Bladder Cancer

Suzanne Bonington and Jeremy A.L.Lawrance

BACKGROUND INFORMATION Epidemiology

Bladder cancer is the most common malignancy of the urinary tract, and represents 4.5% of all new malignancies. The peak incidence is in the 6th and 7th decades, although there is an increasing number of patients who present under the age of 30. The male to female ratio is 4:1. The age standardised incidence rates/100000 population for males is 19.5 in the UK and 23 in the USA. For females it is 6/100000 population both in the UK and USA.

There is an increased risk of bladder cancer with exposure to various aromatic amines, causing an occupational hazard in the chemical, rubber and paint industries. There is also an association with diesel fumes, long term phenacetin use, and smoking. Squamous cell carcinoma is associated with chronic urinary tract infections and prolonged schistosomiasis infection.

Histopathology

Bladder tumours are predominantly epithelial in origin and 90-95% of these are transitional cell type with approximately 50% arising from the lateral bladder walls and 20% from the region of the trigone. Squamous cell, or mixed transitional cell and squamous cell carcinoma, accounts for 5-10% of malignancies. Adenocarcinomas, which account for 2-3% of malignancies, are more prevalent in patients with a patent urachus and thus usually occur in the urachal remnant. Other cell types such as small cell are extremely rare, accounting for less than 1% of cases. At presentation about one third of tumours are multifocal in origin. Approximately two thirds of bladder tumours are superficial and are usually papillary. One third show infiltration into or beyond the bladder wall.

Patterns of tumour spread

Direct spread of tumour occurs into the perivesical fat, pelvic organs and to the pelvic sidewalls. Lymph node metastases are rare in superficial tumours, but occur in 30% of patients when the deep muscle layer of the bladder is involved and in 60% of cases where there is extravesical tumour spread. The first lymph nodes involved are the anterior and lateral paravesical nodes and the pre-sacral nodes. Subsequent nodal spread is to the internal iliac, obturator and external iliac nodes and finally the common iliac and para-aortic nodes. Common iliac and paraaortic nodes are considered as distant metastases (MI) in the TNM staging system. Occasionally, metastatic lymph nodes may be identified above the diaphragm. Distant metastases to the bones, lungs, brain and liver are late features of bladder cancer.

Two main classifications for bladder cancer exist—the TNM system and the Jewett-Strong-Marshall (JSM) system. The TNM system is now the system in general use as it provides greater detail about superficial lesions and also defines extravesical spread more clearly. A summary of the TNM system is seen in Table 11.1, and illustrated in Diagram I.

Table 11. 1. TNM (2002) staging of bladder cancer

TNM JSM Histopathological findings

Tis Carcinoma in situ

Ta 0 Papillary tumour confined to the epithelium (mucosa)

T1 A Tumour invades subepithelial connective tissue (lamina propria)

T2 Tumour invades muscle

T2a B1 Tumour invades superficial muscle (inner half)

T2b B2 Tumour invades deep muscle (outer half)

T3 C Tumour invades perivesical tissue

T3a Tumour invades perivesical fat microscopically

T3b Tumour invades perivesical fat macroscopically

T4a D1 Tumour invades surrounding organs—prostate, uterus or vagina

T4b Tumour invades pelvic or abdominal wall

N0 No regional lymph node metastases

N1 D1 Metastasis in a single lymph node 2.0 cm in greatest dimension

N2 D1 Metastasis in a single lymph node >2.0 cm but =S5.0 cm in greatest dimension, or multiple nodes

N3 D1 Metastasis in a lymph node >5.0 cm In greatest dimension M0 No distant metastasis

Ml D2 Distant metastasis

Prognostic indicators

• Tumour stage. Five-year survival decreases from approximately 70% for T1 disease to 5-10% for T4 disease. A major adverse feature is the presence of any lymph node metastases.

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Diagram 1: T Staging of Bladder Cancer

• Tumour grade. High histological grade tumours are more likely to become infiltrative and to metastasise, irrespective of tumour stage at presentation.

• Multiple lesions. Multifocal tumour adversely affects survival.

• Other factors. The following have been identified as adverse features: hydronephrosis, anaemia, tumour size, expression of blood group substances, expression of epidermal growth factor receptors, mutation of p53, up-regulation of Rb and other oncogene expression.

