09 - Radiol Clin N Am 2007 - Imaging of Bladder Cancer.pdf - książki - Bio Med 21 - bibiariel

183

RADIOLOGIC

CLINICS

OF NORTH AMERICA

Radiol Clin N Am 45 (2007) 183–205

Imaging of Bladder Cancer

Jingbo Zhang, MD a, *, Scott Gerst, MD b , Robert A. Lefkowitz, MD a ,

Ariadne Bach, MD b

- Detection and staging

Major prognostic factors

CT imaging

MR imaging

Intravenous urography

Ultrasonography

Nuclear scintigraphy

Other diagnostic considerations

- Treatment planning

- Post-treatment imaging

- Summary

- References

Bladder cancer is the fourth most common can-

cer in men and the tenth most common cancer in

women in the United States, with 61,420 new diag-

noses and 13,060 deaths expected to occur in 2006

[1] . According to the National Cancer Institute’s

Surveillance, Epidemiology, and End Results

(SEER) Program, between 1998 and 2002, the

age-adjusted incidence and death rates for bladder

cancer were 21.3 and 4.4 per 100,000 population,

respectively. Between 1995 and 2001, the overall

5-year survival rate for bladder cancer was 81.8%

[2] . Bladder cancers occur three to four times

more often in men than in women [2,3] . The age

at diagnosis is generally older than 40 years; the me-

dian age is in the mid-60s.

The urinary bladder is an extraperitoneal struc-

ture surrounded by pelvic fat. The peritoneum

forms a serosal covering that is present only over

the bladder dome. The bladder wall consists of

four layers: uroepithelium lining the bladder lu-

men, the vascular lamina propria, the muscularis

propria consisting of bundles of smooth detrusor

muscle, and the outermost adventitia formed by

connective tissue [4] .

More than 95% of bladder tumors arise from

the uroepithelium (epithelial tumors), including

urothelial tumors (over 90%), squamous cell carci-

nomas (6% to 8%), and adenocarcinomas (2%)

[5,6] . Urothelial tumors (or transitional cell carci-

noma, TCC) exhibit a spectrum of neoplasia rang-

ing from a benign papilloma through carcinoma

in situ to invasive carcinoma [5] . Adenocarcinomas

may be of urachal origin or of nonurachal origin

[7] , with the urachal type typically occurring in

the dome of the bladder in the embryonal remnant

of the urachus [8] . Squamous cell carcinoma is as-

sociated strongly with a history of recurrent urinary

tract infection or bladder calculus [9] . Much rarer

epithelial tumors include small cell/neuroendo-

crine carcinoma (1%, with or without associated

paraneoplastic syndrome), carcinoid tumors, and

melanoma [10] . Epithelial tumors may have

a mixed histology, such as urothelial and squamous

or urothelial and adenocarcinoma. These are

treated as urothelial carcinomas [11] .

Mesenchymal bladder tumors can be benign (leio-

myoma, paraganglioma, ﬁbroma, plasmacytoma,

hemangioma, solitary ﬁbrous tumor, neuroﬁbroma,

a Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, C278D, New York, NY 10021, USA

b Cornell University, Weill Medical College, New York, NY, USA

* Corresponding author. Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, C278D, New York, NY

10021.

E-mail address: zhangj12@mskcc.org (J. Zhang).

doi:10.1016/j.rcl.2006.10.005

radiologic.theclinics.com

184

Zhang et al

and lipoma) or malignant (rhabdomyosarcoma, leio-

myosarcoma, lymphoma, and osteosarcoma) [10] .

The pathogenesis of urothelial tumors is direct

prolonged contact of the bladder urothelium with

urine containing excreted carcinogens [10] . This is

reﬂected in the propensity for urothelial carcinoma

to be multicentric with synchronous and metachro-

nous involvement of the entire urinary tract (blad-

der and upper tract) [10] . Approximately 30% of

bladder cancer patients present with multifocal dis-

ease in the bladder and sometimes widespread asso-

ciated areas of squamous metaplasia and carcinoma

in situ [12] . Out of the patients who initially present

with upper tract lesions, 11% to 13% percent will

develop additional upper tract neoplasms, while

up to 50% will develop metachronous tumors in

the urinary bladder. Only approximately 5% of pa-

tients who initially present with bladder TCC, how-

ever, will develop metachronous tumors in the

upper urinary tract, (this is especially likely to occur

when multiple bladder lesions are present) [13–

15] . Patients may start with papillary low-grade tu-

mors, which subsequently may develop into sessile,

diffuse high-grade tumors that are much more

likely to be invasive at recurrence [16] . The presence

of carcinoma in situ is associated with an increased

incidence of recurrence and an increased likelihood

of developing invasive disease [12] .

