Bladder Cancer and Upper Tracts

Chapter 19 Bladder Cancer and Upper Tracts





Epidemiology And Risk Factors



Epidemiology


Bladder cancer is the most common tumor of the urinary tract. In the United States, it is the fourth most common malignancy in males, accounting for 7% of all male malignancies. There will be an estimated 70,530 new cases and 14,680 deaths from bladder cancer in the United States in 2010.1 The peak incidence is in the ninth decade, although there is a suggestion of a trend toward presentations at a younger age. The incidence is four times higher in men than in women. The lifetime risk for men is 3.8% and for women is 1.2%.1 The tumor is twice as common in whites as in African Americans. In the United Kingdom, bladder cancer is overall the seventh most common malignancy, with an age-standardized rate of 11.4 per 100,000.2


The incidence of upper tract disease is less easily estimated because cancer registries tend to include primary PC system tumors as “renal” cancers. If one makes the assumption that 15% of such “renal” tumors are of PC system origin, there will be 8740 new cases and 1960 deaths from renal pelvic cancer in the USA in 2010.1 There will be an estimated 2490 new cases and 830 deaths from ureteric cancer in the United States in 2010.1 Ureteral transitional cell cancer (TCC), like bladder cancer, is more common in men than in women (ratio 2:1), and the incidence peaks in the eighth decade of life.


For patients with a bladder cancer, up to 6.4% will develop upper tract tumors.3,4 Conversely, for patients with upper tract tumors, up to 40% will develop lower tract disease.5



Risk Factors


Reported risk factors for urothelial tumors include exposure to aniline, aromatic amines, diesel fumes, phenacetin abuse, cigarette smoking, arsenic, and living in urban areas. Heavy smokers (>40 pack-yr) are five times more prone to develop TCC than nonsmokers.6 Balkan nephropathy, an endemic degenerative interstitial nephropathy in Eastern Europe of unknown etiology, is associated with 100 to 200 times the risk of upper tract TCC. These tumors are typical multifocal, but of low grade.7,8 Coffee drinking and artificial sweeteners have been considered to be possible risk factors, but these have not been fully substantiated as a cause of this malignancy.9


Genetic factors in the etiology of urothelial tumors are emerging, and these may be associated with the aggressiveness of the tumor, such as tumor grade, stage, and propensity for vascular invasion.10


Worldwide, squamous cell carcinomas are the most common histology and are associated with chronic inflammation, for example, chronic urinary tract infection or calculi and schistosomiasis (Schistosoma haematobium). Squamous cell carcinomas are the most common type of cancers affecting the urethra in both males and females. However, in industrialized countries such as the United States where chemical exposure and tobacco use are more prevalent, TCCs are the most frequent histology.


Adenocarcinomas of the bladder mucosa are associated with a persistent urachal remnant and cystitis glandularis (which is associated with bladder extrophy).11 In addition, micropapillary and small cell tumors have been reported and are signs of an aggressive histology associated with worse outcomes, likely as a result of early micrometastases.12,13 The rarity of these two histologies has limited our abilities to determine definitive associations; their frequent finding in combination with TCCs would lead one to expect an association with carcinogen exposure.



Anatomy and Pathology


The urinary collecting system conveys, stores, and delivers urine to the exterior of the body; it extends from the renal collecting system and calyces, renal pelvis, ureter, bladder, and urethra. The epithelium of the entire collecting system, the urothelium, consists of the same cell type, transition cells. Deep to the urothelium is a layer of connective tissue and irregularly arranged smooth muscle fibers, frequently considered the submucosa (although strictly this term is incorrect because there is no muscularis mucosae). Deep to the submucosa are three layers of muscle (internal or superficial longitudinal, middle circular, and external or deep longitudinal). Deep to all of these layers is the perivesical or periureteral fat or, toward the dome of the bladder, a partial serous coat derived from the peritoneum (Figure 19-1A).



The bladder develops from the primitive urogenital sinus, which in utero has a communication with the umbilicus via the allantois. The latter normally involutes by the time of birth into a thick fibrous cord, the urachus, that connects the dome (or apex) of the bladder with the umbilicus. When undistended, the muscles of the bladder bunch together to form a rugose pattern internally; this becomes flatter with increasing bladder distention.