Treatment

Patients with superficial bladder tumours are treated with regular local endoscopic resection and intravesical chemotherapy or immunomodulators. Patients with frequent recurrences or high-grade disease are often treated with a radical cystectomy. Stage 2a-3a disease, with muscle invasion but minimal perivesical spread, is most commonly treated by radical cystectomy and lymph node resection, or with radiotherapy after chemotherapy. Such patients can be treated with radical radiotherapy, although this is decreasing in popularity. Advanced disease is palliated with either mitomycin-based chemotherapy or radiotherapy.

MR IMAGING OF BLADDER CANCER Technique

The bladder should be moderately full to separate the walls, but not too distended as to cause degradation of the images by motion artifact due to patient restlessness. This can usually be achieved by asking the patient to micturate 2 hours before the examination. Respiratory motion is limited by putting a band across the patient's abdomen. In practice this is achieved with the phased-array pelvic coil. Many centres use either hyoscine butylbromide or glucagon to reduce artifact from bowel motion. A standard technique using T1 and high resolution turbo fast spin echo T2 sequences is used for staging. The use of orthogonal planes frequently gives valuable additional information. Sagittal and coronal planes are particularly useful for assessing tumours at the dome and trigone of the bladder.

Fat saturated/STIR sequences with intravenous contrast are sometimes used and studies suggest a 9-14% improvement in staging accuracy with contrast-enhanced imaging. Enhancement should appear earlier and be greater in the tumour compared to the normal bladder wall. Fast dynamic MR imaging, using one image every 2 seconds, can be useful in differentiating tumour which enhances earlier at approximately 6 seconds, from post biopsy change which enhances after approximately 10 seconds, or from radiation effects.

Other modifications in technique include the use of endorectal coils. These provide excellent detail of the dorsal bladder wall, but have the drawback that the entire bladder and rest of the pelvis cannot be assessed.

If intravenous contrast has been given during the examination a breath-hold Tl-weighted MR angiographic sequence can produce a contrast urogram which may be helpful to view the upper renal tracts, where synchronous tumours may be seen in 0.5% of patients.

Current indications

Cystoscopic examination and biopsy remain the basis for evaluation of superficial tumours. With invasive disease, clinical evaluation with bimanual palpation and assessment of adherence to local structures is only 50-75% accurate, so that MR imaging may be helpful in this circumstance.

Staging accuracy

MRI has been shown to be superior to clinical staging for patients treated with radiotherapy in that MR stage correlated better with risk of treatment failure and cancer-specific survival.

The accuracy of MR in staging of bladder cancer varies between 73 and 96%. This is 10-30% higher than achieved with CT. The improvement in accuracy is due to better visualisation of the dome and trigone of the bladder and superior assessment of adjacent organ invasion. MR staging accuracy is less for low stage tumours due to the difficulty in differentiating between superficial and deep muscle invasion, and early extra- vesical spread. In this tumour group, it remains superior to CT due to the ability of MR to identify the layers of the bladder wall.

Imaging features

Primary tumour

On T1W sequences, the perivesical fat appears high signal, the normal bladder wall intermediate signal and urine in the bladder low signal. In general, the individual muscle layers of the bladder wall are not dis-

criminated. This sequence is most useful for assessing extra-vesical spread of tumour into the perivesical fat as either a mass or an intermediate signal stranding of the fat. T1W sequences are also useful for assessing the skeleton for bone metastases.

On T2W images the bladder muscle layer is of low signal intensity and tumour is of intermediate signal intensity,slightly higher than that of the bladder wall. This sequence is therefore used to assess bladder wall invasion and is useful for evaluating tumour extension into the prostate, uterus or vagina, since intra-organ anatomy is best delineated on this sequence.

Nodal disease

Features suggestive of nodal; involvement include nodal size, round shape and the presence of asymmetrical clusters of nodes. Nodes are considered enlarged if they measure more than 8.0 mm in short axis if round, and 10.0 mm if oval shaped. Note that in bladder cancer the long axis measurement of a nodal mass is the N stage determinant.

Post treatment and recurrence

After cystectomy, the bladder bed may demonstrate low signal intensity fibrosis and bowel often prolapses into it or becomes adherent to the fibrotic tissue. The ileal loop diversion may be visualise, usually in the right iliac fossa. Neobladder formation is performed only occasionally in patients with small tumours localised to the bladder dome. Local tumour recurrence post cystectomy is usually evident as a solid mass of intermediate to high signal in the bladder bed.

Radiation therapy usually results in low signal fibrous change, but it can also cause generalised or focal bladder wall thickening of intermediate to high signal intensity on T2 images for up to 4 years after treatment making differentiation from tumour difficult. Dynamic contrast enhanced scans have been shown to be useful in differentiating recurrent tumour from post treatment effects.

