Radical cystectomy and bladder-sparing treatments for urothelial
(transitional cell) bladder cancer - UpToDate
INTRODUCTION — Radical cystectomy and urinary diversion have been the
mainstay of treatment for muscle-invasive bladder cancer for decades and
remain the standard by which other treatments are judged. More recently, the
use of neoadjuvant cisplatin-based chemotherapy has been demonstrated
improved survival in these patients. Radical cystectomy also has a role in
carefully selected patients with non-muscle invasive disease, as well as in
patients with locally advanced or metastatic bladder cancer who achieve a major
clinical response to cisplatin-based chemotherapy.
The role of radical cystectomy as the initial treatment and its use in conjunction
with neoadjuvant chemotherapy, along with the role of alternative surgical
procedures, will be discussed here. An overview of the treatment of urothelial
bladder cancer is presented separately. (See "Overview of the management of
urothelial (transitional cell) bladder cancer".)
RADICAL CYSTECTOMY: TECHNIQUE
Cystectomy — Radical cystectomy entails removal of the bladder, adjacent
organs, and regional lymph nodes.

In males, radical cystectomy generally includes removal of the prostate,
seminal vesicles, as well as the urinary bladder. This extensive resection can
cause nerve damage that results in erectile dysfunction. (See 'Nerve-sparing
procedures' below.)

In females, removal of the uterus, cervix, ovaries, and anterior vagina is
usually performed en bloc with the bladder.
Urinary diversion — Removal of the bladder requires that the urinary flow be
redirected, which may take one of several forms.

A non-continent cutaneous diversion in which the urine flows from the
ureters through a segment of bowel (usually ileum, termed ileal conduit) to the
skin surface as a stoma, where it is collected in an external bag or other
appliance.

A cutaneous continent reservoir may be constructed to avoid the need for
an external appliance (usually using the right colon and terminal ileum). The
patient self-catheterizes him or herself at regular intervals to empty the reservoir.

