Urine biomarkers for the detection of urothelial (transitional cell) carcinoma of the bladder
- Anirban P Mitra, MD, PhD
Anirban P Mitra, MD, PhD
- University of Southern California
- Keck School of Medicine & Norris Comprehensive Cancer Center
- Marc Birkhahn, MD
Marc Birkhahn, MD
- Urologie am Ring
- David F Penson, MD, MPH
David F Penson, MD, MPH
- Professor of Urologic Surgery
- Director of Vanderbilt Center for Surgical Quality and Outcomes Research
- Richard J Cote, MD, FRCPath
Richard J Cote, MD, FRCPath
- Professor and Chair
- Department of Pathology
- University of Miami Miller School of Medicine
Urine biomarkers that currently are approved or are under development are discussed in this topic. The clinical presentation and initial diagnosis of bladder cancer, the rationale and overall approach to screening high-risk populations, and the approach to surveillance in patients who have been treated for non-muscle invasive disease are discussed separately. (See "Clinical presentation, diagnosis, and staging of bladder cancer" and "Screening for bladder cancer" and "Treatment of primary non-muscle invasive urothelial bladder cancer".)
Urine biomarkers have potential applications in individuals in whom bladder cancer is suspected based upon the presence of hematuria, overactive bladder symptoms, or an unusually high risk of tumor. Urine biomarkers may also have a role in detecting recurrences in patients who have been treated for non-muscle-invasive disease. They may also be used in the evaluation of upper tract radiographic abnormalities and for monitoring patients after treatment of ureteral or renal pelvic transitional cell carcinoma.
●Initial diagnosis – The diagnosis of bladder cancer commonly is suggested by the presence of hematuria, which may be either gross or microscopic. However, hematuria is frequently seen in a wide range of benign conditions. The diagnosis of bladder cancer ultimately requires a histologic diagnosis, which usually comes from a biopsy that is obtained at cystoscopy. Cytology may provide strong evidence for the presence of malignancy, and a positive cytology should prompt further investigation. Urine biomarkers could have a significant role in determining which individuals require cystoscopy as well as determining those who might need evaluation of the upper urinary tract. (See "Malignancies of the renal pelvis and ureter" and "Etiology and evaluation of hematuria in adults" and "Clinical presentation, diagnosis, and staging of bladder cancer", section on 'Diagnostic approach'.)
●Surveillance – Patients who have been treated for non-muscle-invasive bladder cancer are at risk for recurrence in the bladder as well as for the development of urothelial tumors in the renal pelvis, ureter, or urethra. These patients thus require prolonged follow-up. (See "Treatment of primary non-muscle invasive urothelial bladder cancer".)
Cystoscopy is the gold standard for surveillance in patients with a history of bladder cancer. Because it does not detect all recurrences nor does it visualize the upper urinary tract, a biomarker test should accompany cystoscopy in order to minimize the risk of missing a high-grade tumor. Furthermore, cystoscopy is a minimally invasive procedure. Cystoscopy is easily performed in an office setting with flexible instrumentation. However, it can be uncomfortable and promote anxiety, which can lead to suboptimal compliance with management recommendations. (See "Treatment of primary non-muscle invasive urothelial bladder cancer".)
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- POTENTIAL APPLICATIONS
- URINE BIOMARKERS
- Bladder tumor antigen (BTA) assays
- Nuclear matrix protein 22
- Other nuclear matrix proteins
- - NMP 52
- - BLCA-4 and BLCA-1
- HA and HAase
- Fibrin degradation products
- Microsatellite analysis
- DD23 monoclonal antibody
- Lewis X antigen
- MicroRNA markers
- Automated image cytometry