Pitfalls of MRI

• Differentiation between T1, T2a, T2b and T3a tumours. It can be difficult on MRI to differentiate between the superficial and deep muscle layers of the bladder wall and to identify small volume extra-vesical extension. Whilst this differentiation affects prognosis, it does not affect management and is usually determined histologically.

• Over- or under-distension of the bladder. If the bladder is too full, images may be degraded by motion artifact. If the bladder is poorly distended, the tumour and bladder wall may not be well visualised. Motion artifact can also degrade images at the dome of the bladder. Care in patient preparation and administration of smooth muscle relaxants may prevent these problems.

• Recent cystoscopic biopsy causing post-operative oedema and inflammatory reaction can result in over-staging. It is therefore imperative to have accurate information regarding the dates and depths of biopsies. In some circumstances, it may be necessary to rescan the patient at a later date.

• Chemical shift artifact can potentially impair staging by affecting the perception of tumour depth of invasion. This is overcome using orthogonal planes and adjusting machine parameters.

• Differentiation between late fibrosis, granulation tissue and residual/recurrent tumour may be difficult. Tumour is more likely if there is a new or enlarging mass, or new disease outside the treated area. Dynamic contrast-enhanced sequences may be helpful when tumour should enhance earlier than fibrosis.

FURTHER READING

1. Husband JES. (1998) Bladder cancer. In: Imaging in Oncology. (eds Husband JES and Reznek R). Isis Medical Media Ltd, Oxford, UK pp. 215-238. Good overview of bladder cancer.

2. Urinary Bladder. (2002) In: AJCC Cancer Staging Manual. 6th edition. (eds Greene FL, Page DL, Fleming ID et al.). Springer-Verlay, NewYork, USA pp. 335-340. Current TNM staging of Bladder cancer. Succinct summary ofprognostic indicators.

3. Barentsz JO, Jager GJ and Witjes JA. (2000) MR imaging of the urinary bladder. Oncologic MR imaging. Magn. Reson. Imaging Clin. N. Am. 8(4): 853-867. Good description of technique.

4. MacVicar AD. (2000) Bladder Cancer staging. BJU 86 Suppl I: 111-122. Compares the use of MR and CT in staging bladder cancer.

5. Hall RR and Prout GR. (1990) Staging of bladder cancer: is the tumour, node, metastasis system adequate? Semin. Oncol. 17(5): 517-523. Discusses the problems with the TNM staging system for the bladder and underlines the key areas which significantly alter clinical management

6. Robinson P, Collins CD, Ryder WD et al. (2000) Relationship of MRI and clinical staging to outcome in invasive bladder carcinoma treated with radiotherapy. Clin. Radiol. 55(4): 301-306. Identifies the most important findings on MR that alter prognosis.

Bladder Distension
Figure 11.1. Normal bladder—moderate distension.

(a) and (b) Transaxial T2W1 of the bladder. The normal bladder muscle layer demonstrates low signal intensity (arrow), the mucosa intermediate signal (crossed arrow) with high signal urine within the bladder (B) and intermediate signal perivesical fat (F). In (a), the normal high signal return from the seminal vesicles (S) is seen. In (b), a more cranial section, the distal ureters (U) are seen as they enter the bladder (B). The vas deferens (VD) is also clearly seen.

Figure 11.2. Normal bladder—extreme distension.

(a) Midline sagittal T2W1, (b) transaxial T2W1 and (c) coronal T2W1 through the bladder, following an injection of 20 mg hyoscine butylbromide.The normal bladder muscle is seen as a thin band of low signal intensity (arrows), the mucosa is a fine line of intermediate signal on the inner aspect of the muscle layer (crossed arrows) with high signal urine within the bladder. Urethral meatus (open arrow), bladder trigone (arrowheads).

Detrusor Hypertrophy
Figure 11.3. Bladder wall trabeculation.

Transaxial T2W1 and (b) sagittal T2W1 through the bladder. These images demonstrate circumferential low signal thickening of the bladder wall (arrows) in keeping with detrusor muscle hypertrophy due to chronic bladder outlet obstruction

Detrusor Muscle Hypertrophy
Figure 11.4. T2a Bladder cancer

(a) Sagittal T2W1 and (b) fat saturation contrast-enhanced T1W1 demonstrating an enhancing tumour invading the superficial bladder muscle (arrows). The intact outer bladder wall is demonstrated (open arrow). The patient has benign prostatic hypertrophy (asterisk). (Courtesy of Dr. M.Haider, Princess Margaret Hospital, Toronto.)

