Bladder Carcinomas

Incidence Risk factors Staging Histopathology – Papilloma – Transitional Cell Carcinoma – Nontransitional Cell Carcinoma Adenocarcinoma Squamous cell carcinoma Undifferentiated carcinomas Mixed carcinoma – Rare epithelial and nonepithelial cancers Clinical Findings Treatment

Incidence The second most common cancer of the genitourinary tract Accounts for 7% of new cancer cases in men Accounts for 2% of new cancer cases in women Average age at diagnosis is 65 years – 75% of bladder cancers localized to the bladder – 25% have spread to regional lymph nodes or distant sites B L A D D E R C A R C I N O M A

Risk Factors Cigarette smoking Occupational exposure Management with cyclophosphamide(Cytoxan) Physical trauma to the urothelium B L A D D E R C A R C I N O M A

Risk Factors Cigarette smoking – 50% of cases in men – 31% of cases in women – Confers a twofold increased risk of bladder cancer than nonsmokers; dose-related – Causative agents: alpha- and beta-naphthylamine  secreted into the urine of smokers Occupational exposure Management with cyclophosphamide(Cytoxan) Physical trauma to the urothelium B L A D D E R C A R C I N O M A

Risk Factors Cigarette smoking Occupational exposure – 15–35% of cases in men – 1–6% of cases in women – Increased risk: workers in the chemical, dye, rubber, petroleum, leather, and printing industries – Specific occupational carcinogens include benzidine, betanaphthylamine, and 4-aminobiphenyl – Latency period may be prolonged Management with cyclophosphamide(Cytoxan) Physical trauma to the urothelium – Infection, instrumentation, calculi B L A D D E R C A R C I N O M A

Risk Factors Cigarette smoking Occupational exposure Management with cyclophosphamide(Cytoxan) Physical trauma to the urothelium – Infection, instrumentation, calculi B L A D D E R C A R C I N O M A

Staging Nodal (N) stage Nx – cannot be assessed N0 – no nodal metastases N1 – single node <2 cm involved N2 – single node involved 2– 5cm in size or multiple nodes none >5 cm N3 – one or more nodes >5cm in size involved Metastases (M) stage Mx – cannot be defined M0 – no distant metastases M1 – distant metastases present B L A D D E R C A R C I N O M A

Histopathology Papilloma Transitional Cell Carcinoma Nontransitional Cell Carcinoma – Adenocarcinoma – Squamous cell carcinoma – Undifferentiated carcinomas – Mixed carcinoma Rare epithelial and nonepithelial cancers – Villous adenomas, carcinoid tumors, carcinosarcomas, melanomas – Pheochromocytomas, lymphomas, choriocarcinomas, and various mesenchymal tumors B L A D D E R C A R C I N O M A

Papilloma Papillary tumor with a fine fibrovascular stalk supporting an epithelial layer of transitional cells with normal thickness and cytology Rare benign condition Usually occurs in younger patients B L A D D E R C A R C I N O M A

Transitional Cell Carcinoma 90% of all bladder cancers Most commonly appear as papillary, exophytic lesions – Superficial Less commonly, may be sessile or ulcerated – Often invasive Carcinoma in situ (CIS) – flat, anaplastic epithelium – Urothelium lacks the normal cellular polarity, and cells contain large, irregular hyperchromatic nuclei with prominent nucleoli B L A D D E R C A R C I N O M A

Nontransitional Cell Carcinoma: Adenocarcinoma <2% of all bladder cancers 2 types: – Primary adenocarcinomas of the bladder Preceded by cystitis and metaplasia Often arise along the floor of the bladder – Adenocarcinomas arising from the urachus Occur at the dome – Both tumor types are often localized at the time of diagnosis, but muscle invasion is usually present Histology: mucus-secreting and may have glandular, colloid, or signet-ring patterns Five-year survival: <40%, despite aggressive surgical management B L A D D E R C A R C I N O M A

Nontransitional Cell Carcinoma: Squamous cell carcinoma 5% -10% of all bladder cancers in the US History of: – Chronic infection – Vesical calculi – Chronic catheter use – Bilharzial infection owing to Schistosoma haematobium (60%) B L A D D E R C A R C I N O M A

Nontransitional Cell Carcinoma: Undifferentiated carcinomas Rare (<2%) No mature epithelial elements Very undifferentiated tumors with neuroendocrine features and small cell carcinomas tend to be aggressive and present with metastases B L A D D E R C A R C I N O M A

Nontransitional Cell Carcinoma: Mixed carcinomas 4–6% of all bladder cancers Composed of a combination of transitional, glandular, squamous, or undifferentiated patterns Most common type comprises transitional and squamous cell elements Most are large and infiltrating at the time of diagnosis B L A D D E R C A R C I N O M A

Rare Epithelial and Nonepithelial Cancers Rare epithelial cancers: villous adenomas, carcinoid tumors, carcinosarcomas, melanomas Rare nonepithelial cancers: pheochromocytomas, lymphomas, choriocarcinomas, and various mesenchymal tumors Cancers of the prostate, cervix, and rectum may involve the bladder by direct extension Most common tumors metastatic to the bladder include (in order of incidence) – Melanoma, lymphoma, stomach, breast, kidney, lung and liver B L A D D E R C A R C I N O M A

Signs and symptoms Hematuria (85–90%) – Gross or microscopic, intermittent rather than constant Vesical irritability – Frequency, urgency, and dysuria Irritative voiding symptoms – More common in patients with diffuse CIS Symptoms of advanced disease: – Bone pain from bone metastases or – Flank pain from retroperitoneal metastases or ureteral obstruction B L A D D E R C A R C I N O M A

