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Incidence in United States (Sixth most common cancer in the United States)
- New cases in 2017 (estimated): 79,030
- Mortality: 16,400 in 2016 (12th cause of cancer death)
- Bladder Cancer mortality is decreasing in women, but not men (as of 2017)
- Gender: Men affected more than women by ratio of 3-4 to 1
- Age: Onset over age 55 years in 90% of cases (mean age 73 years)
- Race
- Twice as common in white patients
- Delayed diagnosis more common in black patients
- References
- NIH Cancer Statistics
- https://seer.cancer.gov/statfacts/html/urinb.html
- Risk Factors (latency of 5 to 50 years after exposure)
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Tobacco Abuse (50% of cases in developed countries)
- Relative Risk: 4-7 (dose dependent risk)
- Occupational exposure to aromatic amines (5-10% of cases in industrialized countries)
- Industries
- Textile industry
- Leather industry
- Rubber manufacturing
- Paint and Dye manufacturers
- Hairdressing chemicals
- Organic chemical industries
- Compounds
- Beta-naphthyl amines
- Xenylamine
- 4-nitrobiphenyl
- Benzidine
- Higher risk exposures
- Arsenic (well water contaminant)
- Cyclophosphamide (Cytoxan)
- Schistosoma haematobium infection
- Endemic to 50 countries in Africa and the Middle East (farmers are high risk)
- Predominantly associated with squamous cell cancers
- Bladder radiation exposure (e.g. pelvic malignancy treatment, CT Pelvis in childhood)
- Onset 5-10 years after treatment
- Causes high grade, locally advanced tumors
- Other exposure associations
- Aristolochia herbal preparations
- Processed red meat ingestion
- Phenacetin (before U.S. FDA ban in 1983, was in APC, with Aspirin and Caffeine)
- Pioglitzaone (Actos) use for more than 1 year
- Medical condition associations
- Family History of Bladder Cancer (esp. young age onset)
- Diabetes Mellitus
- Human Papillomavirus Infection
- Obesity
- Renal Transplant recipient
- Chronic Bladder inflammation
- Chronic Kidney Stones and Bladder stones
- Chronic Urinary Tract Infections
- Longterm indwelling Urinary Catheter
- References
- Jankovic (2007) Tumori 93(1): 4-12 [PubMed]
- Cancer.Net Bladder Cancer Risk Factors (ASCO)
- http://www.cancer.net/cancer-types/bladder-cancer/risk-factors
- Epithelial Tumor (99%)
- Transitional Cell or Urothelial Tumors (90%)
- Papilloma (flat or papillary)
- Papillary urothelial carcinoma (low to high grade)
- Invasive urothelial carcinoma (lamina or detrussor Muscle invasion)
- Non-urothelial Cell Tumors (9%)
- Squamous Cell Carcinoma (verrucous)
- Uncommon in developed world
- Represents 81% of Bladder Cancer cases where Schistosomiasis is endemic
- Adenocarcinoma (Clear cell, hepatoid, Signet ring, Urachal)
- Small Cell Carcinoma
- Non-epithelial or Mesenchymal Tumors (1%)
- Benign (Hemangioma, Leiomyoma, Lipoma, Neurofibroma, Paraganglioma)
- Malignant (Angiosarcoma, Leiomyosarcoma, fibrous histiocytoma, Osteosarcoma, Rhabdomyosarcoma)
- Painless, microscopic or Gross Hematuria (80%)
- Gross blood throughout urination (due to Bladder Cancer in 20% of cases)
- Microscopic Hematuria is associated with Bladder Cancer in 2% of cases
- Irritative voiding symptoms (20%, typically associated with Bladder Cancer in-situ)
- Urinary Frequency
- Urinary Urgency
- Urge Incontinence
- Dysuria
- Obstructive symptoms (typically associated with Urethral or Bladder neck tumors)
- Decreased stream
- Incomplete voiding sense
- Straining to evacuate Bladder
- Metastatic disease symptoms
- Anorexia or Cachexia
- Respiratory symptoms
- Abdominal Pain, Pelvic Pain or Flank Pain
- Acute Renal Failure with edema
- Bone pain
- Urine Cytology
- Indications
- High risk for urothelial tumors
- Known urothelial carcinoma
