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## Complete Summary

#### GUIDELINE TITLE

Pretreatment staging of invasive bladder cancer.

#### BIBLIOGRAPHIC SOURCE(S)

Jafri SZ, Dinan D, Francis IR, Baumgarten DA, Bluth EI, Bush WH Jr.,
Casalino DD, Curry NS, Israel GM, Kawashima A, Papanicolaou N, Remer EM,
Sandler CM, Spring DB, Fulgham P, Expert Panel on Urologic Imaging.
Pretreatment staging of invasive bladder cancer. \[online publication\].
Reston (VA): American College of Radiology (ACR); 2007. 8 p. \[61
references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

It updates a previous published version: Jafri SZ, Shetty M, Choyke PL,
Bluth EI, Bush WH Jr, Casalino DD, Francis IR, Kawashima A, Papanicolaou
N, Rosenfield AT, Sandler CM, Segal AJ, Tempany C, Resnick MI, Expert
Panel on Urologic Imaging. Pretreatment staging of invasive bladder
cancer. \[online publication\]. Reston (VA): American College of
Radiology (ACR); 2005. 8 p. \[51 references\]

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [May 23, 2007, Gadolinium-based Contrast
    Agents](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Gadolinium):
    The addition of a boxed warning and new warnings about the risk of
    nephrogenic systemic fibrosis (NSF) to the full prescribing
    information for all gadolinium-based contrast agents (GBCAs).

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Invasive bladder cancer

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Screening

#### CLINICAL SPECIALTY

Family Practice\
Internal Medicine\
Nuclear Medicine\
Oncology\
Radiation Oncology\
Radiology\
Urology

#### INTENDED USERS

Health Plans\
Hospitals\
Managed Care Organizations\
Physicians\
Utilization Management

#### GUIDELINE OBJECTIVE(S)

To evaluate the appropriateness of radiologic procedures for
pretreatment staging of invasive bladder cancer

#### TARGET POPULATION

Patients with invasive bladder cancer

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  X-ray

    -   Chest

    -   Radiographic survey of the whole body

    -   Intravenous urography

2.  Magnetic resonance imaging (MRI)

    -   Abdomen

    -   Pelvis

    -   Cystography

3.  Computed tomography (CT)

    -   Urography

    -   Abdomen and pelvis with contrast

    -   Chest

    -   Cystography

    -   Virtual cystoscopy

4.  Nuclear medicine (NUC), bone scan whole body

5.  fluorodeoxyglucose positron emission tomography (FDG-PET), whole
    body

6.  Ultrasound (US), bladder

    -   Transabdominal

    -   Transrectal

    -   Endoluminal and transurethral

#### MAJOR OUTCOMES CONSIDERED

Utility of radiologic procedures in post-treatment follow-up of prostate
cancer

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The guideline developer performed literature searches of peer-reviewed
medical journals, and the major applicable articles were identified and
collected.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Not Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not stated

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

One or two topic leaders within a panel assume the responsibility of
developing an evidence table for each clinical condition, based on
analysis of the current literature. These tables serve as a basis for
developing a narrative specific to each clinical condition.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus (Delphi)

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Since data available from existing scientific studies are usually
insufficient for meta-analysis, broad-based consensus techniques are
needed for reaching agreement in the formulation of the appropriateness
criteria. The American College of Radiology (ACR) Appropriateness
Criteria panels use a modified Delphi technique to arrive at consensus.
Serial surveys are conducted by distributing questionnaires to
consolidate expert opinions within each panel. These questionnaires are
distributed to the participants along with the evidence table and
narrative as developed by the topic leader(s). Questionnaires are
completed by participants in their own professional setting without
influence of the other members. Voting is conducted using a scoring
system from 1-9, indicating the least to the most appropriate imaging
examination or therapeutic procedure. The survey results are collected,
tabulated in anonymous fashion, and redistributed after each round. A
maximum of three rounds is conducted and opinions are unified to the
highest degree possible. Eighty percent agreement is considered a
consensus. This modified Delphi technique enables individual, unbiased
expression, is economical, easy to understand, and relatively simple to
conduct.