In adult males, chronic bladder outflow obstruction from prostatic hypertrophy commonly leads to hypertrophy of the bladder wall musculature and trabeculation. Outpouchings of mucosa, or diverticulae, may also develop.


The vast majority of tumors that affect the urinary collecting system are epithelial in origin and are termed urothelial carcinomas. The vast majority of these tumors are of TCC origin (>90%); other subtypes are squamous cell (5-10%), adenocarcinoma (2-3%), and small cell carcinoma (<1%).11 TCCs have a propensity to develop in multiple locations throughout the urothelium, both upper tracts and lower tracts. Adenocarcinomas may be mucin-secreting.


Other extremely rare tumors include leiomyoma, hemangioma, granular cell tumors, neurofibroma, paraganglioma, pheochromocytoma, leiomyosarcoma, rhabdomyosarcoma, hematopoietic and lymphoid tumors (e.g., non-Hodgkin’s lymphoma), carcinosarcoma, malignant melanoma, metastases, and direct invasion from adjacent organs.11






Patterns of Tumor Spread



Bladder


Bladder urothelial tumors may invade progressively through the bladder wall (i.e., lamina propria, superficial muscle, deep muscle) and eventually to extravesical structures. In advanced local disease, tumor may extend to involve adjacent structures, such as the rectum, anterior abdominal wall, pelvic side wall muscles (e.g., the obturator internus) and bones (e.g., the iliac and pubic bones). The bladder has an extraperitoneal (inferior) and an intraperitoneal (superior) component. If disease extends into the latter, dissemination can occur within the peritoneal cavity, resulting in widespread peritoneal implants and ascites.


Disease may spread lymphatically, typically in a contiguous fashion from pelvic (internal iliac, obturator, and external iliac) to common iliac and retroperitoneal nodes. In advanced disease, lymphatic spread may extend above the diaphragm to mediastinal, hilar, and cervical nodes. The incidence of nodal metastasis is approximately 30% in tumors that involve the bladder wall and approximately 60% in those with extravesical invasion.17 Nodal staging has an important impact on prognosis.


The tumor may also metastasize hematogenously, with the liver being the most common site for metastatic disease, followed by bones and lungs.18


The risk for lymphatic and/or hematogenous spread increases with increasing tumor size and stage (see later), and the incidence of distant metastases increases with increasing tumor (T) and node (N) stages.


Urothelial disease in the bladder neck may extend into the urethra. Urethral disease may involve adjacent structure, including the vaginal wall and the corpora of the penis. In males, TCC involving the urethra is commonly found in the prostatic urethra, where it may invade locally into the prostate gland itself.


Urachal tumors, because they arise from the remnant urachus that extends from the dome of the bladder to the umbilicus, have a propensity to spread within the peritoneal cavity and may also involve the anterior abdominal wall.


When seen, in males, TCC of the urethra is commonly found in the prostatic urethra.




Staging Evaluation



Bladder


The two main staging classification systems for tumors are (1) the tumor-node-metastasis (TNM; Tables 19-1 and 19-2) and (2) the Jewett-Strong-Marshall classification (Table 19-3). The TNM staging system is the more widely used and comprehensive. T stage mainly describes the depth of local bladder wall invasion of the tumor as related to normal bladder wall layers. N stage is based on the size and number of nodes involved by metastatic disease. M stage describes whether there are disseminated hematogenous metastases or not. Retroperitoneal adenopathy is classified as M stage disease.


Table 19-1 Tumor-Node-Metastasis Staging for Bladder Cancer by the American Joint Committee on Cancer


































































STAGE DISEASE EXTENT
T Stage
Ta Noninvasive papillary carcinoma, confined to urothelium and projecting toward lumen
Tis Carcinoma in situ: flat tumor, high-grade histologic features confined to urothelium
T1 Tumor invades subepithelial connective tissue (lamina propria)
T2 Tumor invades muscle
    T2a Tumor invades superficial muscle (inner half)
    T2b Tumor invades deep muscle (outer half)
T3 Tumor invades perivesical tissue
    T3a Tumor invades perivesical tissue microscopically
    T3b Tumor invades perivesical tissue macroscopically (extravesical mass)
T4 Tumor invades prostate, uterus, vagina, pelvic wall, or abdominal wall
    T4a Tumor invades prostate, uterus, or vagina
    T4b Tumor invades pelvic wall or abdominal wall
N Stage
N0 No regional lymph node metastases
N1 Metastasis to single lymph node < 2 cm in greatest dimension
N2 Metastasis to single lymph node 2-5 cm in greatest dimension or multiple lymph nodes none > 5 cm in greatest dimension
N3 Metastasis in a lymph node > 5 cm in greatest dimension
M Stage
M0 No distant metastases
M1 Distant metastases

Suffix “is,” associated carcinoma in situ; suffix “m,” multiple tumors.


