Bladder cancer is the 4th most common cancer in men and 8th most common cancer in women.
Epidemiology
- Incidence
- >65,000 cases yearly
- Age
- Approximately 80% are >60 years old
- Gender
- Male:female - 3-4:1
- Ethnic
- Caucasians twice as affected as Blacks
Risk Factors
- Tobacco use (raises relative risk of bladder cancer to 4)
- Occupational exposure (rubber, leather, dye and organic solvents)
- Consumption of large amounts of phenacetin for >10 years
- History of external beam irradiation (cervical or rectal cancer)
- Previous history of bladder cancer
Pathophysiology
- 90-95% are transitional cell
- Majority are superficial tumors (non-invasive)
Clinical Presentation
- Gross, painless hematuria
- 90% of cases
- Other symptoms include dysuria, frequency and flank pain
- Bone pain suggests metastatic disease
Diagnosis
- Urinalysis to confirm hematuria
- Intravenous pyelography to assess the genitourinary tract
- Noninvasive urinary antigen tests
- Not sensitive enough to use in diagnosis or as stand alone post-treatment monitoring
- Most validated tests
- Urovysion™ FISH, NMP22®, BTA stat®
- Other promising tests include:
- Cytokeratins
- Telomerase
- Microsatellite instability
- Immunocyte
- Survivin
- BCLA-4
- Soluble fas ligand
- Definitive diagnosis
- Requires invasive cystoscopic examination
Disease Monitoring
- Requires long-term monitoring and surveillance
- Main method for surveillance is cystoscopy and voided urine cytology
- Recurrence rate approximates 60%
- 42% risk of tumor progression (stage and grade) over 10 years
- Higher risk with higher pathologic stage and histologic grade
| Tests |  |
| Test name: Cytology, Urologic |
| ARUP #: 8209704 |
| Methodology: Routine Cytopathologic Evaluation |
| Use: Diagnose urothelial carcinoma in patients with signs and/or symptoms of bladder cancer (e.g., hematuria, irritative voiding symptoms) Monitor noninvasively for urothelial carcinoma in conjunction with cystoscopy in patients previously diagnosed with bladder cancer to identify residual or recurring bladder cancer |
| Limitations: Voided urine cytology (VUC) or the examination of urinary sediment for cancer cells can provide suboptimal results because of a low sensitivity for early stage and low grade bladder cancer |
| Follow-up: |
| Test name: UroVysion™ FISH |
| ARUP #: 8100600 |
| Methodology: Fluorescence in situ Hybridization/Automated Image Analysis or Manual Screening |
| Use: Monitor noninvasively for urothelial carcinoma in conjunction with cystoscopy in patients with previously diagnosed bladder cancer to identify residual or recurring urothelial carcinoma Use in conjunction with and not in lieu of current standard diagnostic procedures as an aid for initial diagnosis of bladder carcinoma in patients with hematuria Detect aneuploidy for chromosomes 3, 7, 17 and loss (deletion) of the 9p21 locus in urine specimens |
| Limitations: If test result is negative but symptoms of recurrent urothelial carcinoma still exists, additional clinical studies to exclude recurrent urothelial carcinoma should be pursued, when clinically indicated Although the Vysis® UroVysion™ Kit was designed to detect genetic abnormality associated with most urothelial cancers, some urothelial cancers will exist for which genetic changes cannot be detected by the UroVysion™ Test If test result is positive in the absence of clinical documentation of recurrence of urothelial carcinoma within the bladder, the possibility of urothelial carcinoma or other urologic malignancy from another site (including ureter, kidney, urethra and prostate) is possible; recommend further clinical evaluation to exclude these possibilities as a source of the abnormal cells |
| Follow-up: |
| Test name: Bladder Tumor Associated Antigen |
| ARUP #: 8100500 |
| Methodology: Qualitative Immunoassay |
| Use: Monitor noninvasively for urothelial carcinoma in conjunction with cystoscopy in patients with previously diagnosed bladder cancer to identify residual or recurring bladder cancer Detect bladder tumor associated antigen (hCFHrf) using qualitative immunoassay from urine |
| Limitations: Results of test should not be interpreted as absolute evidence for the presence or absence of bladder cancer False-positive test results can occur for any disease that would cause endogenous hCFH to leak into the bladder (renal stones, nephritis, renal cancer, urinary tract infections, cystitis, or recent trauma to the bladder or urinary tract) The BTA stat® Test is not approved as a screening test for bladder cancer |
| Follow-up: |
| Test name: NMP22® |
| ARUP #: 0080281 |
| Methodology: Enzyme Immunoassay |
| Use: Identify urothelial carcinoma in conjunction with cystoscopy in patients previously diagnosed with bladder cancer Use in conjunction with and not in lieu of current standard diagnostic procedures, managing patients with transitional cell carcinoma (TCC) of the bladder, after surgical treatment to identify those patients with occult or rapidly recurring TCC Determine how aggressively patients should be monitored cystoscopically after surgical treatment. |
| Limitations: Values obtained with different assay methods should not be used interchangeably. ARUP uses the Matritech NMP22® Test Kit which is an enzyme immunoassay (EIA) method An elevated result should not be interpreted as evidence of malignant disease in the urinary tract without confirmation using other diagnostic procedures False elevations may occur in: - Patients with benign urinary conditions immediately after extreme exercise in otherwise normal patients Does not replace cystoscopic follow-up for tumor recurrence The NMP22® test is not approved as a screening test for bladder cancer |
| Follow-up: |
| Test name: Immunohistochemistry Stain Offering |
| ARUP #: arup005 |
| Methodology: Immunohistochemistry |
| Use: For fixed tissue samples, consultative services as well as immunohistochemical staining for E-cadherin are available |
| Comparison of UroVysion™ FISH vs. Cystoscopy/Histology for Detection of Bladder Cancer Recurrence by Stage and Grade | |
| Agreement of (+) Results (%) | |
| Stage | |
| Ta, Grade 1 | 36/48 (75.0%) |
| Ta, Grade 2-3 | 11/20 (55.0)% |
| T1 | 10/12 (83.3%) |
| T2 | 3/3 (100%) |
| Tis | 7/7 (100%) |
| Grade | |
| All | 36/49 (73.5%) |
| 1 | 12/22 (54.5%) |
| 2 | 7/9 (77.8%) |
| 3 | 17/18 (94.4%) |
| Sensitivity and Specificity of BTA stat® and Standard Cytology Sensitivity and specificity were determined on the same samples used in the comparison study between UroVysion™ FISH and Cystoscopy/Histology | |||||
| TaG1 | TaG2,3 | T1 | T2 | Tis | |
| Cytology Sensitivity | 20% | 30% | 67% | 33% | 33% |
| BTA stat® Sensitivity | 30% | 83% | 83% | 67% | 43% |
| Grade 1 | Grade 2 | Grade 3 | |||
| Cytology Specificity | 18% | 44% | 41% | ||
| BTA stat® Specificity | 18% | 44% | 41% | ||
Guidelines
General References
Comprehensive Review: January 2008
Last Update: January 2008