If consensus cannot be reached by the Delphi technique, the panel is
convened and group consensus techniques are utilized. The strengths and
weaknesses of each test or procedure are discussed and consensus reached
whenever possible. If \"No consensus\" appears in the rating column,
reasons for this decision are added to the comment sections.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Criteria developed by the Expert Panels are reviewed by the American
College of Radiology (ACR) Committee on Appropriateness Criteria.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**ACR Appropriateness Criteria®**

**Clinical Condition: Pretreatment Staging of Invasive Bladder Cancer**

  -----------------------------------------------------------------------------------
  **Radiologic          **Rating**   **Comments**                      **RRL\***
  Procedure**                                                          
  --------------------- ------------ --------------------------------- --------------
  X-ray chest           9            Effective screen of site of most  Min
                                     common hematogenous metastasis.   

  CT urography          8            Pre- and post-contrast with       Med
                                     excretory phase.                  

  MRI pelvis            8            See comments regarding contrast   None
                                     in text under \"Anticipated       
                                     Expectations.\"                   

  X-ray intravenous     5                                              Low
  urography                                                            

  CT abdomen and pelvis 5            May be appropriate if done in     High
  with contrast                      combination with IVU.             

  NUC bone scan whole   3            Probably not indicated unless     Med
  body                               bone pain is present.             

  MRI abdomen           3            Probably not indicated unless CT  None
                                     is inconclusive or in patients    
                                     with renal failure.               

  CT chest              3            Probably not indicated unless     Med
                                     chest radiograph is suspicious.   

  US bladder            3            Limited visualization beyond the  None
  transabdominal                     bladder wall.                     

  FDG-PET whole body    2                                              High

  US bladder            2                                              None
  transrectal                                                          

  CT cystography        2                                              High

  MRI cystography       2                                              None

  CT virtual cystoscopy 2                                              High

  X-ray radiographic    1                                              Low
  survey whole body                                                    

  US bladder            1                                              None
  endoluminal and                                                      
  transurethral                                                        

  **[Rating                                                            **\*Relative
  Scale]{.underline}:                                                  Radiation
  1=Least appropriate,                                                 Level**
  9=Most appropriate**                                                 
  -----------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Summary of Literature Review**

In 2006, an estimated 61,420 new cases of bladder cancer will occur in
the U.S., and 13,600 will die of the disease. The lifetime probability
of developing invasive bladder cancer is 1 in 28 for men and 1 in 88 for
women in the U.S. Bladder cancer has a high tendency toward
multifocality at presentation and at recurrence after treatment.
Transitional cell carcinoma of the bladder (TCCB) is the most common
cell type, accounting for greater than 90% of all cases of bladder
cancer. The average age of patients with TCCB in the U.S. is 65 at
diagnosis. Almost 80% of patients with TCCB present with hematuria,
which is either gross or microscopic and is usually painless and
intermittent.

TCCB spreads by local extension through the basement membrane into the
muscular layer, then to the perivesical fat. Progressive extension into
the muscular layer allows vascular and lymphatic invasion and more
distant spread. The most common sites of hematogenous spread are lung,
bone, liver, and brain. Superficial lesions do not metastasize until
they invade deeply and may remain indolent for many years. 70% to 85% of
TCCB is superficial at presentation, confined to the mucosa or
submucosa, without muscle invasion. Only invasive tumors will be
considered here. The imaging workup begins after the bladder tumor has
been identified cystoscopically and has been proven by biopsy.

TCCB is staged by its extension at presentation and graded I-IV
according to microscopic (pathologic) criteria of aggressiveness. The
standard staging systems for bladder cancer are the Jewett Strong
Marshall (JSM) system and the Tumor Node Metastasis (TNM) system. In the
classic JSM staging system, stage A tumors are confined to the lamina
propria, while stage B involves the muscularis propria. Stage B is
divided into superficial and deep infiltration of the muscularis.
Extension of tumor beyond the serosa is stage C, and stage D is
characterized by involvement of regional then distant nodes or other
organ involvement. The division of stage B into superficial and deep is
based on Jewett\'s observation of an 80% 5-year survival rate for
patients with B1 lesions compared with 8% for patients with B2 lesions
in a small series. The TNM system, which is now being used more
commonly, encompasses the status of the primary tumor (T), the lymph
nodes (N), and any metastasis (M) (see Appendix I in the original
guideline document).