- Avoid in isolated asymptomatic Microscopic Hematuria (higher False Positive Rate)
- Smear of exfoliated urinary cells
- Test Specificity: 95-100%
- However, False Positives with Renal Calculi and Urinary Tract Infections
- Test Sensitivity for Bladder Cancer
- Overall: <75%
- Negative findings do not exclude Bladder Cancer
- High grade urothelial tumors: >80-90%
- Immunocytology: 70-90%
- Nuclear matrix Protein (bladder Tumor Marker)
- Associated with flow cytometry: 93%
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Cystoscopy (gold standard)
- Indications
- Gross Hematuria
- Microscopic Hematuria AND one of the following criteria
- Age >35 years old OR
- Bladder Cancer risk factors (e.g. Tobacco Abuse, chemical exposures, irritative Bladder symptoms)
- Fluorescence Cystoscopy
- Uses Photosensitizer (e.g. hexaminolevulinic acid instilled intravesically) can help identify flat lesions (e.g. CIS)
- Bladder Wash Cytology
- Near perfect Test Sensitivity in identifying CIS even with normal appearing mucosa
- Transurethral resection of the Bladder tumor (TURBT)
- Abdominal CT or MRI imaging should be completed prior to TURBT (False Positives from procedure)
- Indicated for abnormal Bladder wash cytology or tissue pathology
- Visible tumor removed and surrounding tissue sampled for diagnosis, staging, grading
- Multiphasic CT Urography and Pelvis CT with and without contrast (preferred)
- Has replaced intravenous urography, since it gives both functional and anatomic information
- High upper tract lesion Test Sensitivity (95%) and Test Specificity (92%)
- MRI Urography and MRI Pelvis
- Indicated when CT contrast is contraindicated (pregnancy, contrast allergy, Renal Insufficiency)
- Intravenous pyelogram
- CT Urography has replaced IVP
- Renal Ultrasound
- Consider in addition to CT or MRI in suspected renal parenchymal disease
- Not adequate as a single study to evaluate Microscopic Hematuria or Bladder Cancer (low Test Sensitivity)
- Bone scan
- Obtain if Serum Alkaline Phosphatase is elevated or bone metastases suspected
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Chest XRay
- Indicated as evaluation for metastases
- Labs
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General at time of Bladder Cancer diagnosis
- Precautions
- Despite high sensitivity, not recommended for routine screening due to low Specificity
- Available tests
- Bladder tumor Antigen (BTA) Stat Test or Trak Test
- Fluorescence in Situ Hybridization (FISH) Analysis
- ImmunoCyt Test
- Nuclear matrix Protein 22 (NMP22) test or BladderChek Test
- Step 1: Evaluate Hematuria with history, exam and Urinalysis
- Step 2: Imaging to characterize lesion (e.g. CT Urography)
- Step 3: Consider urine cytology
- Step 4: Cystoscopy with biopsy
- Step 5: Transurethral Resection of the Bladder (TURBT, see above)
- Step 6: Management as below based on tumor type and Bladder staging
- Management
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Urothelial - Superficial Bladder Cancer (Tis, Ta, T1)
- See surveillance for recurrence below
- Small, solitary low grade mucosal diploid tumors (Ta)
- Indication: Low risk or recurrence
- Transurethral resection
- Consider concurrent single dose of intravesical Chemotherapy or BCG within 24 hours of resection
- Indicated for tumors at higher risk of progression or recurrence (see EORTC calculator below)
- Multifocal or high grade aneuploid tumors (high grade Ta, Tis or T1)
- Risk in 50% of recurrence with Muscle-invasive disease
- Transurethral resection (TURBT) initial and repeated for restaging at 2-6 weeks after initial TURBT and
- Intravesical Immunotherapy 2 hours/week for 6-8 weeks
- Bacillus Calmette Guerin (BCG) - preferred
- Mitomycin C
- Other agents that have been used: Doxorubicin (Adriamycin), Epirubicin (Ellence), Thiopeta