For men and women wishing to avoid cutaneous urinary diversion, an
orthotopic neobladder may be formed from a segment of bowel and attached to
the urethra, enabling them to void through the urethra. Continent diversions can
greatly improve patient quality of life and self-image and increase their
acceptance of radical cystectomy.
The choice of urinary diversion is based upon patient and surgeon preference
and may be influenced by the extent of cancer and other patient-related factors.
These options and the issues involved in choosing an approach to urinary
diversion for an individual patient are discussed separately. (See "Urinary
diversion and reconstruction following cystectomy".)
Pelvic lymph node dissection — In patients who undergo radical cystectomy, the
extent of pelvic lymph node dissection is defined anatomically and often
measured by the total number of lymph nodes removed, is an important predictor
of survival in those with both positive and negative lymph nodes [1-5]. The
improved prognosis associated with increasing lymph node counts may be due to
the resection of histopathologically occult nodal metastases [6] or it may be a
surrogate for the quality of surgery. (See 'Prognosis' below.)
Accumulating evidence suggests that the standard template for pelvic lymph
node dissection (distal common iliac, obturator, hypogastric, and external iliac
nodes) is inadequate. This was illustrated by a mapping study in which 290
patients had an extended lymphadenectomy with removal of all nodal regions
distal to the aortic bifurcation and removal of retroperitoneal lymph nodes below
the inferior mesenteric artery [7]. Positive lymph nodes were identified in 28
percent of cases, of which only 25 percent had positive nodes restricted to the
standard template and 25 percent had involved nodes located outside, but not
within, the standard template.
Based upon these results, many centers have adopted an extended template
dissection to include the presacral and common iliac lymph nodes to the aortic
bifurcation and often more proximal to the origin of the inferior mesenteric artery,
in addition to the pelvic lymph nodes distal to the common iliac bifurcation.
Nerve-sparing procedures — Resection of the prostate and seminal vesicles in
conjunction with cystectomy frequently results in damage to the neurovascular
bundles, thus causing impotence. Men with good erectile function who desire to
preserve their potency after radical cystectomy may be candidates for
preservation of the cavernous nerves, similar to that performed during nervesparing radical prostatectomy. (See "Radical prostatectomy for localized prostate
cancer".)
Nerve-sparing cystectomy requires dissection close to the urinary bladder,
exposing patients to the risks of positive soft tissue surgical margins. Thus,
patient selection is critical when performing nerve-sparing cystectomy.
Contralateral, unilateral nerve-sparing may be considered in patients with
invasive tumors at the posterior, lateral, or trigonal region. Bilateral nerve-sparing
may be considered in patients with non-muscle invasive disease or invasive
tumors at the anterior wall or dome of the bladder.
With careful patient selection, local recurrence following nerve-sparing
cystectomy is reported in 3 to 5 percent of patients, which is similar to that in
comparable series of patients managed without nerve-sparing [8-10]. Erections
sufficient for intercourse are reported in 31 to 50 percent of patients within one to
two years after nerve-sparing cystectomy, with most patients requiring assistance
with phosphodiesterase-5 inhibitors such as sildenafil, vardenafil or
tadalafil [9,11,12].
Although still highly controversial, prostate-sparing radical cystectomy with
orthotopic urinary diversion has been performed in some centers for carefully
selected patients to improve postoperative urinary continence and sexual
function [13]. Continence and potency are theoretically improved with prostatesparing cystectomy as dissection near the cavernous nerves and external urinary
sphincter is avoided. Short-term functional and oncologic results have been
encouraging, although concerns persist regarding the oncologic efficacy of this
approach, based upon the substantial long-term risk of recurrent urothelial
cancer within the prostatic urethra [14], as well as the risk of subsequently
developing prostate adenocarcinoma [15-18]. Thus, this procedure should be
restricted to patients without involvement of the bladder neck or prostatic urethra,
no associated carcinoma in situ (CIS), and no evidence of prostate cancer.
Preoperatively, patients with an elevated serum prostate-specific antigen (PSA)
level or a prostate nodule should undergo transrectal ultrasound-guided prostate
biopsy to rule out the presence of coexisting prostate adenocarcinoma.
Whole mount step sectioning of the prostate in men undergoing radical
cystectomy indicates that on average 40 percent of patients have urothelial
cancer and a similar number have adenocarcinoma of the prostate. Up to one
half of these latter cancers may be clinically significant, raising the specter of
leaving potentially life-threatening cancer behind with prostate sparing
procedures.
In women, parasympathetic efferent fibers from S2-4 that travel lateral to the
vagina are responsible for vascular engorgement of the clitoris and vaginal
lubrication during intercourse. Preservation of these fibers during cystectomy
may prevent vaginal dryness and dyspareunia and maintain female sexual
function.
Laparoscopic approaches — Traditionally, radical cystectomy has been
performed with an open surgical approach. Laparoscopic or robotic radical
cystectomy has been investigated as a minimally invasive alternative, with the
potential for reduced morbidity and more rapid convalescence without
compromising oncologic efficacy.
Laparoscopic cystectomy is now being performed in many centers worldwide.
Reports from these sites have demonstrated the technical feasibility and safety of
this procedure, although extensive experience with these procedures is required
to achieve optimal results.
Available results indicate that the laparoscopic technique is associated with less
bleeding but requires a longer operative time for completion. Postoperatively,
patients regain gastrointestinal function more rapidly, and the duration of
hospitalization is shorter than with open cystectomy, though this has not been
uniformly reported.
Only short-term limited data are available from a handful of experienced centers
on the oncologic outcomes following laparoscopic cystectomy. As such, the
available evidence supports proof of concept, but rigorous quality control and
long term oncologic outcomes are necessary in order to fully evaluate the safety
and efficacy of this approach. Much larger numbers of patients with longer followup and randomized clinical trials will be required to establish therapeutic
equivalence to the gold standard of open radically cystectomy and extended
bilateral pelvic and iliac lymphadenectomy.
Minimally invasive approaches to radical cystectomy are discussed in detail
elsewhere. (See "Laparoscopic radical cystectomy".)
Complications — Patients with muscle-invasive bladder cancer typically are older
and frequently have substantial comorbidity. The median age in large series
ranges from 63 to 67 years, with approximately 5 percent over 80 years [19,20].
Furthermore, 34 to 50 percent are classified as high perioperative risk on the
basis of an American Society of Anesthesiologists score of 3 or greater (table
1) [3,21,22].
Improvements in surgical technique and perioperative care have reduced the
morbidity and mortality of radical cystectomy, although short-term complications
and perioperative mortality are reported in 28 to 57 percent and 2 to 5 percent of
patients, respectively, in single-institution and population-based studies [21-26].
The most common causes of major complications include cardiovascular
diseases, septic complications from urine or bowel leak, wound dehiscence,
pulmonary embolus, and hemorrhage. The frequency of complications appears
to be related to surgeon experience, hospital volume, age, and the presence of
medical comorbidities.
The type of urinary diversion performed and the use of neoadjuvant
chemotherapy do not significantly increase morbidity of cystectomy [27]. Despite
adding up to 60 minutes to the operative time, orthotopic urinary diversion can be
performed with acceptable rates of perioperative morbidity and mortality by
surgeons with extensive experience in radical cystectomy, including selected
patients who are elderly or have significant comorbidities [19,20,28]. (See
"Urinary diversion and reconstruction following cystectomy".)
RADICAL CYSTECTOMY: INDICATIONS AND OUTCOMES
Muscle-invasive bladder cancer
Outcomes — In patients with muscle-invasive disease, the outcomes following
radical cystectomy correlate with the extent of local invasion and with the
presence or absence of lymph node involvement (table 2) [1,8,29-32].

About 50 to 60 percent of patients with invasive bladder cancer (clinical
stage T2-T4a) have organ-confined disease without lymph node involvement
(pathologic stage pTIS-T2, pN0). In this group, long-term survival is reported in
75 to 85 percent of cases.

In 20 to 30 percent of cases, local extension into the perivesical fat (pT3a-
b) and/or adjacent pelvic viscera (pT4a) will be present in the cystectomy
specimen without lymph node disease (N0). Long-term survival in this setting is
approximately 45 to 55 percent of these patients.