Tumor grade relates directly to depth of invasion but inversely to
curability, so that the 5-year survival rate of patients with grade III
and IV superficial tumors is only half that of patients with low-grade I
and II superficial tumors (37% vs. 71%). Patients with invasive tumors
with no nodal involvement have a 5-year survival rate of 28%, and those
with nodal involvement have a 5-year survival rate of 11%.

Treatment ranges from cystoscopic local excision or segmental bladder
resection with pelvic lymphadenectomy for early tumors to irradiation,
chemotherapy, and/or radical extirpation for deep invasion. Radical
cystectomy with pelvic lymphadenectomy remains the standard treatment
for muscle-invasive urothelial tumors of the bladder.

Since clinical staging by cystoscopy and bimanual examination under
anesthesia is inaccurate in more than 50% of patients, imaging is vital
to the proper treatment of these patients. The principal task is to
identify extravesical spread. Unfortunately, none of the imaging
modalities can identify microscopic spread to muscle layer, perivesical
fat, lymph nodes, or other organs.

Cystography, pelvic angiography, lymphangiography (LAG) with or without
percutaneous fine-needle aspiration (FNA) biopsy, and plain-film
whole-lung laminography are no longer routinely used in staging TCCB
since the advent of cross-sectional imaging.

**Plain-Film Skeletal Survey**

Because plain-film skeletal survey sensitivity is so low, in the range
of 17% to 60%, it is also no longer used. Plain film exam is only useful
at a site of increased activity on radionuclide bone scan or local bone
pain.

**Intravenous Pyelography**

Intravenous pyelography (IVP) was once the best screening exam for
upper-tract disease and was the most sensitive test in detecting small
urothelial lesions. With widespread use of CT urography, the role of IVP
in evaluating the renal collecting system and ureter is declining.
Although only 60% of known bladder tumors are visualized by IVP,
obstruction of a ureteral orifice at the level of the ureterovesical
junction is usually due to invasive bladder tumor, if urolithiasis is
excluded. Any degree of ureteric obstruction is significantly associated
with both decreased overall survival rates and decreased tumor-free
interval. Ureteral obstruction can be demonstrated by CT urography.

One group of investigators found synchronous TCC above the bladder in 14
of 597 (2.3%) patients with TCCB, 8 (1.3%) with ureteral TCC, and 6
(1.0%) with renal TCC. They reported a range of incidence of synchronous
upper-tract lesions between 0% and 6.4% and stated that IVP \"must be
performed\" when TCCB is first diagnosed. Retrograde ureteropyelography
is also excellent for detailed study of the urothelium, especially when
IVP is contraindicated or the results are equivocal. However, recent
studies have reported an incidence of 1.1% in which IVP was able to
diagnose only 66% of cases.

**Chest Radiograph and Computed Tomography**

All patients with invasive TCCB need pulmonary evaluation. The chest
radiograph is an effective, inexpensive, low-morbidity screen. Patients
with equivocal chest radiograph and those thought to be at high risk
should have standard chest computed tomography (CT).

**Radionuclide Bone Scan**

Radionuclide skeletal scintigraphy has a sensitivity ranging from 69% to
100% but is highly nonspecific. Solitary bone lesions in patients with
underlying primary malignancies are due to metastases in only 55% of
cases. The incidence of bone metastases in bladder cancer patients
increases with tumor stage at time of diagnosis, from 5% of patients
with early-stage invasive tumors to 15% of patients with locally
advanced disease. A 4.6% positive rate was found in 458 bone scan
studies. Since therapy was affected in only 0.9%, the conclusion was
that scintigraphy has \"no place in the routine preoperative staging of
bladder carcinoma.\" Bone scanning may be limited to patients with bone
pain and/or elevated levels of serum alkaline phosphatase. Further
evaluation with plain films and/or magnetic resonance imaging (MRI) can
be helpful, and, if necessary, guided needle biopsy can be definitive.

**Ultrasound: Transabdominal, Transrectal, and Transurethral**

The distended bladder is a superb acoustic window. Size and location of
the tumor affect detectability with ultrasound (US). Lesions smaller
than 0.5 cm that are flat and/or near the bladder neck can be easily
missed. Nevertheless, detection rates of over 95% are reported. US is
limited in visualization beyond the bladder wall and cannot detect nodal
enlargement. Also it cannot differentiate wall edema, prominent mural
folds, postoperative changes, blood clots, or benign masses. Color
Doppler with transrectal ultrasound (TRUS) adds nothing to evaluation of
stage or grade.