Detrusor Hypertrophy
Figure 11.5. Multifocal bladder cancer, with areas showing T2a, T2b and T3b tumour.

Sagittal T2W1 through the bladder. There are multiple nodules of intermediate signal tumour involving the superficial bladder muscle (arrows). These areas show an intact outer low signal bladder wall (crossed arrows). Lying adjacent to this is abnormal intermediate signal that has extended across the full thickness of the bladder wall (arrowheads) indicating T2b tumour. One of the focal areas of tumour shows a deficit of the low signal bladder wall with intermediate signal extending across the whole thickness of the bladder wall, with subtle extension into the perivesical tissues (open arrow), this area is therefore radiologically a T3b tumour.

Mri Perivesical Fat Infiltrations

Figure 11.6. T3b Bladder cancer.

(a) Transaxial T1W1 and (b) transaxial T2W1 of a male patient with transitional cell carcinoma (T) of the bladder demonstrating transmural extension with stranding within the perivesical fat (arrows). There are also multiple serpiginous structures (open arrows) in the perivesical fat immediately adjacent to the tumour, which are of intermediate signal on T1 and high signal on T2. These are perivesical vessels and could be confused with extra-vesical tumour if only the T1W sequence was assessed. The filling defect within the bladder represents benign prostatic hypertrophy (arrowheads).

Figure 11.7. T3b Bladder cancer.

Transaxial T2W1 demonstrating extension of tumour into the perivesical fat. Note the normal bladder wall demonstrates low signal intensity (open arrows) while the tumour demonstrates intermediate-to-high signal intensity (T), outlined by high signal urine and intermediate to high signal intensity perivesical fat. The tumour is involving the right ureteric orifice and causing a right-sided hydroureter (U). Right external iliac lymph node (N). Uterus (arrowhead). Rectum (R).

Figure 11.8. T4a Bladder cancer.

Sagittal T2W1. There is a large bladder tumour arising from the base of the bladder and extending along the postero-superior bladder wall. The tumour is extending through the posterior bladder wall and perivesical fat and is invading the vagina (arrows) and lower cervix (crossed arrow). Uterus (asterisk), rectum (R), symphysis pubis (S).

Fat Vagina

Figure 11.9. T4a Bladder cancer.

Sagittal T2W1 lobulated tumour (T) is invading the prostate and inferior aspect of the seminal vesicle (asterisk).

Figure 11.10. T4b Bladder cancer.

Transaxial T2W1 of the bladder. There is a large bladder tumour (T) extending to the rectus sheath anteriorly

(arrows). There is also tumour arising in the posterior bladder (asterisks) which is not invading muscle (T2 or less) but is obstructing the left ureter(U).

Baldder Cancer T4b
Figure 11.11. T4b Bladder cancer.

(a) and (b) transaxial T2W1 and (c) coronal T2W1 demonstrating a large bladder tumour (T) extending to the rectus sheath anteriorly (arrows) and to the left pubic bone inferiorly (open arrows).The cortex appears slightly irregular and thinner than the adjacent and contra-lateral pubic arch, with a long area of contact between tumour and bone. An inguinal node (N) is noted, which has the same signal intensity as the primary tumour and is therefore likely to be metastatic.This is an unusual site for nodal disease from a bladder tumour but is likely to be secondary to the tumour extension into the pubic bone.

Figure 11.12. T3b N1 Bladder cancer.

Transaxial T2W1 of the bladder. There is a large intermediate signal tumour (T) involving the right anterolateral bladder wall, extending into the perivesical fat. Multiple small perivesical nodes are seen (arrowheads). These are noted to be of a similar signal intensity to the main bladder tumour. A right internal iliac node (N) is seen with similar signal intensity to the tumour proper making it more likely to be metastatic.

Metastatic Obturator

Figure 11.13. N1 Bladder cancer.

Transaxial T2W1 demonstrating a single intermediate signal left obturator node^2.0 cm in long axis diameter (N) and an intermediate to low signal bladder tumour (T). Left external iliac vessels (V).

Figure 11.14. N2 Bladder cancer.

Transaxial T2W1 showing bilateral metastatic obturator nodes (N). The right obturator node measures between 2.0 and 5.0 cm in greatest dimension, and has an irregular margin anteriorly (arrowheads) indicating extra-capsular extension.

Extra Capsular Extension
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