The most well-established risk factor for bladder

cancer is cigarette smoking [4] , but chemical carcin-

ogens (such as aniline, benzidine, aromatic amines,

and azo dyes) also are thought to predispose to the

development of TCC; these substances are metabo-

lized and excreted into the urine as carcinogens that

act upon the urothelium. Therefore occupation is

the second most important risk factor after smok-

ing, estimated to account for as much as 20% of

all bladder cancer in the past [17] . Increased risk

of bladder cancer still exists for workers and former

workers in the dye, rubber, and chemical industries,

and probably among painters, leather workers, and

shoemakers, as well as metal workers [18–25] . Die-

sel exhaust also has been shown to moderately in-

crease the risk of bladder cancer [26] . Analgesic

abuse and urine stasis from structural abnormali-

ties, such as horseshoe kidneys, also are associated

with an increased incidence of these tumors [13] .

A history of recurrent urinary tract infection or blad-

der calculus is related strongly to the development

of bladder cancer, squamous cell carcinoma in par-

ticular [9] . This is also evidenced by elevated risk of

bladder cancer in patients with spinal cord injury in

whom chronic cystitis is inevitable [4] . Squamous

cell carcinoma also is associated with Schistosoma

haematobium infection and accounts for 40% of ep-

ithelial tumors in endemic areas [4,27] . Adenocar-

cinoma of nonurachal origin generally is thought

to arise from metaplasia of chronically irritated

transitional epithelium. Other important risk fac-

tors associated with the patient’s medical history in-

clude prior radiation therapy to the pelvis [28] and

prior treatment for malignancy with certain chemo-

therapy agents, in particular cyclophosphamide

[4,29] . In addition, hormonal factors may play

a role in oncogenic process of bladder cancer [4] .

Although only a small fraction of patients has an

affected family member, heredity may play a role in

some cases of bladder cancer, as the risk of develop-

ing the disease increases almost twofold when

a ﬁrst-degree relative carries the diagnosis of urothe-

lial tumor [30–33] . Familial clustering of urothelial

carcinoma also has been reported [30,32] . Cytoge-

netic and molecular genetic analyses of tumors car-

ried by these families may contribute substantially

to the understanding of urothelial tumor pathogen-

esis on a molecular level [34] .

Detection and staging

It is thought that patients at high risk for bladder

cancer probably beneﬁt from screening, although

there are no conclusive data proving that screening

reduces mortality from bladder cancer [4] . Screen-

ing has been conducted mainly by hematuria test-

ing and urine cytology, although the optimal

screening test and testing interval are uncertain [4] .

The most common symptom leading to the detec-

tion of bladder cancer is hematuria, typically macro-

scopic and painless, in over 80% of patients [4,35] .

If enough urine samples are tested, nearly all pa-

tients with cystoscopically detectable bladder cancer

have at least microhematuria [36] . Among patients

presenting with macroscopic hematuria, up to

13% to 28% have bladder cancer [4] . Although

the incidence of bladder cancer is low in patients

who have microscopic hematuria, in some investi-

gations, it increases up to 7.5% in patients over 50

years of age [4,37] . The second most common pre-

sentation of bladder cancer is urinary frequency, ur-

gency, and dysuria resulting from irritation and

reduced bladder capacity [4] . Less commonly,

patients may present with urinary tract infection,

or for a more advanced lesion, urinary obstruction,

pelvic pain and pressure, or a palpable pelvic mass

[4] . Very rarely, patients present with symptoms of

advanced disease such as weight loss and abdomi-

nal or bone pain from distant metastases [4] .