TRUS is excellent for evaluating prostate and seminal vesicles.
Transurethral ultrasound (TUUS) is more sensitive than transabdominal
ultrasound (TAUS), and TRUS and is more accurate in staging depth of
wall involvement but is not widely available. TRUS provides local
staging information with 62% to 100% accuracy, highest for superficial
tumors. TRUS staging is unreliable for tumors larger than 3 cm and
tumors with calcifications, largely because of acoustic shadowing. It is
poor (70%) for evaluating extravesical spread. Three-dimensional US
rendering is yet another new diagnostic tool with potential to aid in
discriminating superficial from muscle-invasive tumors.

Endoluminal ultrasound (ELUS), also known as intravesical ultrasound
(IVUS), uses a miniature, high-frequency transducer introduced by a
rigid cystoscope for intravesical evaluation. ELUS is both sensitive and
specific in detecting muscle invasion in bladder cancer, with rates
comparable to those of TUUS, and it provides greater bladder wall
detail. Limitations include difficulty in depicting the tumor base in
certain locations and in depicting the depth of invasion in tumors
larger than 2 cm with broad bases.

With progression from TAUS to TRUS to TUUS and ELUS, the diagnostic
accuracy of US has improved. In 214 new cases of TCCB with pathological
correlation, one study reported overall accuracy of 78.6% in local
staging with TAUS. They had 9.8% overstaging and 11.7% understaging.
Their accuracy was 87% for stage A, 60.5% for stage B, 41.2% for stage
C, and 83.3% for stage D. Another study reported an overall accuracy of
96.5% in diagnosing and staging bladder tumors with TUUS in 104
patients: 96.2% in stage Ta-T1 lesions, 100.0% in T2 lesions, 91.7% in
T3 lesions, and 100.0% in T4 lesions. There was no discussion of N or M
staging.

Studies have shown ELUS to be 100% sensitive, 75% specific, and 84%
accurate in detecting muscle invasion in bladder cancer, with both a
positive and negative predictive value of 100%. 3-D rendering had a 66%
staging accuracy for pTa tumors, 83% for pT1 tumors, and 100% for \>pT1
or muscle invasive tumors.

**Computed Tomography of the Pelvis and Abdomen**

The primary contribution of conventional CT is distinguishing tumors
that are organ-confined from those with extravesical extension. It
demonstrates bulky thickening of the bladder wall, perivesical
extension, lymph node enlargement, and distant metastases very well.
Identification of the primary lesion can be difficult in the areas of
the bladder neck and dome. CT cannot distinguish inflammatory
postoperative or postradiation edema or fibrosis from tumor and cannot
assess depth of invasion of the bladder wall. CT is also unable to
detect microscopic or small-volume extravesical tumor extension and
metastases in nonenlarged lymph nodes.

One group of investigators found an accuracy of 50% in CT staging of
pT2(B1) and pT3a(B2) (*p*=pathologic) lesions, understaging of 29.5% of
cases, and overstaging of 20.5% of cases. Staging of pT3b(C) lesions was
46.2% accurate, with 53.8% understaged. Of 16 pT4 lesions, one (6.3%)
was correctly diagnosed and 15 were understaged. All had infiltration
into prostate or seminal vesicle.

Another study reviewed 437 cases in the literature using CT to stage
TCCB. Overall accuracy ranged from 40% to 85%, with correct staging of
nodes and metastases ranging from 82% to 97%. For extravesical
extension, accuracy ranged from 40% to 92% with a mean of 74%. Another
group found overall accuracy of 54.9%, with 39% understaging and 20.7%
false negative for extravesical spread. Preoperative CT staging altered
planned surgical management in only 3.7% of cases. Multi-detector row
helical CT with IV contrast and 60-second delayed images is a highly
sensitive and specific method for detecting bladder cancer and
associated perivesical invasion, particularly when there is a greater
than 7-day time interval between intervention and CT. Its sensitivity
and specificity are up to 92% and 98% in this setting, respectively.

Various methods for bladder distension have been studied to increase the
accuracy of detecting muscle invasion in bladder cancer on CT imaging.
These include evaluating the bladder filled with urine, urine opacified
with iodinated contrast material, and air. These methods have accuracies
of approximately 84%, 89% and 93% respectively, with overstaging and
understaging percentages comparable, ranging from 4% to 7% for
overstaging and 2% to 4% for understaging.