In 20 to 30 percent of patients, regional lymph node metastasis (pTany,
pN1-3) is identified, and this is associated with a substantially poorer prognosis,
with 25 to 35 percent of patients remaining disease-free.
Even when radical cystectomy does not result in cure, surgery effectively controls
pelvic disease in most patients with a local recurrence rate of 6 to 9 percent
[2,8,29,30,33,34].
Neoadjuvant chemotherapy — Neoadjuvant chemotherapy followed by radical
cystectomy is now considered by many to be a standard of care for muscleinvasive bladder cancer. The rationale for this approach is based upon the high
incidence of occult systemic disease in patients who undergo cystectomy and the
high responsiveness of urothelial carcinoma of the bladder to cisplatin-based
chemotherapy.
Several randomized trials and a meta-analysis have demonstrated a survival
advantage when radical cystectomy is preceded by neoadjuvant chemotherapy,
particularly for patients with T3, T4, or node positive disease. The data
supporting this approach are discussed elsewhere. (See "Neoadjuvant
chemotherapy for urothelial (transitional cell) bladder cancer", section on
'Controlled trials'.)
Preoperative RT — Preoperative radiation therapy (RT) has not been shown to
improve the outcome of patients undergoing cystectomy and is no longer used
routinely. Although preoperative RT may eradicate disease in a small proportion
of patients who then undergo cystectomy [35,36], randomized trials did not
confirm a survival benefit compared to cystectomy alone [37-39]. In addition,
preoperative RT increases the risk of operative complications [40] and makes the
creation of an internal urinary reservoir using irradiated bowel more difficult [41].
BCG-refractory bladder cancer — In the United States, the standard approach for
high-grade, non-muscle invasive bladder cancer (Ta, T1, carcinoma in situ [CIS],
(table 2) is transurethral resection (TUR) followed by intravesical immunotherapy
with BCG. (See "Treatment of non-muscle-invasive bladder cancer", section on
'Intravesical BCG'.)
Radical cystectomy is generally recommended for patients whose disease is
refractory to BCG, because the risk of progression to muscle-invasive cancer is
80 to 100 percent. BCG-refractory disease is defined as any recurrent nonmuscle invasive disease at least six months after initiating BCG therapy, any high
grade T1 tumor at three months, or recurrence of any tumor while on
maintenance BCG therapy.
Although other intravesical agents (eg, gemcitabine, valrubicin, mitomycin)
frequently induce a complete response, long-term durable responses to salvage
intravesical therapy are achieved in only 15 to 20 percent of patients. Thus,
salvage intravesical therapy in patients with BCG-refractory disease is generally
reserved for those who are unwilling or unfit to undergo radical cystectomy.(See
"Treatment of non-muscle-invasive bladder cancer".)
High-grade non-muscle invasive disease — Immediate radical cystectomy for TaT1-Tis, high-grade bladder cancer is typically recommended only for patients with
a long life expectancy and who have multiple and/or large tumors. The rationale
for immediate cystectomy rather than BCG therapy is based upon the 50 percent
risk of progression to muscle-invasive disease and the 35 percent long-term
cancer-specific mortality with BCG [42]. The reported cancer-specific survival
associated with immediate cystectomy for these patients is 85 to 90 percent [2931].
Recurrent/persistent muscle-invasive disease — A number of strategies are used
in an attempt to preserve the bladder in selected patients with muscle-invasive
disease, including radical transurethral resection, partial cystectomy, and
chemoradiation. (See 'Bladder preservation strategies' below.)
Approximately 50 percent of these patients will experience recurrent bladder
cancer. Salvage radical cystectomy is required in those who develop a muscleinvasive recurrence.
Locally advanced bladder cancer — An estimated 10 to 20 percent of patients
with invasive bladder cancer have locally advanced, inoperable tumors, based
upon involvement of pelvic sidewall or adjacent viscera (clinical stage T4B) or
bulky nodal metastasis (N2-3).
The standard treatment for these patients is induction chemotherapy with
cisplatin-based multi-agent chemotherapy. Major clinical responses to
chemotherapy are reported in 40 to 65 percent of these patients with locally
advanced bladder cancer, making them potential candidates for postchemotherapy cystectomy. Patients with residual disease who do not undergo
cystectomy have a median survival of one to two years [43,44].
The role of salvage cystectomy in patients with a major response to
chemotherapy was illustrated by a retrospective analysis of 203 patients treated
at Memorial Sloan-Kettering Cancer Center [44]. Overall, 50 patients were
operated on for suspected residual disease following chemotherapy. Of these, 30
underwent a complete resection of all residual disease, while 17 had no viable
tumor at surgery. Three were unresectable and died of cancer. Of the 30 who
underwent salvage cystectomy, 10 (33 percent) were alive at five years. This
result was similar to the 46 patients who achieved a complete response to
chemotherapy (either by clinical criteria or surgical confirmation), 41 percent of
whom were alive at five years.
Post-chemotherapy cystectomy may be considered for carefully selected patients
with unresectable primary tumors and/or bulky regional nodal metastasis
following three to six cycles of induction chemotherapy. This procedure should be
restricted to healthy patients with a major clinical response to chemotherapy (pT0
on repeat TUR, down-staging by two or more clinical stages, 50 percent or
greater resolution without growth or new lesions for four weeks) and good
performance status.
Miscellaneous indications — Uncommon indications for radical cystectomy in
patients without muscle-invasive bladder cancer include diffuse, low-grade,
papillary bladder cancer (papillomatosis) that is not amenable to complete
transurethral resection. (See "Pathology of bladder neoplasms", section on
'Papillary lesions'.)
Radical cystectomy may also be indicated for patients with bladder cancers that
cause symptoms (eg, hemorrhage, urinary frequency) that cannot be managed
endoscopically or medically.
Prognosis — The pathologic stage of the primary tumor is among the most
important prognostic parameters. (See 'Outcomes' above.)
Other factors include:

Quality of surgery — Analyses of population-based studies and
randomized trials of patients treated in academic and community settings have
revealed wide variations in the quality of radical cystectomy and pelvic
lymphadenectomy related to surgical training and case volume [1,45].
The importance of the quality of surgery was illustrated by a secondary analysis
of factors known to be associated with prognosis in a randomized trial in which
patients with muscle invasive bladder cancer underwent radical cystectomy with
or without neoadjuvant chemotherapy [1]. The type of surgeon (fellowship-trained
urologic oncologist versus other) was a significant predictor of positive surgical
margins (4 versus 16 percent), fewer than 10 nodes removed (30 versus 63
percent), local recurrence (6 versus 23 percent), and survival at five years (58
versus 48 percent). (See 'Pelvic lymph node dissection' above.)