- Management
-
Urothelial - Invasive Bladder Cancer (T2 to T4)
- Radical cystectomy with bilateral pelvic lymphadenectomy (superior to external beam radiation) and
- Systemic Neoadjuvant Chemotherapy: Cisplatin-Based (increases 5 year survival from the 50% for surgery alone)
- Cisplatin with Methotrexate, Vinblastine, and possibly Doxorubicin OR
- Cisplatin with Gemcitabine
- Management
-
Urothelial - Metastatic Bladder Cancer
- Management
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Nonurethelial Bladder Carcinoma
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Squamous Cell Carcinoma
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Cystectomy or Radiation Therapy
- Adenocarcinoma
- Cystectomy and
- Chemotherapy
- Consider Fluorouracil-based Chemotherapy
- Avoid M-VAC (ineffective for adenocarcinoma)
- Small Cell Carcinoma
- Cystectomy or Radiation Therapy and
- Chemotherapy
- Mixed Histology
- Treat as urothelial cancer as above
- Management
-
Bladder reconstruction after cystectomy options
- Ileal conduit urinary diversion
- Continent reservoir urinary diversion
- Monitor Serum Vitamin B12 yearly (due to repurposing of ileum)
- See Cancer Survivor Care
- Low Grade Ta
- Cystoscopy at 3 months, 12 months, then annually to year 5
- High grade Ta or T1
- Cystoscopy and urine cytology every 3-6 months for 2 years
- Then, further evaluations at increasing intervals
- Intermediate risk: Annually from year 2 to 5
- High risk: Every 6 months from year 2 to 5, then annually until year 10
- CT Abdomen and Pelvis obtained baseline in first year
- Other testing to consider (per urology or oncology)
- Upper urinary tract imaging (e.g. CT Urography) every 1-2 years up to year 10
- Urinary Tumor Marker testing (urothelial cancers only)
- Other management to consider
- Maintenance with BCG Immunotherapy (esp. if used for initial instillation)
- T2 or greater (Muscle invasive disease) after radical cystectomy
- Labs periodically
- Urine cytology
- Basic chemistry panel (including Serum Creatinine)
- Imaging every 6-12 months for 2-3 years, then yearly
- Chest imaging AND
- CT or MRI Abdomen and Pelvis
- T2 or greater (Muscle invasive disease) after Bladder-preserving surgery
- Labs every 3-6 months for 2 years and then periodically
- Urine cytology
- Basic chemistry panel (including Serum Creatinine and serum Electrolytes)
- Liver Function Tests
- Imaging every 6-12 months for 2-3 years, then yearly
- Chest imaging AND
- CT or MRI Abdomen and Pelvis
- Cystoscopy with urine cytology every 3-6 months for 2 years and then periodically
- Other measures
- Consider with selected mapping biopsy at cystoscopy
- Consider Urethral wash cytology every 6-12 months
- Especially indicated if Urethral carcinoma in situ
- References
- Carek (2024) Am Fam Physician 110(1): 37-44 [PubMed]
- Clark (2013) J Natl Compr Canc Netw 11(4): 446-75 [PubMed]
- Worse outcomes for patients continuing Tobacco Abuse
- Fleshner (1999) Cancer 86:2337-45 [PubMed]
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Muscle-Invasive Bladder Cancer
- Post-Radical Cystectomy and extensive Lymph Node dissection 5 year survival: 66%
- Procedure itself has a 3 to 9% mortality in first 90 days
- Post-Bladder preservation therapy: 50-60%
- Witjes (2014) Eur Urol 65(4): 778-92 [PubMed]
- Metastatic Bladder Cancer (untreated)
- Two year survival: <5%
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Bladder calculator for risk of Bladder Cancer progression or recurrence (EORTC)
- http://www.eortc.be/tools/bladdercalculator/
- Routine screening for Bladder Cancer is not recommended
- Eliminate modifiable risk factors (esp. Tobacco exposure and chemical exposures)
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