In addition to conventional CT, helical CT with multiplanar reformation
(MPR), 3-D reconstruction (3DR), and virtual cystoscopy (CTVC) have also
been described in the literature. Using helical CT and MPR, one group of
investigators found an overall accuracy of 87.7% in CT staging of all
stages of bladder cancer and, more specifically, 76.9% for Ta--T2
lesions and 94.7% for T3--T4 lesions. Pathologic lymph nodes were
confirmed in six of seven cases. MPR was shown to be useful in
evaluating the origin and extent of extravesical invasion, as well as
tumor relationship to the ureter. A study by another group found that
the sensitivity of 3DR in detecting bladder carcinomas of all stages was
76.9%. CT cystography and virtual cystoscopy may find use in patients
unable to tolerate traditional cystoscopy, in those for whom traditional
cystoscopy failed, or in those with narrow-necked bladder diverticula
that may contain lesions. Sensitivity for identifying 0.5 mm masses has
been reported to be 100%, and for all patients\' sensitivities of 95% in
detecting neoplasm with an accuracy of 88% have been reported with CT
cystography. Virtual cystoscopy provides comparable views to traditional
cystoscopy but may not add additional diagnostic data in patients able
to tolerate traditional cystoscopy.

Multidetector CT urography provides collecting system opacification
comparable to that of IVP.

A recent 200-patient study conducted at a fast-track hematuria clinic
demonstrated 93% sensitivity and 99% specificity for bladder cancer
detection by CT urography, rates similar to those of traditional
cystoscopy. As upper tracts are increasingly evaluated by CT for
hematuria, the addition of lower-track evaluation adds negligible cost
and avoids the discomfort that may be associated with traditional
cystoscopy, thereby streamlining the evaluation of patients with
hematuria.

Absolute degree of contrast enhancement of tumor may correlate with
histologic grade in bladder transitional cell carcinoma, as demonstrated
in a study of 65 patients. Although interesting, this finding may find
greater application in research of tumor angiogenesis and regression
post antiangiogenesis therapy.

**Magnetic Resonance Imaging**

Magnetic resonance imaging (MRI) is superior to CT in demonstrating the
lower pelvic anatomy. There is striking inherent contrast between the
bright perivesical fat and the intermediate-signal-intensity bladder
wall on T1-weighted images. Multiplanar imaging and gadolinium
enhancement improve visualization of tumors on T1-weighted images. Fat
suppression techniques can help identify perivesical extension.
Deep-muscle invasion presents as disruption of the low-signal-intensity
bladder wall by tumor, which usually is of higher signal intensity.
After intravenous gadolinium chelates, TCCB shows earlier and greater
enhancement than normal bladder or nonmalignant tissue.

Most recently, one group of investigators demonstrated staging
accuracies of 85% and 82% in differentiating superficial from muscle
invasive tumors and organ-confined from non-organ-confined tumors,
respectively. Additionally, the accuracy of pathologic lymph node
detection was 96%. Overstaging occurred in 32% of cases. The length of
time elapsed between transurethral resection and MRI did not affect
staging accuracy. Another study reviewed 340 cases using MRI. The T
staging of tumor was accurate in 73%--96% of cases, and the staging of
nodes and metastases was accurate in 73% to 98% of cases. The best
staging results were with gadolinium-enhanced T1-weighted fast spin-echo
sequences 14 seconds after injection. These authors suggest that
following cystoscopic identification of tumor, MRI should be used as the
initial imaging modality to stage the tumor. Another group of
researchers reviewed 71 patients using gadolinium-enhanced endorectal
surface coil and reported an 83% overall staging accuracy. Muscle
invasion was diagnosed with 87% accuracy, 91% sensitivity, and 87%
specificity. Another study found that MRI performed with ferumoxtran-10
(ultrasmall superparamagnetic iron oxide) contrast demonstrated an
accuracy in pathologic lymph node detection of up to 92% and a
sensitivity of up to 96%.