Extent of lymph node involvement — For patients with lymph node
metastasis, prognosis is correlated with the pathologic stage of the bladder
tumor, the presence of extranodal extension, and the number of lymph nodes
removed [46-48].
More recently, the lymph node density (the ratio of the number of positive lymph
nodes to the number of lymph nodes removed) has been reported to be an
important determinant of outcome for patients with lymph node metastasis.
Lymph node density is a composite variable of the extent of nodal metastases
and the quality and extent of the pelvic lymphadenectomy. In two large series,
patients with a lymph node density <20 percent had a five-year survival of 43 and
55 percent, respectively, while for those >20 percent the five-year survival was
15 and 17 percent [49,50].

Miscellaneous factors — A number of other factors may also influence the
prognosis following cystectomy:

Positive soft tissue surgical margins were reported in 4 to 6 percent of
patients in two large series [33,51]. In both series, the presence of positive
margins was associated with a significant decrease in five-year cancer specific
survival.

Lymphovascular invasion is an independent predictor of progression in T1
and muscle-invasive, node-negative bladder cancer in several cohorts [52-56].

Molecular markers such as p53, p21, p27kip1, pRB, and p16 are
independent predictors of post-cystectomy survival in several series [57-59];
however, seemingly contradictory data exist most notably for T1 tumors [60].
Multiple studies have suggested that panels of such markers may be better at
predicting recurrence and/or survival following initial treatment [61,62]. Such
markers are not routinely evaluated in cystectomy specimens and require further
validation before they can be recommended for routine use [63].
The probability of recurrence after cystectomy can be accurately predicted by
nomograms that consider multiple prognostic factors such as pathologic stage,
regional nodal involvement, tumor grade and histology, lymphovascular invasion,
and patient age. Such models predict recurrence more accurately than
pathologic stage alone [52,64].
BLADDER PRESERVATION STRATEGIES — The risk of perioperative
morbidity associated with radical cystectomy and the substantial impact of
urinary diversion requiring an external appliance on health-related quality-of-life
has led to the use of less radical approaches for the management of patients with
muscle-invasive bladder cancer.
For patients who are elderly or have significant comorbid illnesses and for those
who desire to preserve their bladders, alternatives to radical cystectomy include:

Radical transurethral resection (TUR)

Partial cystectomy

Radiation therapy (RT) techniques, including definitive external RT alone,
and external beam RT combined with interstitial radiation implants
(brachytherapy), and a combined modality approach using resection plus RT and
concurrent chemotherapy.
In general, bladder preservation approaches are considered by many to produce
inferior oncologic outcomes compared to radical cystectomy, although this has
not been proven in randomized trials.
Optimal candidates for these alternatives are those with solitary, muscle-invasive
tumors clinically confined to the bladder, no associated carcinoma in situ (CIS)
and no evidence of hydronephrosis. For patients who meet these criteria,
intermediate- and long-term cancer-specific survival rates approach those
achieved with radical cystectomy, and 35 to 50 percent of patients will survive
five years with an intact bladder.
Radical transurethral resection — Optimal candidates for radical transurethral
resection (TUR) are those with solitary tumors at the trigone, posterior, or lateral
walls with focal invasion into muscularis propria. Patients should have no
evidence of residual cancer on repeat TUR, and should not have any evidence of
associated CIS or prostatic urethral involvement.
The role of definitive TUR was illustrated by a retrospective series of 432 patients
with muscle invasive bladder cancer who had been referred for definitive
management [65]. Of the 151 patients who had either no evidence of cancer (T0)
or only T1 tumors following restaging TUR, 99 were treated by TUR alone and 52
underwent radical cystectomy. Of those treated by TUR alone, the 10-year
cancer-specific survival was 76 percent and 57 percent survived with their
bladders intact. These results are similar to the 71 percent 10-year cancerspecific survival in the 52 patients who were T0-T1 on restaging-TUR who
underwent immediate cystectomy.
However, radical TUR is applicable to only a small minority of patients with
muscle-invasive disease. In a series of 327 patients treated at M. D. Anderson
Cancer Center from 1997 to 2002, only 35 (11 percent) were considered eligible
for TUR followed by surveillance, and only 27 of these actually opted for
management with this approach rather than immediate cystectomy [66].
Intensive, long-term cystoscopic follow-up in these patients is mandatory
because of the risk of recurrent bladder tumors.
Partial cystectomy — Partial cystectomy is an option for carefully selected
patients. Such patients should have a solitary, muscle-invasive tumor that is
located anteriorly or at the bladder dome, in which a 2 cm margin of normal, nondistended bladder can be removed around the base of the lesion. The presence
of associated carcinoma-in-situ (CIS), prostatic urethral involvement, or a prior
history of recurrent bladder or upper tract urothelial tumors are contraindications
to partial cystectomy.
Partial cystectomy allows complete pathologic staging of the primary tumor, and
an extended pelvic lymph node dissection can be performed while preserving
urinary and sexual function and avoiding the need for urinary diversion.
The disadvantages of partial cystectomy are a midline scar, the potential for
significant blood loss, the risk of tumor recurrence in the midline scar given that
the bladder is opened during the procedure (unlike radical cystectomy), and the
risk of recurrent tumor in the residual bladder.
Long-term survival after partial cystectomy is reported in about 70 percent of
patients and 53 to 75 percent enjoyed long-term survival with their bladders intact
[67-70]. However, it is important to recognize the extreme selection bias in these
series relative to cohorts undergoing cystectomy or chemoradiation.
Although favorable outcomes have been reported in these series, strict
adherence to selection criteria is mandatory to avoid a much worse long-term
outcome.
Radiation therapy
External beam RT — Definitive external beam RT is often recommended for frail,
elderly patients or those medically unfit for other approaches in an effort to
palliate local symptoms. Local recurrence after RT alone (without concurrent
cytotoxic treatment) is reported in up to 70 percent of patients and five-year
survival ranges from 20 to 40 percent. Thus, definitive external beam RT is not
considered an acceptable alternative to radical cystectomy in otherwise healthy
patients.
Brachytherapy — In patients with a small (<5 cm) solitary, muscle-invasive
bladder tumor, brachytherapy has been combined with external beam RT to
provide a radiation boost to the primary tumor. In this highly selected population,
outcomes appear to be similar to those reported with radical cystectomy,
although equivalence has not been demonstrated in randomized trials [71,72].
Currently, this approach is
not routinely offered to patients outside of select centers.
Chemoradiation — The largest experience with bladder preservation is with
chemoradiation, which involves a sequence of treatments and assessment as
demonstrated in the clinical trials experience of the Radiation Trials Oncology
Group [73,74]:

