II. Epidemiology

  1. Incidence in United States (Sixth most common cancer in the United States)
    1. Men: 50,000 new cases in 2007
    2. Women: 17,000 new cases in 2007
  2. Mortality: 14,000 in 2007 (12th cause of cancer death)
  3. Gender: Men affected more than women by ratio of 3:1
  4. Age: Onset over age 60 in 80% of cases

III. Risk Factors (latency of 5 to 50 years after exposure)

  1. Tobacco abuse (50% of cases in developed countries)
    1. Relative Risk: 4-7 (dose dependent risk)
  2. Occupational exposure to aromatic amines (5-10% of cases in industrialized countries)
    1. Industries
      1. Textile industry
      2. Leather industry
      3. Rubber manufacturing
      4. Paint and Dye manufacturers
      5. Hairdressing chemicals
      6. Organic chemical industries
    2. Compounds
      1. Beta-naphthyl amines
      2. Xenylamine
      3. 4-nitrobiphenyl
      4. Benzidine
  3. Other risks
    1. Arsenic (well water contaminant)
    2. Cyclophosphamide (Cytoxan)
    3. Schistosoma haematobium infection
      1. Endemic to 50 countries in Africa and the Middle East
      2. Predominantly associated with squamous cell cancers
    4. Bladder radiation exposure (e.g. pelvic malignancy treatment)
      1. Onset 5-10 years after treatment
      2. Causes high grade, locally advanced tumors
  4. References
    1. Jankovic (2007) Tumori 93(1): 4-12 [PubMed]

IV. Classification

  1. Epithelial Tumor
    1. Transitional Cell or Urothelial Tumors (90%)
      1. Papilloma (flat or papillary)
      2. Papillary urothelial carcinoma (low to high grade)
      3. Invasive urothelial carcinoma (lamina or detrussor muscle invasion)
    2. Non-urothelial Cell Tumors (9%)
      1. Squamous Cell Carcinoma (verrucous)
      2. Adenocarcinoma (Clear cell, hepatoid, Signet ring, Urachal)
  2. Non-epithelial or Mesenchymal Tumors (1%)
    1. Benign (Hemangioma, Leiomyoma, Lipoma, Neurofibroma)
    2. Malignant (Angiosarcoma, Leiomyosarcoma, histiocytoma, Osteosarcoma, Rhabdomyosarcoma)

V. Symptoms

  1. Painless, microscopic or Gross Hematuria (80%)
    1. Gross blood throughout urination (due to Bladder Cancer in 20% of cases)
    2. Microscopic Hematuria is associated with Bladder Cancer in 2% of cases
  2. Irritative voiding symptoms (20%, typically associated with Bladder Cancer in-situ)
    1. Urinary Frequency
    2. Urinary Urgency
    3. Urge Incontinence
    4. Dysuria
  3. Obstructive symptoms (typically associated with Urethral or Bladder neck tumors)
    1. Decreased stream
    2. Incomplete voiding sense
    3. Straining to evacuate Bladder

VI. Differential Diagnosis

VII. Diagnostics

  1. Urine Cytology
    1. Smear of exfoliated urinary cells
    2. Test Specificity: 95-100%
    3. Test Sensitivity for Bladder Cancer
      1. Overall: <75%
      2. High grade lesions: >80%
      3. Immunocytology: 70-90%
        1. Nuclear matrix protein (bladder Tumor Marker)
      4. Associated with flow cytometry: 93%
  2. Cystoscopy (gold standard)
    1. Fluorescence Cystoscopy
      1. Uses Photosensitizer (e.g. hexaminolevulinic acid instilled intravesically) can help identify flat lesions (e.g. CIS)
    2. Bladder Wash Cytology
      1. Near perfect Test Sensitivity in identifying CIS even with normal appearing mucosa

VIII. Imaging: First line tests

  1. CT Urography and Pelvis CT (preferred)
    1. Has replaced intravenous urography, since it gives both functional and anatomic information
  2. MRI Urography and MRI Pelvis
    1. Indicated when CT contrast is contraindicated

IX. Imaging: Other tests

  1. Intravenous pyelogram
    1. CT Urography has replaced IVP
  2. Renal Ultrasound
    1. Not adequate as a single study to evaluate Bladder Cancer
  3. Bone scan
    1. Obtain if serum Alkaline Phosphatase is elevated or bone metastases suspected
  4. Chest XRay
    1. Indicated as evaluation for metastases

