Bladder Cancer Staging

Local tumor extension, the degree of lymph node and distant metastases, and histologic tumor type largely determine treatment and prognosis. Therefore, exact staging is imperative. To determine local tumor extension (T), presence of lymph node (N) and distant metastases (M), the International Union against Cancer proposed a uniform clinical staging method (Table 1). In this table, a correlation is also presented between the TNM-system and MRI-findings. Patients with superficial tumors, i.e., tumors without muscle invasion (stages Ta and T1) are treated with local endoscopic resection followed by adjuvant intravesical installations. Patients with a tumor invading the muscle layer of the bladder wall or with minimal perivesical extension (stages T2a to T3a) will be treated by radical cystectomy and lymphadenectomy. However, if the tumor is in a more advanced stage (stages T3b-T4b) or if there are nodal or distant metastases, the patient will have palliative chemo- or radiation therapy.

Local Staging

Bladder tumors demonstrate different patterns of growth: papillary, sessile, infiltrative or mixed. Papillary tumors are usually superficial (stage T1 or less. i.e., with no muscle wall infiltration) and are best demonstrated on T1-weighted images in which the intermediate signal intensity of the intraluminal tumor is outlined by surrounding low signal intensity urine. On T2-weighted images, the signal intensity of both bladder tumor and intravesical urine increase, and intraluminal projections of bladder tumors may be less conspicuous than on T1-weighted images [66-69]. Papillary transitional cell carcinoma of the bladder has a loose connective tissue stalk. On MRI, the stalk is defined as a structure that extends from the bladder wall to the center of the tumor, with signal intensity different from that of the tumor [84]. Most of stalks show lower signal intensity than tumor on T2-weighted images, less enhancement on dynamic images and stronger enhancement on delayed enhanced images (Fig. 17). The

Fig. 17. Papillary stage T1 tumor with stalk (arrowhead). a On the T2-weighted tSE image, low signal intensity muscle is not disrupted by higher signal intensity tumor. In the center of the papillary tumor a low signal intensity stalk (arrowhead) can be seen. b Post-Gd fat saturated T1-weighted image shows that the stalk has more enhancement than the rest of the tumor (arrowhead)

Fig. 17. Papillary stage T1 tumor with stalk (arrowhead). a On the T2-weighted tSE image, low signal intensity muscle is not disrupted by higher signal intensity tumor. In the center of the papillary tumor a low signal intensity stalk (arrowhead) can be seen. b Post-Gd fat saturated T1-weighted image shows that the stalk has more enhancement than the rest of the tumor (arrowhead)

identification of the stalk of a polypoid tumor may be an important observation to exclude muscle wall invasion of the tumor [84].

Muscle wall infiltrative tumors (stages T2a or above) present as a diffuse or focal thickening of the bladder wall with increased signal intensity on T2-weighted images. This increase is in contrast to the low signal intensity of normal bladder wall. Early contrast enhanced images may help to recognize muscle wall infiltration. Findings suggesting superficial tumors are: smooth muscle layer, tenting of the bladder wall, fern-like vasculature and uninterrupted submucosal enhancement. Findings that suggest muscle invasion are: irregular wall at the base of the tumor, focal wall enhancement or wall thickening around the tumor.

MRI can differentiate between neoplastic infiltration of bladder wall and bladder wall hypertrophy secondary to outlet obstruction. In bladder wall hypertrophy, the wall is diffusely thickened (more than 5 mm), but no alternation of the low signal intensity wall is present on T2-weighted images.