As with CT cystography and virtual cystoscopy, there has been interest
in MR cystography (including multiplanar reconstructions and virtual
cystoscopy) as a replacement for traditional cystoscopy and to assist in
staging. High diagnostic accuracy has been demonstrated, with
sensitivity of 90.7% and specificity of 94.0% using combined virtual
cystoscopy and multiplanar reconstructions. These results are comparable
to those of CT, and MR cystography is especially promising in special
cases where traditional cystoscopy may be contraindicated (urethral
stricture), or suboptimal (narrow-necked bladder diverticula). Similar
conclusions were previously drawn by one group of investigators.

**Computed Tomography versus Magnetic Resonance Imaging**

Noting that MRI appears to have slightly better sensitivity and
specificity than CT, one group of researchers felt that its benefits
were offset by its increased cost and the length of exam. They limited
their use of MRI to equivocal cases. Another group felt that use of CT
and MRI may be limited to tumors larger than 5 cm and to solid rather
than papillary lesions. Another study stated that MRI and CT have
similar accuracy for detecting perivesical fat invasion and that the
most notable advantage of MRI is its apparent ability to differentiate
between superficial and deep invasion of the bladder wall. Another group
concluded that MRI is the best technique for staging invasive tumors, as
it was slightly better than or equal to CT at differentiating T3a from
T3b lesions and superior to CT for tumors at the bladder dome or base.
In deeply infiltrating tumors (stages T3b-T4b), they asserted that MRI
\"is generally agreed to be the most accurate staging technique,\" and
\"when MRI is available, CT is no longer needed.\" Recently, one
investigator in a review article stated that MRI is the investigation of
choice for local staging and is the preferred technique in
postcystectomy and radiation therapy follow-up. Another group in a
review of 143 patients prior to radiotherapy confirmed that MRI is
superior to clinical staging and provided additional prognostic
information.

Both CT and MRI rely on enlargement of lymph nodes as a criterion for
metastasis, but they are limited in detecting metastases to normal-sized
nodes. This may change as further studies may corroborate the early
results of using lymphotropic nanoparticle-enhanced MRI for detecting
micrometastasis in nonenlarged lymph nodes. Lymph node metastasis in
patients with superficial tumors (less than T3) is rare, but if deep
muscle layers are involved (T2b) or if extravesical invasion is seen,
the incidence of lymph node metastasis rises to 20% to 30% and 50% to
60%, respectively. If a lymph node is considered to contain metastasis,
a fine-needle aspiration (FNA) biopsy should be considered. Both CT and
MRI are equivalent in their ability to detect nodal enlargement.

**Positron Emission Tomography and Radioimmunoscintigraphy**

Conventional positron emission tomography (PET) using
^18^F-fluorodeoxyglucose (FDG) is unsuitable for imaging bladder tumors
because of its high urinary excretion, although it may have a role in
detection of recurrent or metastatic disease. FDG-PET is 67% sensitive,
86% specific, and 80% accurate in detecting pathologic lymph nodes in
patients with bladder cancer, which exceeds both CT and MRI. A study
correlating FDG-PET and CT results in the same patients reported
sensitivity, specificity, and accuracy of 60%, 88%, and 78%,
respectively, in nodal and metastasis staging, suggesting improved
distant metastatic and locoregional node staging. ^11^C-choline PET when
compared with CT promises slightly increased accuracy of lymph node
staging (63.0% vs. 88.9%, *p*\<0.01) and may avoid false positive
results for lymph nodes due to reactive hyperplasia when compared with
CT, although further evaluation with this agent is needed to confirm
these findings.

The experimental modality of radioimmunoscintigraphy using anti-MUC1
mucin monoclonal antibody C595 labeled with various radiotracers has
been shown to be up to 90% sensitive in detecting invasive cancer and
88% sensitive in detecting distant metastases in sites such as lymph
node, bone, and lung.

**Recommendations**

With the increasingly widespread use of CT urography, the role of IVP is
declining. CT urography not only is effective for local staging but also
provides concomitant evaluation of the liver as well as nodal status.
Chest CT can be limited to those with equivocal chest radiographs.
Radionuclide bone scan is not indicated without bone pain and/or
elevated serum alkaline phosphatase levels. Plain films can be limited
to sites of increased uptake and/or bone pain. US is useful for local
tumor (T) staging; TUUS and ELUS appear to be equally effective in this
regard. Contrast-enhanced MRI is preferred over CT for local staging and
is equivalent in assessing regional lymph nodes. CT or MR virtual
cystoscopy may be used in specific cases such as evaluation of
narrow-necked bladder diverticula, which may be poorly evaluated by
traditional cystoscopy, but they are not indicated in the majority of
patients. CT and MR virtual cystoscopic techniques may also be of use in
those unable to tolerate traditional cystoscopy and may be considered to
streamline evaluation of hematuria, combining staging and screening. MRI
of the head is needed only if neurological symptoms are present. PET
studies to date are not proven to enhance pretreatment staging and are
not indicated until further validation and studies are completed.

