Radical Cystectomy for Urothelial Carcinoma of the Bladder
Marc C. Smaldone
Fellow in Urologic Oncology, Fox Chase Cancer Center
for
Introduction
It has been estimated that in 2010, there were more than 70,000 new cases of
bladder cancer diagnosed in the United State, with more than 14,000 cancer specific
deaths1. While approximately 70-80% present with non muscle invasive disease, 20% of
these patients will be refractory or intolerant to intravesical therapies and another 1030% of these patients will ultimately progress to muscle invasive disease2. For patients
with NMICB that progress and the 20-30% that present with organ-confined muscle
invasive disease (≥cT2), the bladder cancer NCCN guidelines recommend radical
cystoprostatectomy with consideration for neoadjuvant chemotherapy3. Large
institutional series from centers of excellence report overall 5 year survival rates ranging
from 45-66% with perioperative mortality rates less than or equal to 3%4, 5, and
perioperative complication rates ranging from 25-57%5, 6. With surgery alone, stratified
by pathologic stage, 5 year survival rates are 66% for pT2 disease, 35% for pT3 disease,
and 27% for pT4 disease respectively7.
Role of Perioperative Chemotherapy
The role of perioperative chemotherapy has been extensively debated over the
past decade. Since a substantial proportion of patients are clinically under staged prior
to cystectomy (30-50%)8 or may have prolonged recovery courses following surgery, the
use of neoadjuvant systemic chemotherapy to eradicate micrometastases, downstage
tumor size and stage, and reduce tumor implantation during surgery9 has been
extensively investigated. In 2003, Grossman et al. randomized 307 patients withpT2-4a
urothelial carcinoma to neoadjuvant methotrexate, vinblastine, doxorubicin, and
cisplatin followed by radical cystectomy versus radical cystectomy alone, and reported
that neoadjuvant therapy increased the likelihood of eliminating residual cancer in the
final pathologic specimen and was associated with increased overall survival (46 vs. 77
months, p=0.06)10. Subsequent meta-analyses of randomized controlled trials have
demonstrated a 13% relative reduction in the risk of death as well as a 5% absolute
survival benefit in patients receiving platinum-based therapy11. These studies have also
demonstrated that complication and mortality rates after cystectomy are not negatively
impacted by administration of neoadjuvant chemotherapy12. As a result of this data,
despite concern for the overtreatment of a small proportion of patients, the NCCN
guidelines recommend neoadjuvant chemotherapy in all appropriate patients with ≥pT3
disease, with consideration for use in select patients with pT2 disease as well 3.
Adjuvant therapy, which offers the advantage of being administered in only
patients with known prognostic factors of recurrence, has shown conflicting results in
clinical trials, although a recent pooled analysis of 5 prospective trials suggests that
adjuvant therapy may positively impact overall and disease free survival13. In addition, a
meta-analysis of 6 randomized trials investigating the use of cisplatin based adjuvant
therapy suggested a 25% relative reduction in the risk of death for patients receiving
adjuvant therapy versus local therapy alone14. However, these trials were very small
with methodological flaws, and these limitations limit the clinical applicability of this
data. In addition, approximately 30% of patients suffer from peri-operative
complications that may prevent or delay the receipt of adjuvant treatment 15. Regardless
of timing of administration, utilization of chemotherapy for patients with advanced
urothelial carcinoma remains inappropriately low (11.6% total from 1993-2003), which
may be due to patients factors, lack of diffusion into community practice, and agent
specific toxicities16.
Surgical Technique
Radical cystectomy is performed for patients with muscle-invasive carcinoma of
the bladder and for some patients with recurrent T1 disease or CIS that has been
unresponsive to intravesical chemotherapy. The goal of radical cystectomy is to achieve
a surgical cure and can be performed via open or minimally invasive techniques17. On
occasion, however, the procedure may be performed as a palliative procedure when the
symptoms of the disease are severe. Due to risk of intraoperative hemorrhage all antiplatelet and anticoagulants should be stopped pre-operatively, and preoperative
imaging of the chest, abdomen, and pelvis is required to rule out the presence of
systemic disease. Extensive bowel preparation has been traditionally recommended in
the past, but in contemporary practice is reserved for continent large bowel diversions
while more mild preparations are now commonly utilized in patients undergoing ileal or
incontinent urinary diversions18. The routine use of a nasogastric tube has also been
challenged and is not required in all cases19. Per the AUA guidelines, a first or 2nd
generation Cephalosporin or a combination of an Aminoglycoside/Metronidazole or
Aztreonam/Clindamycin should be administered within one hour of induction and
continued for ≤24 hours for antibiotic prophylaxis20.
The bladder is traditionally approached through a vertical midline or transverse
pfannenstiel incision. Following mobilization of the space of Retzius, the small bowel is
anteriorly retracted. The posterior peritoneum is incised, and the ureters are divided
close to the ureterovesical junction. In cases where ureteral involvement is suspected,
frozen sections can be utilized to ensure negative margins, although the necessity of
routine use has also been questioned21. The posterior retrovesical cul-de-sac is exposed,
and the posterior peritoneum is incised to expose the plane between the bladder and
the rectum. If the patient is a candidate for a nerve sparing procedure, the
neurovascular bundles can be mobilized via either an antegrade or retrograde
approach22. The anterior dissection consists of incision of the endopelvic fascia, division
of the puboprostatic ligaments, and ligation of the dorsal vein complex. If a concomitant
urethrectomy is being performed, proximal urethral dissection is continued distally
under the pubis to facilitate perineal dissection. If a continent, orthotopic diversion is
being considered, frozen section analysis of the urethra should be performed to ensure
a negative margin. Once the vascular pedicles have been ligated and divided (superior
and inferior vesical branches of the anterior division of the internal iliac artery) and the
urethra has been divided, the specimen is removed. Often a heavy suture is utilized to
ligate the proximal urethra/prostatic apex to ensure minimal tumor spillage 23. In an
anterior exenteration in a female patient, the bladder is taken en bloc with the uterus,
ovaries, and fallopian tubes, as well as a strip of the anterior vagina to ensure adequate
staging. Vaginal sparing procedures can be performed in sexually active patients that do
not have bulky trigonal or bladder neck disease24.