Muscle wall invasion is separated into superficial (stage T2a) and deep (stage T2b). In stages T2b, the low signal intensity layer of the bladder wall is disrupted on T2-weighted images by the higher signal tumor (Fig. 11b). Stage T2b cannot be separated on MRI from stage T3a (microscopic fat infiltration). Macroscopic tumor extension through the bladder wall into the perivesical fat (stage T3b) will cause a focal irregular decrease of signal intensity of the fat on standard T1- or T2-weighted images (Fig. 18a). Contrast-enhanced images with fat saturation also show tumor (enhancement) in the perivesical fat. Invasion of adjacent organs may be inferred from the extension of abnormal tumor signal intensity through fat planes into adjacent structures (Fig. 18b). This is well demonstrated with contrast-enhanced images. Invasion of the seminal vesicles can be demonstrated by an increase in vesicular size, decrease in signal intensity on T2-weighted images and obliteration of angle between the seminal vesicle and the posterior bladder wall (Fig. 19). Invasion of the prostate and rectum is seen as direct tumor extension with an increase of signal intensity. Obliteration of the angle between bladder and prostate also indicates prostate invasion. Invasion of the pelvic side-

Fig. 18. Stage T3b urinary bladder cancer infiltrating perivesical fat (arrows). Both on (a) T2-weighted tSE and (b) post-Gd fat-saturated Tl-weighted image, bladder cancer at right latero-dorsal wall can be seen with macroscopic infiltration of perivesical fat (arrows)

Fig. 19. Stage T4a urinary bladder cancer infiltrating right seminal vesicle (arrows). T2-weighted tSE image shows hypointense intravesical mass arising from right lateral wall with obliteration of fat plain between the bladder and right seminal vesicle and abnormal signal intensity of left seminal vesicle denoting invasion by the tumor (arrows)

Fig. 19. Stage T4a urinary bladder cancer infiltrating right seminal vesicle (arrows). T2-weighted tSE image shows hypointense intravesical mass arising from right lateral wall with obliteration of fat plain between the bladder and right seminal vesicle and abnormal signal intensity of left seminal vesicle denoting invasion by the tumor (arrows)

wall (stage T4b) is seen on T1-weighted images as a loss of normal fat plane between bladder wall (tumor) and the vessels or musculature of the sidewall, or on T2-weighted images as invasion of the sidewall musculature in by intermediate to high signal intensity tumor (Fig. 20).

As clinical staging is not reliable to determine tumor extension beyond the bladder wall, other methods are needed. CT is a valuable addition, but since the introduction of pelvic MR imaging in 1983, several reports have shown the superiority of this technique for staging urinary bladder carcinoma [57].

Bladder Carcinoma Mri
Fig. 20. Stage T4b urinary bladder cancer (T) infiltrating the ventral abdominal wall. T2-weighted tSE image shows large intravesical mass arising from anterior bladder wall with abnormal high signal intensity in muscles of anterior pelvic wall denoting invasion by the tumor (arrows)

MR imaging appears to be superior to CT scanning for staging carcinoma of the urinary bladder. Multi-planar imaging allows better visualization of the bladder dome, trigone, and adjacent structures such as the prostate and seminal vesicles. The accuracy of MR imaging in staging bladder cancer varies from 73% to 96%. These values are 10-33% higher than those obtained with CT [61]. Recently, several reports have been published on the staging of urinary bladder carcinoma with the use of IV-Gd contrast. A 9-14% increase in local staging accuracy has been reported using these contrast agents. Furthermore, when using contrast agent, visualization of small tumors (> 7 mm) improves. The most accurate staging results using IV gadolinium contrast material are obtained with very fast T1-weighted sequences [56]. This can be explained by earlier enhancement of tumors compared to surrounding tissues. Although contrast-enhanced MR imaging has advantages over the use of unenhanced T2-weighted sequences, such as higher SNR ratio and shorter acquisition time, it is advised not to skip the T2-weighted images. Large prospective studies in this regard are necessary.

Lymph Node Staging

Normal nodes can be recognized with MRI down to a size of 2 mm. With multiplanar imaging, both the size and shape of the nodes can be assessed. The maximal length (long axis) and the minimal axial size of the node can be determined. Round nodes can be distinguished from oval nodes by using an index that divides the axial size by the long axis. Lymph nodes are considered rounded when this index is in-between 1.0 and 0.8, and spheric or elongated if this index is greater than 0.8. The cut-off value for the minimal axial diameter is 10 mm for a spherical/elongated node and 8 mm for a rounded node. An asymmetric cluster of small lymph nodes is also considered to be pathologic [58].