**Anticipated Exceptions**

Nephrogenic systemic fibrosis (NSF, also known as nephrogenic fibrosing
dermopathy) was first identified in 1997 and has recently generated
substantial concern among radiologists, referring doctors and lay
people. Until the last few years, gadolinium-based MR contrast agents
were widely believed to be almost universally well tolerated, extremely
safe and non-nephrotoxic, even when used in patients with impaired renal
function. All available experience suggests that these agents remain
generally very safe, but recently some patients with renal failure who
have been exposed to gadolinium contrast agents (the percentage is
unclear) have developed NSF, a syndrome that can be fatal. Further
studies are necessary to determine what the exact relationships are
between gadolinium-containing contrast agents, their specific components
and stoichiometry, patient renal function and NSF. Current theory links
the development of NSF to the administration of relatively high doses
(e.g., \>0.2 mM/kg) and to agents in which the gadolinium is least
strongly chelated. The FDA has recently issued a \"black box\" warning
concerning these contrast agents
(<http://www.fda.gov/cder/drug/InfoSheets/HCP/gcca_200705HCP.pdf>). This
warning recommends that, until further information is available,
gadolinium contrast agents should not be administered to patients with
either acute or significant chronic kidney disease (estimated GFR \<30
mL/min/1.73m^2^), recent liver or kidney transplant or hepato-renal
syndrome, unless a risk-benefit assessment suggests that the benefit of
administration in the particular patient clearly outweighs the potential
risk(s).

**Abbreviations**

-   CT, computed tomography

-   FDG-PET, fluorodeoxyglucose positron emission tomography

-   IVU, intravenous urography

-   Med, medium

-   Min, minimal

-   MRI, magnetic resonance imaging

-   NUC, nuclear medicine

-   US, ultrasound

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are based on analysis of the current literature and
expert panel consensus.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate selection of radiologic imagine procedures for pretreatment
staging of invasive bladder cancer

#### POTENTIAL HARMS

-   The relative radiation level is high for computed tomography (CT) of
    the abdomen and pelvis with contrast, CT cystography, and CT virtual
    cystoscopy; medium for CT urography, nuclear medicine (NUC) bone
    scan of the whole body, and CT of the chest; and low for X-ray
    intravenous urography and X-ray radiographic survey of the whole
    body.

-   Positron emission tomography (PET) studies to date are not proven to
    enhance pretreatment staging and are not indicated until further
    validation and studies are completed.

-   Some patients with renal failure who have been exposed to gadolinium
    contrast agents (the percentage is unclear) have developed
    nephrogenic systemic fibrosis, a syndrome that can be fatal. Until
    further information is available, gadolinium contrast agents should
    not be administered to patients with either acute or significant
    chronic kidney disease (estimated GFR \<30 mL/min/1.73m^2^), recent
    liver or kidney transplant or hepato-renal syndrome, unless a
    risk-benefit assessment suggests that the benefit of administration
    in the particular patient clearly outweighs the potential risk(s).

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

An American College of Radiology (ACR) Committee on Appropriateness
Criteria and its expert panels have developed criteria for determining
appropriate imaging examinations for diagnosis and treatment of
specified medical condition(s). These criteria are intended to guide
radiologists, radiation oncologists, and referring physicians in making
decisions regarding radiologic imaging and treatment. Generally, the
complexity and severity of a patient\'s clinical condition should
dictate the selection of appropriate imaging procedures or treatments.
Only those exams generally used for evaluation of the patient\'s
condition are ranked. Other imaging studies necessary to evaluate other
co-existent diseases or other medical consequences of this condition are
not considered in this document. The availability of equipment or
personnel may influence the selection of appropriate imaging procedures
or treatments. Imaging techniques classified as investigational by the
U.S. Food and Drug Administration (FDA) have not been considered in
developing these criteria; however, study of new equipment and
applications should be encouraged. The ultimate decision regarding the
appropriateness of any specific radiologic examination or treatment must
be made by the referring physician and radiologist in light of all the
circumstances presented in an individual examination.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Personal Digital Assistant (PDA) Downloads

