bladder carcinomas

Bladder Carcinomas

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

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Risk Factors

• Cigarette smoking

• Occupational exposure

• Management with cyclophosphamide(Cytoxan)

• Physical trauma to the urothelium

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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

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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

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Risk Factors

• Cigarette smoking

• Occupational exposure

• Management with cyclophosphamide(Cytoxan)

• Physical trauma to the urothelium – Infection, instrumentation, calculi

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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

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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

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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

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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

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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

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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%)

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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

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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

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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

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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

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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

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Laboratory FindingsB 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

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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

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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).

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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.

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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

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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)

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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.

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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

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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

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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

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http://www.webmd.com/cancer/bladder-cancer/cystectomy-for-bladder-cancerhttp://www.healthline.com/images/staywell/36680.jpg

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

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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

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