Repeat aggressive TUR directed at leaving a minimal cancer residuum

External beam RT (45 to 50 Gy) to the pelvis

Repeat cystoscopy to assess response

If a complete response is documented (including negative random
biopsies and negative urine cytology), RT is completed with 20 to 25 Gy boost to
the bladder

If a complete response is not obtained, the patient needs to undergo
immediate radical cystectomy because the chance of long-term disease control is
extremely low
RT is given in conjunction with a chemosensitizing agent such as cisplatin, 5-FU
or paclitaxel. Approximately 60 to 75 percent of patients will achieve a complete
response to chemoradiation and preserve their bladders; the 25 to 40 percent of
non-responders will usually undergo immediate salvage cystectomy. The most
important predictor of outcome in patients undergoing chemoradiation is the
completeness of transurethral resection (TUR) prior to RT. Patients with
hydronephrosis or anemia have much less favorable outcomes.
The results with a chemoradiation approach are discussed in detail elsewhere.
(See "Multimodality approaches for bladder preservation in invasive bladder
cancer".)
Risk of recurrence — Bladder cancer is associated with a field defect of the
urinary mucosa, with the result that the entire lining of the urinary tract may be at
risk for developing malignancy. (See "Epidemiology and etiology of urothelial
(transitional cell) carcinoma of the bladder", section on 'Etiology and risk factors'.)
As a result, between 30 to 60 percent of patients who undergo bladder
preservation therapy will develop recurrent bladder tumors, approximately half of
which are invasive. Salvage radical cystectomy in this setting is associated with
overall survival rates of 40 to 50 percent, which probably represents a 10 to 20
percent reduction in survival compared to management with immediate radical
cystectomy.
POSTTREATMENT MANAGEMENT — Patients who have undergone definitive
therapy for bladder cancer are at risk for the development of distant metastases,
as well as for urothelial recurrence in the renal pelvis, ureters, or urethra.
The risk of urothelial recurrence is long-term and surveillance is discussed
elsewhere. (See "Epidemiology and etiology of urothelial (transitional cell)
carcinoma of the bladder", section on 'Etiology and risk factors' and "Treatment of
non-muscle-invasive bladder cancer", section on 'Posttreatment management'.)
The risk of developing disseminated metastases is highest in the first few years
after treatment. Frequent imaging of the chest, abdomen, and pelvis for evidence
of recurrence is recommended, along with blood chemistries [75,76]. Whether or
not early detection of disseminated disease improves survival remains uncertain
[77].
INFORMATION FOR PATIENTS — Educational materials on this topic are
available for patients. (See "Patient information: Bladder cancer treatment;
invasive cancer".) We encourage you to print or e-mail this topic review, or to
refer patients to our public web site, www.uptodate.com/patients, which includes
this and other topics.
SUMMARY AND RECOMMENDATIONS

For patients with muscle-invasive bladder cancer who are not candidates
for bladder preservation approaches, we recommend radical cystectomy (Grade
1B). (See 'Muscle-invasive bladder cancer' above.)
- For many patients with muscle-invasive bladder cancer who are able to
tolerate cisplatin-based chemotherapy, we recommend that radical cystectomy
be preceded by neoadjuvant chemotherapy (Grade 1A). Those most likely to
benefit have disease spread beyond the bladder muscle or into adjacent organs
or spread to the pelvic lymph nodes. (See "Neoadjuvant chemotherapy for
urothelial (transitional cell) bladder cancer", section on 'Neoadjuvant
chemotherapy'.)

- Radical cystectomy and neoadjuvant chemotherapy is also
recommended for patients with small cell carcinoma of the bladder.
(See "Extrapulmonary small cell cancer", section on 'Bladder ESCC'.)

For patients who do not receive neoadjuvant chemotherapy but have
perivesical tumor extension (stage T3 or higher, (table 2) or regional lymph node
involvement and who are likely to tolerate a cisplatin-based chemotherapy, we
suggest adjuvant chemotherapy (Grade 2C).
(See "Adjuvant chemotherapy for urothelial (transitional cell) carcinoma of the
bladder", section on 'Clinical results'.)

Radical cystectomy is also used for carefully selected patients with less
advanced disease. (See "Treatment of non-muscle-invasive bladder cancer",
section on 'Indications for cystectomy',:

Low-stage or non-muscle invasive tumors that have recurred despite
intravesical BCG treatment. (See 'BCG-refractory bladder cancer' above.)
- High-grade T1 (table 2) lesions that are associated with carcinoma in situ
(CIS). (See 'High-grade non-muscle invasive disease' above.)

Symptoms related to bladder pathology that cannot be managed medically
or endoscopically. (See 'Miscellaneous indications' above.)

For initially inoperable patients who were rendered completely resectable
following a major response to chemotherapy, we recommend radical cystectomy
(Grade 1B). (See 'Locally advanced bladder cancer' above.)

Radical cystectomy should include an extended pelvic lymph node
dissection and should be performed in a center with adequate expertise and
experience in this procedure (Grade 2A). (See 'Pelvic lymph node
dissection' above and 'Prognosis' above.)