A pelvic lymphadenectomy can be performed either prior to or immediately
following bladder removal. Traditionally, the limits of dissection included the
genitofemoral nerve (lateral), bifurcation of the common iliac artery (cephalad), the
endopelvic fascia (caudal), and the bladder (medial). An “extended” lymphadenectomy
includes all lymphatic tissue along the common iliac arteries to the level of the aortic
bifurcation, although some surgeons include presacral nodal packets or extend
dissection proximally along the aorta to the level of the inferior mesenteric artery23. An
extended nodal dissection has been shown to improve survival in patients with either
node negative disease as well as limited regional metastatic disease25, and its
performance has been proposed as a quality of care measure26.
The stomach, jejunum, ileum, and colon have been used to reconstruct the
urinary tract following radical cystectomy. The appropriate use of these intestinal
segments requires knowledge of their surgical anatomy, techniques of isolating
segments of intestine and reconstituting continuity of the enteric tract, the problems
and techniques of anastomosing the urinary tract to the intestine, and the complications
that occur with use of the intestine27. Although a thorough discussion is beyond the
scope of this review, reconstruction options include an incontinent conduit (from either
large or small bowel), a cutaneous continent urinary diversion (large bowel), or a
continent orthotopic diversions (from either large or small bowel). The decision to use a
specific segment of bowel is based on patient specific factors, but each segment of
bowel is prone to metabolic disturbances of varying clinical significance28. In general, an
ileal conduit incontinent urinary diversion is the simplest diversion to perform and is
associated with the fewest intra operative and post operative complications29. It is
important to avoid the use of ileum in patients with short bowel syndrome,
inflammatory bowel disease, or history of previous abdominal radiation27. In these cases
a transverse colon conduit may be preferable, or a sigmoid conduit may be utilized
when a colostomy is already planned such during pelvic exenteration. Continent
diversions, including ureterosigmoidostomy (which has fallen out of favor), cutaneous
catheterizable diversions utilizing the ileocecal valve, and orthotopic diversions in which
the “neobladder” is anastomosed to the native urethra can be considered in select
patients27. In centers of excellence, continent reconstruction has become the procedure
of choice in properly selected patients, with the caveat that patients must be
appropriately counseled regarding complication risk and potential need for future
revision procedures30.
Regardless of diversion type, the most common causes of morbidity and
mortality in the immediate perioperative period are related to either the enteric-enteric
or uretero-enteric anastmoses. For intestinal anastomoses, it is important to minimize
local spillage of enteric contents, preserve the enteric blood supply, and achieve a
watertight closure off tension, which can be achieved in a hand sewn or stapled fashion.
Factors associated with anastomotic breakdown include poor blood supply, irradiated
bowel, local sepsis/abscess from intraperitoneal spillage of enteric contents, and drains
placed in close proximity to the suture/staple line27. Uretero-intestinal anastomoses can
be performed via either a refluxing or anti-refluxing fashion. Refluxing anastomoses are
less likely to stricture, and to date it has not been established that reflux in the absence
of obstruction is associated with upper tract deterioration following lower urinary tract
reconstruction31. However, principles of successful uretero-intestinal anastomosis
include watertight mucosa-mucosa apposition in a tension free manner using fine
absorbable suture over a diversion stent to minimize urine leak. Typically the left ureter
is brought underneath the sigmoid mesentary and the anastomoses are
retroperitonealized27.
Post Operative Complications
Peri-operative mortality following radical cystectomy in modern series ranges
from 1-3%5, while peri-operative complication rates using standardized criteria (such as
the Clavien classification system32) approaches 50%6. Pulmonary complications are
common and can be minimized by early ambulation, aggressive incentive spirometry
and respiratory therapy, and early nasogastric tube removal. Post operative ambulation,
use of intermittent pneumatic compression devices, and use of pharmacologic agents
including low dose unfractionated heparin or low molecular weight heparin (in select
patients at high risk) can be utilized to reduce the risk of deep vein thrombosis and
pulmonary embolus33. Wound infections, particularly in obese patients, can be
minimized by minimal use of electrocautery and copious irrigation prior to closure.
Serious infectious complications requiring an intervention, such as abdominal or pelvic
abscess leading to sepsis, are uncommon and are most typically related to urine/enteric
anastomotic leak or unrecognized visceral injury. Gastrointestinal complications
including ileus or intestinal obstruction are among the most common post operative
adverse events reported and range both in severity and the level of treatment required.
Less common chronic complications are typically related to tissue ischemia and are
specific to the type of urinary diversion employed. Examples include stomal stenosis,
enteric fistula, ureteral stricture, bladder neck contracture, and inability to catheterize a
cutaneous continent diversion, and often require an operative or interventional
radiologic procedure to definitively manage23.
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Marc C. Smaldone, MD
Fellow in Urologic Oncology, Fox Chase Cancer Center