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Jafri SZ, Dinan D, Francis IR, Baumgarten DA, Bluth EI, Bush WH Jr.,
Casalino DD, Curry NS, Israel GM, Kawashima A, Papanicolaou N, Remer EM,
Sandler CM, Spring DB, Fulgham P, Expert Panel on Urologic Imaging.
Pretreatment staging of invasive bladder cancer. \[online publication\].
Reston (VA): American College of Radiology (ACR); 2007. 8 p. \[61
references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1995 (revised 2007)

#### GUIDELINE DEVELOPER(S)

American College of Radiology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

The American College of Radiology (ACR) provided the funding and the
resources for these ACR Appropriateness Criteria®.

#### GUIDELINE COMMITTEE

Committee on Appropriateness Criteria, Expert Panel on Urologic Imaging

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Panel Members*: S. Zafar H. Jafri, MD; David Dinan, MD; Isaac R.
Francis, MD; Deborah A. Baumgarten, MD; Edward I. Bluth, MD; William H.
Bush, Jr., MDE; David D. Casalino, MD; Nancy S.Curry, MD; Gary M.
Israel, MD; Akira Kawashima, MD; Nicholas Papanicolaou, MD; Erick M.
Remer, MD; Carl M. Sandler, MD; David B. Spring, MD; Pat Fulgham, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

It updates a previous published version: Jafri SZ, Shetty M, Choyke PL,
Bluth EI, Bush WH Jr, Casalino DD, Francis IR, Kawashima A, Papanicolaou
N, Rosenfield AT, Sandler CM, Segal AJ, Tempany C, Resnick MI, Expert
Panel on Urologic Imaging. Pretreatment staging of invasive bladder
cancer. \[online publication\]. Reston (VA): American College of
Radiology (ACR); 2005. 8 p. \[51 references\]

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[American College of Radiology (ACR) Web
site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonUrologicImaging/PretreatmentStagingofInvasiveBladderCancerDoc11.aspx).

ACR Appropriateness Criteria® *Anytime*, *Anywhere*™ (PDA application).
Available from the [ACR Web
site](http://www.acr.org/SecondaryMainMenuCategories/ACRStore/FeaturedCategories/QualityandSafety/ac_pda.aspx).

Print copies: Available from the American College of Radiology, 1891
Preston White Drive, Reston, VA 20191. Telephone: (703) 648-8900.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   ACR Appropriateness Criteria®. Background and development. Reston
    (VA): American College of Radiology; 2 p. Electronic copies:
    Available in Portable Document Format (PDF) from the [American
    College of Radiology (ACR) Web
    site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx).

-   ACR Appropriateness Criteria®. Relative radiation level information.
    Reston (VA): American College of Radiology; 2 p. Electronic copies:
    Available in Portable Document Format (PDF) from the [American
    College of Radiology (ACR) Web
    site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/RRLInformation.aspx).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on May 6, 2001. The information was
verified by the guideline developer as of June 29, 2001. This summary
was updated by ECRI on September 8, 2004. The updated information was
verified by the guideline developer on October 8, 2004. This NGC summary
was updated by ECRI on February 7, 2006. This summary was updated by
ECRI Institute on May 17, 2007 following the U.S. Food and Drug
Administration (FDA) advisory on Gadolinium-based contrast agents. This
summary was updated by ECRI Institute on June 20, 2007 following the
U.S. Food and Drug Administration (FDA) advisory on gadolinium-based
contrast agents. This NGC summary was updated by ECRI Institute on
December 3, 2007.

#### COPYRIGHT STATEMENT

Instructions for downloading, use, and reproduction of the American
College of Radiology (ACR) Appropriateness Criteria® may be found on the
[ACR Web
site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/ACRAppropriatenessCriteriaTermsandConditionsDoc1.aspx).

### DISCLAIMER

#### NGC DISCLAIMER

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All guidelines summarized by NGC and hosted on our site are produced
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Guidelines represented on the NGC Web site are submitted by guideline
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Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

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Date Modified: 11/3/2008