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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

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


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



• Physical trauma to the urothelium


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


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


Risk Factors

• Cigarette smoking



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


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


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


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


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


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


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%)


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


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


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


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


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


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


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


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).


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.


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


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)


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.


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


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


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


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


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