Lymph node metastasis in patients with superficial tumors (less than stage T2) is rare, but if the deep muscle layer is involved (stages T2a and higher) or if extravesi-cal invasion is seen, the incidence of lymph node metastasis rises to 20-30% and 50-60%, respectively. A non-invasive, reliable method for detecting and staging nodal metastasis would reduce the extent of surgery. Currently, there are five imaging techniques described for nodal staging: lymphangiography, CT, MRI, and 18FDG positron emission tomography (PET) scanning.

Bipedal lymphangiography is no longer used as an imaging method, although it has the capacity to show mi-crometastases in normal-sized nodes. Its inability to depict internal iliac nodes and its invasiveness are major drawbacks.

CT and MRI

Detection of lymph node metastases has very important clinical consequences. If metastatic disease is present, usually curative cystectomy will no longer be performed. Current imaging techniques can only show nodal size. Different sensitivities and specificities are acquired depending on the selection of cut-off size for lymph nodes [85]. Recently Jager and co-workers [58] showed that using a three-dimensional (3D) high-resolution technique, not only nodal size, but also nodal shape could be assessed. Using the nodal shape in relation to the cut-off size also improved their results. They obtained an accuracy of 90% and a positive predictive value of 94% [60]. This is clinically relevant as a high positive predictive value in the detection of nodal metastasis can facilitate the indication for (MR-guided) biopsy [86]. In case of a positive biopsy, this can avoid an invasive pelvic lymph node dissection. Cross-sectional imaging modalities like CT and (3D) MR imaging have a low sensitivity (76%) as metastases in normal sized lymph nodes are still missed, since both modalities use the non-specific criterion of size to distinguish between normal and malignant nodes [4, 31]. Although fast dynamic MRI has been shown to improve sensitivity by showing fast and high enhancement in metastatic nodes, specificity decreases. In addition, fast dynamic is further limited by its low resolution and pronounced vascular artifacts [56].

Staging PLND still remains the most sensitive method for assessing lymph node metastases and thus continues to be the first step in the management protocol. Cost-effective analysis performed by Wolf et al. [86] pointed out that imaging should be restricted to patients with a high probability of lymph node metastases. Thus they concluded that imaging was superior to no imaging only when the pretest probability of lymph node metastasis was high, i.e., if tumor infiltration is in or beyond the muscular layer of the bladder wall.

The most important parameter was the sensitivity of cross-sectional imaging for lymph adenopathy. Pelvic imaging combined with fine needle aspiration has also been investigated. The data of Wolf et al. [86] suggest that only a subset of patients at high risk for lymph node metastasis benefits from cross-sectional imaging and pre-operative lymph node sampling.

Bone Marrow Metastases

Currently, the mainstay for the detection of bone metastases is a radionuclide bone scan. However, MR imaging is superior to 99mTc bone scan in assessment of bone marrow involvement. The high sensitivity of MRI for evaluating bone marrow metastasis makes it an ideal tool for detecting suspected osseous metastatic disease and determining its extent. Osseous metastases are generally hematogenously spread, and the vascular bone marrow is usually the earliest site of involvement. For purposes of screening, T1-weighted and STIR image are adequate to detect foci of abnormal marrow. Therefore, MR imaging can be useful in the evaluation of patients suspected of having vertebral metastases with equivocal or negative bone scans. Thanks to its high spatial resolution, MR

imaging may also guide needle biopsy procedures. Plain radiographs are the least sensitive in evaluating the axial skeleton for metastases. Fifty percent of bone mineral content must be altered before evidence of metastases is visible. However, the limitation of MR imaging is the inability to produce 'whole body' images.

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