC and RARC are increasingly performed; although open radical cystectomy (ORC)
remains the standard approach for bladder cancer (Yuh et al. 2015]; Stenzl et al. 2011]; Snow-Lisy et al. 2014]; Bochner et al. 2014]; Linder et al. 2014]). Furthermore, Tyritzis et al. (2013]) reported that outcomes after RARC with totally intracorporeal neobladder diversion
appeared satisfactory and consistent with a contemporary open series. Despite these
excellent experiences and observations, high levels of clinical evidence with respect
to the significance of urethral management, such as LRC or RARC with simultaneous
prophylactic urethrectomy, are lacking. Perineal urethrectomy has been reported to
be a complicating procedure as a consequence of the extra perineal wound, longer operation
duration and delayed ambulation, although radical cysto-urethrectomy is recommended
for every patient with bladder cancer who has a urethral tumor or a risk of urethral
reinvolvement (Elshal et al. 2011]). Under this recent trend, minimally invasive surgical techniques have achieved increasing
support and the decision making process regarding the urethra before and after cystectomy
due to bladder cancer has become an even more difficult problem.

In our study, patients with lymph node-positive disease or those who were over 60 years
old demonstrated significantly worse survival and higher recurrence rates than those
with no lymph node involvement or those who were younger than 60 years. However, there
were no statistically significant differences in perioperative outcomes, except for
the median operation time, oncologic outcomes and recurrence rates based upon the
urinary diversion approach. Remnant urethral recurrence was identified in only one
patient (2.0%). These results are similar to the previous reports (Taylor et al. 2010]; Hautmann et al. 2006]). Our data indicate that anterior urethra sparing cystoprostatectomy for bladder
cancer did not influence the incidence of remnant urethral recurrence and oncologic
clinical outcome based upon different approaches to simultaneous urinary diversion.
We believe that our study could be very useful in consideration of the significance
of simultaneous prophylactic urethrectomy with radical cystectomy, regardless of LRC,
RARC, or ORC.

Our study is limited by the retrospective, non-randomized design and by the small
number of patients. A randomized clinical trial focused on the definitive urethral
management before and after minimally invasive radical cystectomy will be necessary
in the future.