X. Labs: General at time of Bladder Cancer diagnosis

  1. Urinalysis
  2. Complete Blood Count
  3. Basic Chemistry Panel (e.g. Chem8)
  4. Liver Function Tests

XI. Labs: Tumor Markers

  1. Precautions
    1. Despite high sensitivity, not recommended for routine screening due to low Specificity
  2. Available tests
    1. Bladder tumor antigen (BTA) Stat Test or Trak Test
    2. Fluorescence in Situ Hybridization (FISH) Analysis
    3. ImmunoCyt Test
    4. Nuclear matrix Protein 22 (NMP22) test or BladderChek Test

XII. Evaluation

  1. Step 1: Evaluate Hematuria with history, exam and Urinalysis
  2. Step 2: Imaging to characterize lesion (e.g. CT Urography)
  3. Step 3: Consider urine cytology
  4. Step 4: Cystoscopy with biopsy
  5. Step 5: Transurethral Resection of the Bladder
  6. Step 6: Management as below based on tumor type and Bladder staging

XIII. Staging

XIV. Management: Urothelial - Superficial Bladder Cancer (Tis, Ta, T1)

  1. Small, solitary low grade mucosal diploid tumors (Ta)
    1. Indication: Low risk or recurrence
    2. Transurethral resection (consider concurrent single dose of intravesical Chemotherapy with 24 hours of resection)
    3. Surveillance for recurrence
  2. Multifocal, high grade aneuploid tumors (Tis or T1)
    1. Transurethral resection and
    2. Intravesical Immunotherapy 2 hours/week for 6-8 weeks
      1. Bacillus Calmette Guerin (BCG) - preferred
      2. Mitomycin
      3. Doxorubicin
      4. Thiopeta

XV. Management: Urothelial - Invasive Bladder Cancer (T2 to T4)

  1. Radical cystectomy with pelvic lymphadenectomy and
  2. Systemic Chemotherapy
    1. Methotrexate
    2. Vinblastine sulfate
    3. Adriamycin (Doxorubicin)
    4. Cisplatin (Platinol)

XVI. Management: Urothelial - Metastatic Bladder Cancer

  1. Chemotherapy protocol: M-VAC
    1. Methotrexate
    2. Vinblastine sulfate
    3. Adriamycin
    4. Cisplatinum

XVII. Management: Nonurethelial Bladder Carcinoma

  1. Squamous Cell Carcinoma
    1. Cystectomy or Radiation Therapy
  2. Adenocarcinoma
    1. Cystectomy and
    2. Chemotherapy
      1. Consider fluorouracil-based Chemotherapy
      2. Avoid M-VAC (ineffective for adenocarcinoma)
  3. Small Cell Carcinoma
    1. Cystectomy or Radiation Therapy and
    2. Chemotherapy
  4. Mixed Histology
    1. Treat as urothelial cancer as above

XVIII. Prognosis

  1. Worse outcomes for patients continuing Tobacco abuse
    1. Fleshner (1999) Cancer 86:2337-45 [PubMed]
  2. Post-Radical Cystectomy long-term disease-free survival >70% if no extravesical involvement
  3. Metastatic Bladder Cancer (untreated)
    1. Two year survival: <5%

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Ontology: Malignant neoplasm of urinary bladder (C0005684)

Definition (MEDLINEPLUS)

The bladder is a hollow organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It is the sixth most common type of cancer in the United States.

Symptoms include

  • Blood in your urine
  • A frequent urge to urinate
  • Pain when you urinate
  • Low back pain

Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in the workplace. People with a family history of bladder cancer or who are older, white, or male have a higher risk.

Treatments for bladder cancer include surgery, radiation therapy, chemotherapy, and biologic therapy. Biologic therapy boosts your body's own ability to fight cancer.

