14 Urothelial Cancer and Transitional Cell Cancer
Epidemiology
Urothelial cancers are more common in men than in women. The incidence of these tumors is increasing. Risk factors include gene abnormalities, chemical exposure, and chronic irritation. No single gene can predict the presence of this tumor, but there are a plethora of genetic abnormalities that occur with this tumor. Chemical exposure to aromatic amines, aniline dyes, tobacco use, and nitrites/nitrates have been associated with the development of bladder cancers. Chronic irritation from indwelling catheters, recurrent urinary tract infections, Schistosoma haematobium, and irradiation have also been noted to be initiating agents. 1 – 4
Pathology
About 95% are transitional cell cancer (TCC) with the other 5% either squamous or adenocarcinoma. Most TCCs occur in the bladder and the remaining 10% in the renal pelvis with fewer than 2% in the ureter.
For bladder cancer, the functional pathology is centered on whether the tumor is confined to the epithelium (stage Ta) or has invaded the lamina proprium (stage T1). These tumors can be managed endoscopically but have a recurrence rate of at least 50% at 5 years. 5
Cytologic Characteristics
G1 = Low grade.
G2 = Intermediate grade.
G3 = High grade.
Genetics
Epidermal growth factor receptor (EGFR), including EGFR1 and EGFR2, and vascular endothelial growth factor (VEGR) are produced by most bladder tumors. The degree of overexpression of these products are indicative of an unfavorable outcome. Since there are targeted drugs to these mutations, inhibition of them may have a tumoricidal effect. The altered expression of p53, p16, and pRB are of no prognostic significance, but the overexpression of human epidermal growth factor receptor 2 (HER2) suggested an inferior response rate to therapy, while EGFR overexpress was associated with an improved response. Additionally, higher levels of VEGF and cyclooxygenase-2 are associated with disease progression. 6 , 7
Staging 8
Tumor
Ta = Noninvasive papillary carcinoma.
T1 = Tumor invades lamina propria only.
T2 = Tumor invades muscularis propria.
pT2a = Tumor invades inner half of superficial muscle.
pT2b = Tumor invades out half of deep muscle.
T3 = Tumor invades perivesical tissue.
pT3a = Invasion is microscopic.
pT3b = Invasion is macroscopic with extravesical mass.
T4 = Invades prostatic stroma, uterus, vagina, pelvis or abdominal wall.
T4a = Invades prostate, uterus, vagina.
T4b = Invades pelvic or abdominal wall.
Lymph Nodes
N1 = Tumor in a single lymph node in primary drainage region.
N2 = Metastasis in multiple lymph nodes in primary drainage region.
N3 = Common iliac lymph node involvement.
Metastases
M0 = No distant metastases.
M1 = Distant metastases.
In patients with bladder cancer, 70% have Ta or T1 disease with 15 to 20% of these progressing to T2 disease. In patients with Ta or T1 disease, 50 to 70% will recur after therapy. If the tumor is G1 or G2 and Ta, there is a lower recurrence rate at 50% and a 5% progression rate. However, in high-risk disease, G3, with T1 or multifocal disease there is a higher recurrence rate at 70% and a 30 to 50% progression rate to T2 or higher. 9 Patients at risk for developing a transition to a higher grade tumor, that is, those with G3 tumors, following treatment with a transurethral resection of bladder tumor (TURBT) are usually treated with intravesical drug therapy. These highly irritating agents, for example, bacillus Calmette–Guérin (BCG), interferon, mitomycin C, and gemcitabine, may cause bladder contracture, dysuria. There has been no conclusive study to validate the use of this technique. 10 – 12
In patients with T1 BCG-refractory disease, a cystectomy is indicated. Patients with G3 T1 disease are often initially treated with a cystectomy due to the high rate of progression through the muscularis propria citing results of a 10-year cancer-specific survival of 80% when this technique is used when the G3 T1 disease is discovered and only 50% when the cystectomy is performed after the tumor has penetrated the muscularis mucosa. 13 , 14
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