When bladder cancer is suspected, numerous

diagnostic tests or procedures can be performed

to evaluate the patient, including urinalysis and

voided urine cytology, cystoscopy, and imaging

studies such as CT, MR imaging, and less frequently,

intravenous urography (IVU) [38] . Typically a pa-

tient with suspicious presentations is evaluated by

Bladder Cancer Imaging 185

ofﬁce cystoscopy to determine whether a lesion is

present. For purely papillary lesions or cases in

which only the mucosa appears abnormal, suggest-

ing carcinoma in situ, CT is not recommended, as it

rarely alters the management in these circum-

stances. Clinical staging for disease of stage T2

and above, however, is less accurate. It is estimated

that clinical staging is inaccurate in 25% to 50% of

patients who have invasive cancers [39] . Therefore

if cystoscopic appearance of the bladder tumor is

sessile, high-grade, or includes other signs sugges-

tive of invasion into muscle, CT of the abdomen

and pelvis is recommended for staging before the

patient undergoes transurethral resection of the

bladder tumor (TURBT) to conﬁrm the diagnosis

and determine the extent of tumor within the blad-

der. When muscle invasive disease in the bladder is

found by TURBT, evaluation of upper tract collect-

ing system, examination under anesthesia, and

further staging with chest radiograph and cross-

sectional imaging of the abdomen and pelvis are

recommended for complete staging. A bone scan

should be obtained when alkaline phosphatase is

elevated or a patient presents with symptoms.

Box 1: TNM staging table for bladder cancer

T—Primary tumor

TX—Primary tumor cannot be assessed.

T0—No evidence of primary tumor

Ta—Noninvasive papillary carcinoma

Tis—Carcinoma in situ

T1—Tumor invades subepithelial connective

tissue.

T2—Tumor invades muscle.

pT2a—Tumor invades superﬁcial muscle.

pT2b—Tumor invades deep muscle.

T3—Tumor invades perivesical tissue.

pT3a—Tumor invades perivesical tissue

microscopically.

pT3b—Tumor invades perivesical tissue

macroscopically.

T4—Tumor invades any of the following: pros-

tate, uterus, vagina, pelvic wall, or abdomi-

nal wall.

T4a—Tumor invades the prostate, uterus, or

vagina.

T4b—Tumor invades the pelvic wall, abdom-

inal wall (The sufﬁx ‘‘m’’ is added to the ap-

propriate T category to indicate multiple

lesions. The sufﬁx ‘‘is’’ may be added to any

T to indicate the presence of associated carci-

noma in situ.)

N—Regional lymph nodes

NX—Regional lymph nodes cannot be

assessed.

N0—No regional lymph node metastasis

N1—Metastasis in a single lymph node less

than or equal to 2 cm in greatest dimension

N2—Metastasis in a single lymph node, greater

than 2 cm but less than or equal to 5 cm in

greatest dimension; or multiple lymph no-

des, less than or equal to 5 cm in greatest

dimension

N3—Metastasis in a lymph node, greater than

5 cm in greatest dimension

M—Distant metastasis

MX—Distant metastasis cannot be assessed.

M0—No distant metastasis

M1—Distant metastasis

Major prognostic factors

Bladder cancer is a heterogeneous and frequently

multifocal disease with a variable clinical course.

The major prognostic factors in carcinoma of the

bladder are the depth of invasion into the bladder

wall and the degree of differentiation or pathologic

grade of the tumor. Approximately 70% to 80% of

patients with newly diagnosed bladder cancer will

present with superﬁcial bladder tumors (ie, stage

Ta, Tis, or T1) that are mostly well differentiated

and often can be cured. The pathologic grade of tu-

mor has a greater impact on the management of

these noninvasive tumors, because most muscle-

invasive tumors (T2 and above) are high grade.

The most commonly used staging system is that

of the American Joint Committee on Cancer

(AJCC), the TNM system [40] ( Box 1 ). The patient’s

overall disease stage is determined by AJCC stage

groupings ( Box 2 ). Cancer-speciﬁc survival for pa-

tients who have bladder cancer is correlated highly

with the tumor stage ( Table 1 ). The 5-year survival

rate is 55% to 80% for patients with bladder cancer

conﬁned to the lamina propria treated with cystec-

tomy, but it drops to 40% with muscular invasion,

20% with perivesical invasion, and 6% with meta-

static disease [41] .