From Bladder cancer. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010:569-577.


Table 19-2 Staging for Bladder Cancer, with Tumor-Node-Metastasis Equivalent































STAGE DISEASE EXTENT TNM CLOSEST EQUIVALENT
0a Papillary, noninvasive Ta, N0, M0
0is Carcinoma in situ, noninvasive Tis, N0, M0
I Invades subepithelial connective tissue T1, N0, M0
II Invades muscle layer T2, N0, M0
III Extravesical spread T3 or T4a, N0, M0
IV Fixed to or invading prostate, uterus, vagina or pelvic lymph nodes T4b, N0, M0
or any T, N1 to 3, M0,
or any T, any N, M1

TNM, tumor-node-metastasis.


From Bladder cancer. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010:569-577.


Table 19-3 Comparison of AJCC and Jewett-Strong-Marshall Staging Systems



































STAGE DISEASE EXTENT TNM CLOSEST EQUIVALENT
0 Limited to mucosa, flat in situ or papillary Tis, Ta
A Lamina propria invaded T1
B1 < halfway through muscularis T2a
B2 > halfway through muscularis T2b
C Perivesical fat, prostate, uterus or vagina, pelvic wall or abdominal wall T3, T4a, T4b
D1 Pelvic lymph node(s) involved N1-N3
D2 Distant metastases M1

TNM, tumor-node-metastasis.


From National Cancer Institute. Surveillance, Epidemiology, and End Results Program. SEER Training Modules Staging: Comparison of AJCC & Jewell-Strong-Marshall Staging Systems. Available at http://training.seer.cancer.gov/bladder/abstract-code-staging.html (accessed October 27, 2011).


A schematic of the TNM T staging is presented in Figure 19-1A and B. Superficial tumors are considered Tis, Ta, and T1; infiltrative tumors are T2, T3, and T4.21,22


Prognosis worsens with increasing T, N, and M stage and higher classes of Jewett-Strong-Marshall staging. The overall 5-year survival is 97.2%, 74.3%, 36.2%, and 5.8%, for in situ, localized, regional, and distant disease, respectively.23 Nodal status and organ confinement are independent predictors of survival.24


Urothelial tumors may develop in the bladder diverticulae. Urothelial tumors may also arise or involve the prostatic urethra. Both of these have a poorer prognosis, the former because there is no muscle layer to act as a barrier to tumor spread.


Prognosis is also affected by tumor grade, the presence of vascular and lymphatic invasion, and diffuse carcinoma in situ (CIS). Of note, these latter factors are not currently reflected in staging classifications.25


Treatment options are influenced by tumor stage. Clinical staging can underestimate the extent of disease in up to 50% of cases as compared with pathology.25 Imaging has the potential to improve this.



Upper Tracts


The TNM staging system for urothelial tumors of the upper tracts is presented in Tables 19-4 and 19-5. As with bladder staging, T staging of the upper tracts is assessed in


Table 19-4 Tumor-Node-Metastasis Staging of Upper Urinary Tract Transitional Cell Carcinoma










































TNM STAGE DISEASE EXTENT
Ta Noninvasive papillary carcinoma, confined to urothelium and projecting toward lumen
Tis Carcinoma in situ: flat tumor, high-grade histologic features but confined to urothelium
T1 Tumor invades subepithelial connective tissue (lamina propria)
T2 Tumor invades muscularis
T3 Renal pelvis: Tumor invades beyond muscularis into peripelvic fat or renal parenchyma.
Ureter: Tumor invades beyond muscularis into periureteric fat
T4 Tumor invades adjacent organs, pelvic or abdominal wall, or through kidney into perinephric fat
N0 No regional lymph node metastases
N1 Metastasis to single lymph node < 2 cm in greatest dimension
N2 Metastasis to single lymph node 2-5 cm in greatest dimension, or multiple lymph nodes, none > 5 cm in greatest dimension
N3 Metastasis in a lymph node > 5 cm in greatest dimension
M0 No distant metastasis
M1 Distant metastases

TNM, tumor-node-metastasis.