Options for urinary diversion include a non-continent diversion (ileal
conduit), a continent catheterizable reservoir, or an orthotopic neobladder. The
choice should be determined by the patient and clinician, based upon a
consideration of the potential benefits, complications and side effects of each
approach. (See "Urinary diversion and reconstruction following cystectomy".)

Bladder preservation strategies are an alternative approach for carefully
selected patients. Options include chemoradiation, radical transurethral
resection, and partial cystectomy. These approaches may offer significant
advantages in terms of health-related quality of life but their equivalence in
producing long-term tumor control has not been established. (See 'Bladder
preservation strategies' above.)

Definitive radiation therapy (RT) with or without concurrent cisplatin-based
chemotherapy is an alternative for patients who are not candidates for a bladder
preservation approach and are medically unfit for cystectomy or who refuse
cystectomy. (See 'Chemoradiation' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
Herr, HW, Faulkner, JR, Grossman, HB, et al. Surgical factors influence
bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004;
22:2781.
Herr, HW. Extent of surgery and pathology evaluation has an impact on
bladder cancer outcomes after radical cystectomy. Urology 2003; 61:105.
Koppie, TM, Vickers, AJ, Vora, K, et al. Standardization of pelvic
lymphadenectomy performed at radical cystectomy: can we establish a minimum
number of lymph nodes that should be removed? Cancer 2006; 107:2368.
Dhar, NB, Klein, EA, Reuther, AM, et al. Outcome after radical cystectomy
with limited or extended pelvic lymph node dissection. J Urol 2008; 179:873.
Canter, D, Guzzo, TJ, Resnick, MJ, et al. A thorough pelvic lymph node
dissection in presence of positive margins associated with better clinical
outcomes in radical cystectomy patients. Urology 2009; 74:161.
Herr, HW, Bean, MA, Whitmore, WF Jr. Prognostic significance of regional
lymph node histology in cancer of the bladder. J Urol 1976; 115:264.
Leissner, J, Ghoneim, MA, Abol-Enein, H, et al. Extended radical
lymphadenectomy in patients with urothelial bladder cancer: results of a
prospective multicenter study. J Urol 2004; 171:139.
Madersbacher, S, Hochreiter, W, Burkhard, F, et al. Radical cystectomy
for bladder cancer today--a homogeneous series without neoadjuvant therapy. J
Clin Oncol 2003; 21:690.
Schoenberg, MP, Walsh, PC, Breazeale, DR, et al. Local recurrence and
survival following nerve sparing radical cystoprostatectomy for bladder cancer:
10-year followup. J Urol 1996; 155:490.
10.
Nieuwenhuijzen, JA, Meinhardt, W, Horenblas, S. Clinical outcomes after
sexuality preserving cystectomy and neobladder (prostate sparing cystectomy) in
44 patients. J Urol 2005; 173:1314.
11.
Kessler, TM, Burkhard, FC, Perimenis, P, et al. Attempted nerve sparing
surgery and age have a significant effect on urinary continence and erectile
function after radical cystoprostatectomy and ileal orthotopic bladder substitution.
J Urol 2004; 172:1323.
12.
Zippe, CD, Raina, R, Massanyi, EZ, et al. Sexual function after male
radical cystectomy in a sexually active population. Urology 2004; 64:682.
13.
Rozet, F, Lesur, G, Cathelineau, X, et al. Oncological evaluation of
prostate sparing cystectomy: the Montsouris long-term results. J Urol 2008;
179:2170.
14.
Herr, HW, Donat, SM. Prostatic tumor relapse in patients with superficial
bladder tumors: 15-year outcome. J Urol 1999; 161:1854.
15.
Damiano, R, Di Lorenzo, G, Cantiello, F, et al. Clinicopathologic features
of prostate adenocarcinoma incidentally discovered at the time of radical
cystectomy: an evidence-based analysis. Eur Urol 2007; 52:648.
16.
Sanli, O, Acar, O, Celtik, M, et al. Should prostate cancer status be
determined in patients undergoing radical cystoprostatectomy?. Urol Int 2006;
77:307.
17.
Abdelhady, M, Abusamra, A, Pautler, SE, et al. Clinically significant
prostate cancer found incidentally in radical cystoprostatectomy specimens. BJU
Int 2007; 99:326.
18.
Saad, M, Abdel-Rahim, M, Abol-Enein, H, Ghoneim, MA. Concomitant
pathology in the prostate in cystoprostatectomy specimens: a prospective study
and review. BJU Int 2008; 102:1544.
19.
Stroumbakis, N, Herr, HW, Cookson, MS, Fair, WR. Radical cystectomy in
the octogenarian. J Urol 1997; 158:2113.
20.
Clark, PE, Stein, JP, Groshen, SG, et al. Radical cystectomy in the
elderly: comparison of clincal outcomes between younger and older patients.
Cancer 2005; 104:36.
21.
Chang, SS, Cookson, MS, Baumgartner, RG, et al. Analysis of early
complications after radical cystectomy: results of a collaborative care pathway. J
Urol 2002; 167:2012.
22.
Cookson, MS, Chang, SS, Wells, N, et al. Complications of radical
cystectomy for nonmuscle invasive disease: comparison with muscle invasive
disease. J Urol 2003; 169:101.
23.
Knap, MM, Lundbeck, F, Overgaard, J. Early and late treatment-related
morbidity following radical cystectomy. Scand J Urol Nephrol 2004; 38:153.
24.