Laboratory Findings Urinalysis – Hematuria; may be accompanied by pyuria – Azotemia in patients with ureteral occlusion (primary bladder tumor or lymphadenopathy) CBC – Anemia (chronic blood loss, or replacement of the bone marrow with metastatic disease) Urinary cytology – Voided urine: exfoliated cells from both normal and neoplastic urothelium – Barbotage: larger quantities of cells can be obtained by gently irrigating the bladder with isotonic saline solution through a catheter or cystoscope B L A D D E R C A R C I N O M A

Laboratory Findings B L A D D E R C A R C I N O M A

Imaging Uses: – To evaluate the upper urinary tract – To assess the depth of muscle wall infiltration in infiltrating bladder tumors – To detect the presence of regional or distant metastases Intravenous urography – One of the most common imaging tests for the evaluation of hematuria Computed tomography (CT) urography – More accurate for evaluation of the entire abdominal cavity, renal parenchyma, and ureters in patients with hematuria – Largely replaces intravenous pyelography – Bladder tumors: pedunculated, radiolucent filling defects projecting into the lumen; nonpapillary, infiltrating tumors may result in fixation or flattening of the bladder wall B L A D D E R C A R C I N O M A

Imaging CT and magnetic resonance imaging (MRI) – Characterize the extent of bladder wall invasion – Detect enlarged pelvic lymph nodes – Overall staging accuracy ranging from 40% to 85% for CT and from 50% to 90% for MRI ( – Rely on size criteria for the detection of lymphadenopathy: LN >1 cm = metastases Chest X-Ray – Metastasis to the lungs Radionuclide bone scan – Metastasis to the bones – Can be avoided if the serum alkaline phosphatase is normal B L A D D E R C A R C I N O M A

Image of the urinary bladder obtained on an intravenous urogram. The filling defect represents a papillary bladder cancer.

MRI scan of invasive bladder carcinoma: A: T1-weighted image; B: T2-weighted image. Bladder wall invasion is best assessed on T2-weighted images because of heightened contrast between tumor (asterisks) and detrusor muscle along with ability to detect interruption of the thin high-intensity line representing normal bladder wall. The heterogeneous appearance of the prostate (arrow) on the T2-weighted image owes to benign prostatic hypertrophy, confirmed at cystectomy.

Cystouretheroscopy and Tumor Resection The diagnosis and initial staging of bladder cancer is made by cystoscopy and transurethral resection (TUR). B L A D D E R C A R C I N O M A

Cystouretheroscopy and Tumor Resection Once a tumor is visualized or suspected, the patient is scheduled for examination under anesthesia and transurethral resection (TUR) or biopsy of the suspicious lesion. The objectives are tumor diagnosis, assessment of the degree of bladder wall invasion (staging), and complete excision of the low-stage lesions amenable to such treatment. B L A D D E R C A R C I N O M A

transurethral resection (TUR)

Treatment Principles Initial low-grade small tumors  low risk of progression – TUR alone followed by surveillance or intravesical chemotherapy T1, high-grade, multiple, large, recurrent tumors or those associated with CIS on bladder biopsies  higher risk of progression and recurrence – Intravesical chemotherapy or immunotherapy after complete and careful TUR B L A D D E R C A R C I N O M A

Treatment Principles T2, T3, more invasive, but still localized, tumors – More aggressive local treatment, including partial or radical cystectomy – Combination of radiation and systemic chemotherapy Unresectable local tumors (T4B) are candidates for – Systemic chemotherapy, followed by surgery (or possibly irradiation) B L A D D E R C A R C I N O M A

Treatment: Intravesical Chemotherapy Immunotherapeutic or chemotherapeutic agents instilled into the bladder directly via catheter Avoids the morbidity of systemic administration Most common agents in the US are mitomycin C, thiotepa, and Bacillus Calmette-Guérin (BCG) Unable to reach cancer cells: – that have grown deeply into the bladder wall – in the kidneys, ureters, and urethra, or in other organs Used only for noninvasive (stage 0) or minimally invasive (stage I) bladder cancers. B L A D D E R C A R C I N O M A

Treatment: Surgery Transurethral resection – Initial form of treatment for all bladder cancers – Allows a reasonably accurate estimate of tumor stage and grade and the need for additional treatment – Patients with single, low-grade, noninvasive tumors may be treated with TUR alone B L A D D E R C A R C I N O M A

Treatment: Surgery Partial Cystectomy – Removal of a part of the bladder – For patients with solitary, infiltrating tumors (T1– T3) localized along the posterior lateral wall or dome of the bladder – For patients with cancers in a diverticulum B L A D D E R C A R C I N O M A

Treatment: Surgery Radical Cystectomy – Removal of the entire bladder, nearby lymph nodes (lymphadenectomy), part of the urethra, and nearby organs that may contain cancer cells. – In men: prostate, seminal vesicles, and part of the vas deferens – In women: cervix, uterus, ovaries, fallopian tubes, and part of the vagina – The “gold standard” of treatment for patients with muscle invasive bladder cancer B L A D D E R C A R C I N O M A

Treatment: Radiotherapy External beam irradiation (5000–7000 cGy), delivered in fractions over a 5- to 8-week period, is an alternative to radical cystectomy in well-selected patients with deeply infiltrating bladder cancers B L A D D E R C A R C I N O M A

Treatment: Chemotherapy Early results with single chemotherapeutic agents and, more recently, combinations of drugs have shown that a significant number of patients with metastatic bladder cancer respond partially or completely – Regional or distant metastases: 15% – With invasive disease: 30–40% develop distant metastases despite radical cystectomy or definitive radiotherapy B L A D D E R C A R C I N O M A