Precise staging is critical for preoperative plan-

ning and prognosis. The clinical staging of bladder

cancer is determined by the depth of invasion of the

bladder wall, performed with a cystoscopic exami-

nation that includes a biopsy, and examination un-

der anesthesia to assess the size and mobility of

palpable masses, the degree of thickening of the

bladder wall, and the presence of extravesical exten-

sion or invasion of adjacent organs. Clinical staging

often underestimates the extent of tumor, particu-

larly in cancers that are less differentiated and

more deeply invasive.

CT imaging

CT is the imaging modality of choice for the work-

up of patients presenting with hematuria. It also is

indicated in patients with high-grade bladder can-

cer raising suspicion for muscle invasion. Routine

contrast-enhanced CT examinations are useful for

186

Zhang et al

Box 2: Stage grouping for bladder cancer

Stage 0a—Ta, N0, M0

Stage 0is—Tis, N0, M0

Stage I—T1, N0, M0

Stage II

T2a, N0, M0

T2b, N0, M0

Stage III

T3a, N0, M0

T3b, N0, M0

T4a, N0, M0

Stage IV

T4b, N0, M0

Any T, N1, M0

Any T, N2, M0

Any T, N3, M0

Any T, any N, M1

iodinated intravenous contrast. The advantages of

CTU are made possible by multidetector helical

CT with volumetric acquisition, which provides

fast acquisition of high-resolution images and al-

lows multiplanar reconstruction.

Although some institutions use combined axial

CTU with conventional overhead radiograph or

CT scanned projection radiograph (tomogram/

topogram) imaging [44] , dedicated CTU with im-

age postprocessing has proven to be robust and ver-

satile, supplanting combined imaging at many

institutions. Protocols differ among institutions.

At the authors’ institution, CTU is performed with-

out oral contrast, using combined intravenous non-

ionic iodinated contrast (150 mL at 2.5 mL/s in

a patient with normal renal function) and saline

bolusing (400 cc). Thin-section precontrast, post-

contrast, and delayed excretory phase images are

obtained. Precontrast images covering the area

from the top of the kidneys to the bottom of the

bladder are essential for evaluating the presence of

urinary calculi. They also provide a baseline attenu-

ation measurement for evaluating the degree and

pattern of enhancement for any incidentally identi-

ﬁed lesions of the urinary tract [45] . Postcontrast

images typically are performed during the renal pa-

renchymal phase (approximately 90 seconds after

initiation of the intravenous contrast injection),

and they cover the entire abdomen and pelvis.

These images are helpful in the identiﬁcation of en-

hancing urothelial lesions, incidental renal cortical

masses, and other abdominal/pelvic abnormalities

such as hepatic metastases and lymphadenopathy

Earlier phase imaging, such as arterial phase imag-

ing targeting the kidneys or bladder, has been sug-

gested by some investigators to be useful for

evaluating TCC [46] . The excretory phase images

(typically achieved with a scan delay of 10 minutes

or more) provide substantial additional informa-

tion, both in conﬁrming enhancing lesions as true

lesions and not pseudolesions related to focal opa-

ciﬁed urine arising from a ureteral jet within the

bladder lumen [47] , and in demonstrating discrete

ﬁlling defects caused by tumor not evident on ear-

lier scans. If the urinary tract is not well distended

and opaciﬁed with contrast throughout its entire

course, then additional delayed images may be ac-

quired targeting the nonopaciﬁed portion up to

two times. Putting the patient in the prone position,

applying abdominal compression, or both, may

help distend the urinary collecting system. In the

setting of frank hydronephrosis, the patient may

be allowed to return to the CT department 30 or

60 minutes later for delayed imaging. The excretory

phase images are reconstructed further into thin

overlapping sections, which then are transferred

to a workstation for three-dimensional post-

detecting metastases, but they may be inadequate

for detecting and staging local urothelial lesions.