Hollenbeck, BK, Miller, DC, Taub, D, et al. Identifying risk factors for
potentially avoidable complications following radical cystectomy. J Urol 2005;
174:1231.
25.
Konety, BR, Allareddy, V, Herr, H. Complications after radical cystectomy:
analysis of population-based data. Urology 2006; 68:58.
26.
Novotny, V, Hakenberg, OW, Wiessner, D, et al. Perioperative
complications of radical cystectomy in a contemporary series. Eur Urol 2007;
51:397.
27.
Hall, MC, Swanson, DA, Dinney, CP. Complications of radical cystectomy:
impact of the timing of perioperative chemotherapy. Urology 1996; 47:826.
28.
Parekh, DJ, Clark, T, O'Connor, J, et al. Orthotopic neobladder following
radical cystectomy in patients with high perioperative risk and co-morbid medical
conditions. J Urol 2002; 168:2454.
29.
Stein, JP, Lieskovsky, G, Cote, R, et al. Radical cystectomy in the
treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin
Oncol 2001; 19:666.
30.
Hautmann, RE, Gschwend, JE, de Petriconi, RC, et al. Cystectomy for
transitional cell carcinoma of the bladder: results of a surgery only series in the
neobladder era. J Urol 2006; 176:486.
31.
Shariat, SF, Karakiewicz, PI, Palapattu, GS, et al. Outcomes of radical
cystectomy for transitional cell carcinoma of the bladder: a contemporary series
from the Bladder Cancer Research Consortium. J Urol 2006; 176:2414.
32.
Tilki, D, Svatek, RS, Karakiewicz, PI, et al. Characteristics and outcomes
of patients with pT4 urothelial carcinoma at radical cystectomy: a retrospective
international study of 583 patients. J Urol 2010; 183:87.
33.
Dotan, ZA, Kavanagh, K, Yossepowitch, O, et al. Positive surgical margins
in soft tissue following radical cystectomy for bladder cancer and cancer specific
survival. J Urol 2007; 178:2308.
34.
Herr, H, Lee, C, Chang, S, Lerner, S. Standardization of radical
cystectomy and pelvic lymph node dissection for bladder cancer: a collaborative
group report. J Urol 2004; 171:1823.
35.
Whitmore, WF Jr, Batata, MA, Ghoneim, MA, et al. Radical cystectomy
with or without prior irradiation in the treatment of bladder cancer. J Urol 1977;
118:184.
36.
Shipley, WU, Cummings, KB, Coombs, LJ, et al. 4,000 RAD preoperative
irradiation followed by prompt radical cystectomy for invasive bladder carcinoma:
A prospective study of patient tolerance and pathologic downstaging. J Urol
1982; 127:48.
37.
Slack, NH, Bross, ID, Prout, GR Jr. Five-year follow-up results of a
collaborative study of therapies for carcinoma of the bladder. J Surg Oncol 1977;
9:393.
38.
Smith, JA Jr, Crawford, ED, Paradelo, JC, et al. Treatment of advanced
bladder cancer with combined preoperative irradiation and radical cystectomy
versus radical cystectomy alone: a phase III intergroup study. J Urol 1997;
157:805.
39.
Huncharek, M, Muscat, J, Geschwind, JF. Planned preoperative radiation
therapy in muscle invasive bladder cancer; results of a meta-analysis. Anticancer
Res 1998; 18:1931.
40.
Reisinger, SA, Mohiuddin, M, Mulholland, SG. Combined pre- and
postoperative adjuvant radiation therapy for bladder cancer--a ten year
experience. Int J Radiat Oncol Biol Phys 1992; 24:463.
41.
Wammack, R, Wricke, C, Hohenfellner, R. Long-term results of ileocecal
continent urinary diversion in patients treated with and without previous pelvic
irradiation. J Urol 2002; 167:2058.
42.
Cookson, MS, Herr, HW, Zhang, ZF, et al. The treated natural history of
high risk superficial bladder cancer: 15-year outcome. J Urol 1997; 158:62.
43.
Prout, GR, Marshall, VF. The prognosis with untreated bladder tumors.
Cancer 1956; 9:551.
44.
Dodd, PM, McCaffrey, JA, Herr, H, et al. Outcome of postchemotherapy
surgery after treatment with methotrexate, vinblastine, doxorubicin, and cisplatin
in patients with unresectable or metastatic transitional cell carcinoma. J Clin
Oncol 1999; 17:2546.
45.
Konety, BR, Joslyn, SA, O'Donnell, MA. Extent of pelvic
lymphadenectomy and its impact on outcome in patients diagnosed with bladder
cancer: analysis of data from the Surveillance, Epidemiology and End Results
Program data base. J Urol 2003; 169:946.
46.
Fleischmann, A, Thalmann, GN, Markwalder, R, Studer, UE.
Extracapsular extension of pelvic lymph node metastases from urothelial
carcinoma of the bladder is an independent prognostic factor. J Clin Oncol 2005;
23:2358.
47.
Wright, JL, Lin, DW, Porter, MP. The association between extent of
lymphadenectomy and survival among patients with lymph node metastases
undergoing radical cystectomy. Cancer 2008; 112:2401.
48.
Hollenbeck, BK, Ye, Z, Wong, SL, et al. Hospital lymph node counts and
survival after radical cystectomy. Cancer 2008; 112:806.
49.
Kassouf, W, Agarwal, PK, Herr, HW, et al. Lymph node density is superior
to TNM nodal status in predicting disease-specific survival after radical
cystectomy for bladder cancer: analysis of pooled data from MDACC and
MSKCC. J Clin Oncol 2008; 26:121.
50.
Stein, JP, Cai, J, Groshen, S, Skinner, DG. Risk factors for patients with
pelvic lymph node metastases following radical cystectomy with en bloc pelvic
lymphadenectomy: concept of lymph node density. J Urol 2003; 170:35.
51.