NIH: National Cancer Institute

Definition (NCI) A primary or metastatic malignant neoplasm involving the bladder.
Concepts Neoplastic Process (T191)
MSH D001749
ICD9 188.9, 188
ICD10 C67 , C67.9
SnomedCT 93689003, 363455001, 269607003, 154540000, 188248005, 399326009
English Malignant neoplasm of bladder, Malig neop bladder NOS, Malign tumor urinary bladder, Malign tumour urinary bladder, Malignant neoplasm of bladder, part unspecified, Malignant neoplasm of urinary bladder NOS, Bladder, unspecified, Malignant neoplasm of bladder, unspecified, Urinary Bladder Cancer, Cancer, Urinary Bladder, BLADDER CANCER, Malig neop of bladder, malignant neoplasm of bladder (diagnosis), bladder cancer, bladder cancer (diagnosis), malignant neoplasm of bladder, Ca bladder, Bladder cancer NOS, Bladder Cancer, Bladder Cancers, Cancer of Bladder, Cancer of the Bladder, malignant tumor of bladder, Malig neo bladder NOS, Cancer of bladder, bladder ca, bladder cancers, cancer of bladder, Cancer, Bladder, Bladder neoplasms malignant, Malignant Tumor of Urinary Bladder, Bladder Ca, Malignant neoplasm of urinary bladder NOS (disorder), Bladder--Cancer, Bladder cancer, CA - Bladder cancer, Malignant tumor of urinary bladder, Malignant tumour of urinary bladder, Malignant tumor of urinary bladder (disorder), cancer of the bladder, urinary bladder cancer, Malignant neoplasm of bladder, NOS, Malignant neoplasm of urinary bladder, Malignant Bladder Neoplasm, Malignant Bladder Tumor, Malignant Neoplasm of Bladder, Malignant Neoplasm of Urinary Bladder, Malignant Neoplasm of the Bladder, Malignant Neoplasm of the Urinary Bladder, Malignant Neoplasm, Bladder, Malignant Neoplasm, Urinary Bladder, Malignant Tumor of Bladder, Malignant Tumor of the Bladder, Malignant Tumor of the Urinary Bladder, Malignant Tumor, Urinary Bladder, Malignant Urinary Bladder Neoplasm, Malignant Urinary Bladder Tumor, Urinary Bladder Malignant Neoplasm, Urinary Bladder Malignant Tumor, Neoplasm malig;bladder, malignant neosplasm of the bladder
Italian Tumori maligni della vescica, Carcinoma della vescica, Tumore maligno di parte non specificata della vescica, Tumore maligno della vescica, Cancro della vescica NAS, Cancro della vescica urinaria, Cancro della vescica
Dutch ca blaas, maligne neoplasma van de blaas, deel niet-gespecificeerd, blaaskanker NAO, maligne neoplasma van de blaas, Maligniteit blaas, Maligne neoplasma van blaas, niet gespecificeerd, blaaskanker, blaasneoplasmata maligne, Maligne neoplasma van blaas
French Carc de la vessie, Cancer de la vessie SAI, Tumeur maligne de la vessie, partie non précisée, Tumeur maligne de la vessie, Cancer de la vessie urinaire, Tumeurs malignes de la vessie, Cancer de la vessie, Cancer vésical, Cancers vésicaux
German boesartige Neubildung der Blase, Ka Blase, Blasenkrebs NNB, boesartige Neubildung der Blase, Teil unspezifisch, Krebs der Blase, Harnblasenkrebs, Boesartige Neubildung der Harnblase, Boesartige Neubildung: Harnblase, nicht naeher bezeichnet, Neubildungen der Blase boesartig, Blasenkrebs, Krebs der Harnblase
Portuguese Neoplasia maligna da bexiga parte NE, Ca da bexiga, Cancro da bexiga NE, Neoplasia maligna da bexiga, Neoplasias malignas da bexiga, Cancro da bexiga, Câncer da Bexiga
Spanish Ca de vejiga, Neoplasia maligna de vejiga, Cáncer de vejiga NEOM, Neoplasia maligna de vejiga, parte no especificada, neoplasia maligna de la vejiga (trastorno), neoplasia vesical maligna, neoplasia maligna de la vejiga, neoplasia maligna de vejiga urinaria, SAI (trastorno), neoplasia maligna de vejiga urinaria, SAI, tumor maligno de vejiga (trastorno), tumor maligno de vejiga, Neoplasias malignas de vejiga, Cáncer de vejiga, Cáncer de la Vejiga
Japanese 膀胱の悪性新生物、部位不明, 膀胱癌NOS, 悪性膀胱新生物, 膀胱の悪性新生物, 膀胱癌, ボウコウガン, ボウコウガンNOS, ボウコウノアクセイシンセイブツ, アクセイボウコウシンセイブツ, ボウコウノアクセイシンセイブツブイフメイ
Czech Maligní novotvar močového měchýře, část blíže neurčená, Novotvary močového měchýře maligní, Maligní nádorové onemocnění močového měchýře, Ca močového měchýře, Maligní nádor močového měchýře NOS, Maligní novotvar močového měchýře, močový měchýř - rakovina, rakovina močového měchýře
Korean 방광의 악성신생물, 상세불명 방광의 악성신생물
Hungarian Húgyhólyag nem meghatározott részének malignus daganata, Húgyhólyag carcinoma, Húgyhólyag neoplasmák, rosszindulatú, Húgyhólyag rák, Húgyhólyag malignus daganata, Húgyhólyag rák k.m.n.
Norwegian Blærekreft, Kreft i urinblære, Blærecancer, Cancer i urinblære