In the setting of hematuria, CT urography (CTU)

can be used as a one-stop-shop examination to eval-

uate the entire urinary system and diagnose possi-

ble causes of hematuria, including lithiasis, other

benign etiologies, renal parenchymal lesions, and

urothelial neoplasms, thus eliminating the need

for additional imaging. In the presence of urothelial

tumor, the detailed evaluation of the entire urinary

system provided by CTU [42] is essential, as pa-

tients with urothelial tumor may have multifocal

disease. In terms of cancer staging, CTU can detect

direct perirenal, periureteral, and extravesical tumor

spread, as well as lymphadenopathy and distant

metastases. Compared with traditional excretory ur-

ography, CTU requires a shorter examination time

and has greater accuracy for detecting urothelial le-

sions [43] . CTU also allows more detailed evalua-

tion of the renal parenchyma and perirenal tissues

and permits better evaluation of obstructed collect-

ing systems than does excretory urography [13] .

Therefore, for evaluating urinary tract neoplasms

and the work-up for hematuria, CTU is the imaging

modality of choice for patients who can tolerate

Table 1: Survival rates for bladder cancer

by stage

Bladder cancer

stage

Relative 5-year survival

(1998–2003)

95%

85%

55%

III

38%

16%

Data from the National Cancer Database. Comission on

cancer, American College of Surgeons, Chicago, IL.

Bladder Cancer Imaging 187

Fig. 1. A coronal maximum intensity projection image

obtained from excretory phase CT urography (CTU)

shows bilateral urinary collecting systems and blad-

der are opaciﬁed with contrast.

on the postprocessed images, however, needs to be

conﬁrmed on the axial source images. In addition,

three-dimensional reconstructions alone have

been shown to have a suboptimal sensitivity in de-

tecting upper tract lesions, even in retrospect [48] .

Therefore they are considered supplementary only

and do not replace acquired axial source images

for accurate interpretation. In one study by Caoili

and colleagues, 24 of 27 upper urinary tract neo-

plasms were detected with CTU. Of note, 21 of 27

lesions in this study were missed using the three-

dimensional reconstructed images alone (especially

small tumors or tumors that presented with wall

thickening without distortion of the lumen; similar

types of tumors frequently are missed on excretory

urography). Twenty of the 24 detected lesions

were visible on the axial source images using

a soft tissue window that allowed visualization of

ureteral or pelvic wall thickening. The remaining

four lesions only could be seen using a wide win-

dow (bone window) that allowed visualization of

small intraluminal lesions that were obscured on

soft tissue windows by the high density of the ex-

creted contrast material [43] . Therefore it was sug-

gested that the axial source images should be

viewed with both bone and soft tissue windows to

achieve the highest diagnostic accuracy [43] .

Virtual cystoscopy, obtained by manipulating

CTU data acquired through the contrast-ﬁlled blad-

der during the excretory phase, allows navigation

within a three-dimensional model, and has shown

promise for detecting bladder mucosal lesions [49] .

Further investigation to assess for added value of

virtual cystoscopy, when compared with current

processing ( Fig. 1 ). Table 2 shows a typical CTU

protocol at the authors’ institution for a 16-slice

multidetector scanner (LightSpeed 16; General

Electric, Milwaukee, Wisconsin).

Numerous different image postprocessing algo-

rithms (either volume rendering of entire data set,

thick slab averaging, or maximum intensity projec-

tions), are available for CTU to provide three-di-

mensional visualization of the urinary tract, or

reconstruct IVP-like projectional images. The major

role of postprocessed images is to provide a general

overview of the anatomy and accentuate the areas

of abnormality ( Fig. 2 ). Any abnormality visualized

Table 2: CT urography

Precontrast

Parenchymal

Excretion

Pitch

0.9375

1.375

Scan rotation speed

18.75 mm/rotation

13.75 mm/rotation

Slice thickness/

spacing (mm)

2.5 2.5 mm

Tube rotation speed

0.8 s rotation

Anatomical coverage

Top of kidneys to

pubic symphysis

Top of liver to pubic

symphysis

Top of kidneys to

pubic symphysis

Reconstructions

N/A

1.25 0.8 mm

Injection (rate/time/

volume)

N/A

1. 200 cc intravenous

saline bolus

N/A

2. 150 cc at 2.5 cc/s

3. 200 cc intravenous

saline bolus

Injection to scan

delay (sec)

N/A

92 s after beginning

of intravenous

contrast injection

10 minutes

Oral contrast

None

Abdominal compression

Apply unless patient has known hydronephrosis/obstruction, recent surgery, or abdominal pain. Apply just before begin-

ning injection and release at 5 minutes.

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