Novara, G, Svatek, RS, Karakiewicz, PI, et al. Soft tissue surgical margin
status is a powerful predictor of outcomes after radical cystectomy: a multicenter
study of more than 4,400 patients. J Urol 2010; 183:2165.
52.
Karakiewicz, PI, Shariat, SF, Palapattu, GS, et al. Nomogram for
predicting disease recurrence after radical cystectomy for transitional cell
carcinoma of the bladder. J Urol 2006; 176:1354.
53.
Dinney, CP, Babkowski, RC, Antelo, M, et al. Relationship among
cystectomy, microvessel density and prognosis in stage T1 transitional cell
carcinoma of the bladder. J Urol 1998; 160:1285.
54.
Reuter, VE. Lymphovascular invasion as an independent predictor of
recurrence and survival in node-negative bladder cancer remains to be proven. J
Clin Oncol 2005; 23:6450.
55.
Kunju, LP, You, L, Zhang, Y, et al. Lymphovascular invasion of urothelial
cancer in matched transurethral bladder tumor resection and radical cystectomy
specimens. J Urol 2008; 180:1928.
56.
Canter, D, Guzzo, T, Resnick, M, et al. The presence of lymphovascular
invasion in radical cystectomy specimens from patients with urothelial carcinoma
portends a poor clinical prognosis. BJU Int 2008; 102:952.
57.
Chatterjee, SJ, Datar, R, Youssefzadeh, D, et al. Combined effects of p53,
p21, and pRb expression in the progression of bladder transitional cell
carcinoma. J Clin Oncol 2004; 22:1007.
58.
Shariat, SF, Tokunaga, H, Zhou, J, et al. p53, p21, pRB, and p16
expression predict clinical outcome in cystectomy with bladder cancer. J Clin
Oncol 2004; 22:1014.
59.
Shariat, SF, Lotan, Y, Karakiewicz, PI, et al. p53 Predictive value for pT12 N0 disease at radical cystectomy. J Urol 2009; 182:907.
60.
Dalbagni, G, Parekh, DJ, Ben-Porat, L, et al. Prospective evaluation of
p53 as a prognostic marker in T1 transitional cell carcinoma of the bladder. BJU
Int 2007; 99:281.
61.
Shariat, SF, Bolenz, C, Godoy, G, et al. Predictive value of combined
immunohistochemical markers in patients with pT1 urothelial carcinoma at radical
cystectomy. J Urol 2009; 182:78.
62.
Mitra, AP, Pagliarulo, V, Yang, D, et al. Generation of a Concise Gene
Panel for Outcome Prediction in Urinary Bladder Cancer. J Clin Oncol 2009;
27:3929.
63.
Goebell, PJ, Groshen, SL, Schmitz-Drager, BJ. Guidelines for
development of diagnostic markers in bladder cancer. World J Urol 2008; 26:5.
64.
Bochner, BH, Kattan, MW, Vora, KC. Postoperative nomogram predicting
risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol 2006;
24:3967.
65.
Herr, HW. Transurethral resection of muscle-invasive bladder cancer: 10year outcome. J Clin Oncol 2001; 19:89.
66.
Leibovici, D, Kassouf, W, Pisters, LL, et al. Organ preservation for muscleinvasive bladder cancer by transurethral resection. Urology 2007; 70:473.
67.
Holzbeierlein, JM, Lopez-Corona, E, Bochner, BH, et al. Partial
cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer
Center experience and recommendations for patient selection. J Urol 2004;
172:878.
68.
Smaldone, MC, Jacobs, BL, Smaldone, AM, Hrebinko, RL Jr. Long-term
results of selective partial cystectomy for invasive urothelial bladder carcinoma.
Urology 2008; 72:613.
69.
Kassouf, W, Swanson, D, Kamat, AM, et al. Partial cystectomy for muscle
invasive urothelial carcinoma of the bladder: a contemporary review of the M. D.
Anderson Cancer Center experience. J Urol 2006; 175:2058.
70.
Capitanio, U, Isbarn, H, Shariat, SF, et al. partial cystectomy does not
undermine cancer control in appropriately selected patients with urothelial
carcinoma of the bladder: a population-based matched analysist. Urology 2009;
74:858.
71.
van der Steen-Banasik, E, Ploeg, M, Witjes, JA, et al. Brachytherapy
versus cystectomy in solitary bladder cancer: a case control, multicentre, EastNetherlands study. Radiother Oncol 2009; 93:352.
72.
Blank, LE, Koedooder, K, van Os, R, et al. Results of bladder-conserving
treatment, consisting of brachytherapy combined with limited surgery and
external beam radiotherapy, for patients with solitary T1-T3 bladder tumors less
than 5 cm in diameter. Int J Radiat Oncol Biol Phys 2007; 69:454.
73.
Shipley, WU, Kaufman, DS, Zehr, E, et al. Selective bladder preservation
by combined modality protocol treatment: Long-term outcomes of 190 patients
with invasive bladder cancer. Urology 2002; 60:62.
74.
Shipley, WU, Winter, KA, Kaufman, DS, et al. Phase III trial of
neoadjuvant chemotherapy in patients with invasive bladder cancer treated with
selective bladder preservation by combined radiation therapy and chemotherapy:
Initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol 1998;
16:3576.
75.
Bochner, BH, Montie, JE, Lee, CT. Follow-up strategies and management
of recurrence in urologic oncology bladder cancer: invasive bladder cancer. Urol
Clin North Am 2003; 30:777.
76.
Malkowicz, SB, van Poppel, H, Mickisch, G, et al. Muscle-invasive
urothelial carcinoma of the bladder. Urology 2007; 69:3.
77.
Volkmer, BG, Kuefer, R, Bartsch, GC Jr, et al. Oncological followup after
radical cystectomy for bladder cancer-is there any benefit?. J Urol 2009;
181:1587.
© 2010 UpToDate, Inc. All