From Renal pelvis & ureter. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010:561-567.




relation to depth of invasion into the various layers of the wall of the ureter (see Figure 19-1C).



Imaging


There are currently no established primary screening programs for the detection of urothelial tumors. The majority of tumors are detected in the course of investigation for one of the previously discussed presenting symptoms. Primary lower tract tumors are typically detected by and evaluated cystoscopy, and primary upper tract tumors are typically detected by some form of imaging.



Primary Tumor (T)



Bladder


In low T stage disease, cystoscopy and deep biopsy with histologic evaluation is the standard of care. For more deeply invasive tumors (stage T3, T4), clinical staging, which includes bimanual examination under anesthesia to assess the bladder mass and fixity to adjacent organ, has reported errors of both under- and overstaging, of 25% to 50%.2629 Imaging plays a role in the evaluation of such tumors, especially for nodal and hematogenous metastatic disease.


Tumors in narrow neck diverticulae may escape cystoscopic detection, for which imaging may be able to make a contribution. Computed tomography (CT) is the mainstay for staging in these tumors, but magnetic resonance imaging (MRI) has the additional advantages of better tissue contrast resolution and direct multiplanar capability.



Computed Tomography




Findings

Urothelial tumors in the bladder may appear as foci of thickening in the wall or as filling defects, which may be polypodial (Figure 19-2). Fine calcification may be seen on the mucosal surface. The lesions may demonstrate early enhancement after IV contrast media infusion, probably a reflection of angiogenic activity in the tumor (Figure 19-3). CT is unable to resolve the various bladder wall layers and is, therefore, unable to resolve low T stage disease. Retraction of the outer bladder wall at the site of the tumor is suggestive of deep muscle involvement (stage T2b).




Stage T3b disease is suggested by irregularity and loss of definition of the outer bladder wall and/or nodules and stranding in the perivesical fat. T3a (microscopic perivesical) disease cannot be detected.


Evaluation of stage T4 disease, with adjacent organ involvement, is better undertaken by MRI than by CT because of the limitations of contrast resolution and acquisition plane of CT.


Tumors close to the vesicoureteric junction may cause ureteric obstruction, which may be a presenting feature of the disease (Figure 19-4). Tumors may also be detected in bladder diverticulae, which importantly may not be visible on cystoscopy (Figure 19-5).





Magnetic Resonance Imaging




Findings

The signs of bladder tumors are similar to those on CT. Tumors are usually hyperintense to muscle on T2-weighted images and isointense to muscle on T1-weighted images (Figure 19-6A). On occasion, the combination of T2-weighted and contrast-enhanced T1 weighted images can help to delineate between stages T2a and T2b tumors, with preservation of T2-weighted hypointensity of bladder muscle adjacent to enhancing tumor.



The corresponding findings of T3b disease described previously for CT appear as hypointense nodules or stranding within the T1-weighted and T2-weighted hyperintense perivesical fat (see Figure 19-6A). These findings may be more conspicuous with the use of contrast-enhanced T1-weighted fat-suppressed images, in which enhancing tissue is seen in the surrounding hypointense (suppressed) perivesical fat.30


MRI is superior to CT in staging T4 disease because of its better intrinsic contrast resolution and multiplanar capability. For example, the combination of sagittal and axial images on MRI allows good delineation of the rectum and vagina (see Figure 19-6B). It should be noted that abutment of structures does not necessarily indicate invasion, and conversely, involvement cannot be excluded; invasion is more likely if foci of infiltration can be identified.


Overall, studies of CT and MRI suggest that MRI is more accurate in staging with accuracies ranging from 73% to 96% compared with CT accuracies of 40% to 95%. This is largely because of the superior ability of MRI in assessing deep muscle layer involvement and earlier detection of adjacent organ invasion. It should be noted that most reported MRI evaluations have been undertaken with body and not pelvic phase array coils, and MRI accuracy may be improved further with such higher-resolution coils.17,3149

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Mar 6, 2016 | Posted by in GENERAL RADIOLOGY | Comments Off on Bladder Cancer and Upper Tracts

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