Detecting Bladder Cancer with a Urine Test
Urine is made up of several components including water and waste materials filtered from the blood by the kidneys, as well as small numbers of cells such as epithelial cells shed from the lining of the urinary tract and possibly red and white blood cells. The type and quantity of the different components and cells contained in urine can provide important information regarding an individual’s health, which can help in the diagnosis of diseases such as bladder cancer.
What can be detected in a urine test?
Urine testing can assist in diagnosing many different disorders including kidney disease, diabetes, liver disorders, urinary tract infections (UTIs), and bladder cancer.
Urine samples are routinely examined for physical properties (e.g., color, clarity, odor, density), chemical composition (e.g., pH, protein, glucose; commonly determined by a simple dipstick test) and microscopic appearance (e.g., the presence of cells, crystals, or bacteria). To detect bacteria, urine culture may also be performed, as described later.
Abnormal findings in a urine test can be characteristic of certain disease processes. For instance, persistently elevated protein in urine is a common early sign of chronic kidney disease, high levels of glucose may indicate diabetes, the detection of bacteria is often associated with a UTI, and the presence of red blood cells or abnormal cells may indicate bladder cancer.
In recent years there has been increasing use of molecular diagnostic tests to detect specific proteins or nucleic acids (RNA or DNA) in urine to diagnose diseases such as UTIs, prostatitis, or bladder cancer. Cxbladder, for example, measures the urine concentration of messenger RNA (mRNA) expressed by five biomarker genes to determine the presence or absence of bladder cancer.
How are samples collected?
Requirements for urine sampling vary depending on the test/s being performed. Often the timing of collection is random, as dictated by the logistics of a doctor consult or access to a laboratory service. However, depending on the purpose of the test, certain urine voids of the day (e.g., the first or second void) may be preferred. Collection of urine from all voids over a defined time period (usually over 8 or 24 hours) or sample collection at specific times after eating may also be necessary.
Urine samples are usually obtained by spontaneous voiding, using the clean-catch, midstream urine collection method. This involves voiding the first portion of urine into the toilet, collecting the midstream portion into a clean container, then voiding the remaining portion into the toilet. This method greatly reduces the risk of contaminants entering the sample. Less commonly, an invasive method of urine collection, such as placement of a urinary catheter, may be required.
Learn about Cxbladder's easy-to-use in-home sampling system
Benefits of urine testing
Urine testing has several advantages, including:
- Typically non-invasive and painless
- Ease of sampling, coupled with being quick and convenient compared with other tests and procedures (e.g., Cxbladder allows for in-home sample collection)
- Results can be obtained quickly
- Costs are often lower than those associated with other types of diagnostic tests and procedures
- Provides relevant, reliable information regarding patient health status (to maximize accuracy it is important that urine samples are collected, stored, and transported correctly)
Can a urine test detect bladder cancer?
Several types of urine test have an important role in the overall process of diagnosing bladder cancer. Among these tests, urine cytology and urine tumor marker tests are used to detect the presence or absence of bladder cancer. Urine cytology has been used to assist bladder cancer diagnosis for over 75 years and has well-established strengths and limitations which are discussed in more detail below. Molecular tumor marker tests such as Cxbladder have been more recently developed, and provide high diagnostic accuracy in both detection and rule-out.
Notably, no single test is best able to detect bladder cancer, and usually different types of tests (i.e., urine tests, cystoscopy, and imaging techniques) are used in combination. For example, the Cxbladder genomic urine test in combination with ultrasound or computed tomography (CT) imaging has been shown to identify the presence or absence of bladder cancer with high accuracy in patients with hematuria. The specific diagnostic tests selected depend on several factors, including a patient’s symptoms and their risk for bladder cancer.
Urine-based tests used in the diagnosis of bladder cancer
Urinalysis examines several physical, chemical, and microscopic features of urine samples. The most common early sign of bladder cancer is the presence of blood in the urine (‘hematuria’), which may occur in amounts visible to the naked eye (‘gross hematuria’) or in smaller amounts detectable only by microscopy or other laboratory tests (‘microhematuria’). Urine dipstick testing is a quick, inexpensive method often used to initially identify microhematuria, with further microscopic evaluation necessary to confirm that red blood cells are present in abnormal quantities. In individuals who do not have other urinary symptoms, microhematuria is confirmed by the presence of three or more red blood cells per high powered microscopic field.
- Urine Culture
As hematuria and other early signs of bladder cancer such as urinary symptoms have several possible causes (e.g., kidney stones, bladder infections or UTIs, prostate enlargement), the more common causes are usually investigated first. Urine culture is routinely carried out to detect the presence of infection; in this laboratory test, samples of urine are introduced onto nutrient gels that enable any bacteria present to grow and be identified.
Notably, although urinalysis and urine culture are relevant steps in the process of bladder cancer diagnosis, these tests cannot determine the presence (or absence) of bladder cancer.
- Urine Cytology
Urine cytology refers to the microscopic examination of cells from urine samples. This procedure can potentially detect cancerous cells in the urine of individuals with bladder cancer. The use of urine cytology to diagnose bladder cancer is based on the principle that rapidly multiplying cancer cells will be shed into the urine. However, because the rate of shedding depends on the properties of each tumor (e.g., lower grade tumors may shed fewer cells than higher grade tumors) and may not be consistent over time, the ability of urinary cytology to detect bladder cancer varies among tumor types and is relatively low overall, often yielding equivocal or atypical results. Recent analyses indicate that urine cytology detects only around 50% of high-grade tumors and 10% of low-grade tumors, with an overall sensitivity for bladder cancer detection of approximately 40%.1 This means that overall, approximately 60% of all bladder cancers will be missed by urine cytology. While a positive urine cytology result does reliably indicate the presence of bladder cancer (as false positive cytology results are rare), a negative result does not confirm its absence.
Urine cytology is most commonly used in combination with cystoscopy for the initial detection and characterization of bladder cancer, and in ongoing monitoring for recurrence.
- Urine Tumor Marker Tests
A urine tumor marker is simply defined as a biological molecule found in urine that indicates the presence of bladder cancer. If a patient has bladder cancer, cells from the tumor will release biomarkers into the urine. A broad range of urine tumor markers for bladder cancer have been identified, including numerous proteins and metabolites, as well as genetic materials such as DNA and RNA. Several of these markers have been used to develop diagnostic tests that are now available commercially. Cxbladder is a genomic urine test as it analyses messenger RNA (mRNA) to measure five biomarker genes.
Urine tumor marker tests are often used in combination with other urine-based tests, imaging and/or cystoscopy to detect bladder cancer or monitor for its recurrence. Advantages of this approach include improved detection accuracy (that is, less chance bladder cancer will be missed), alongside the potential to make the investigation of hematuria less intensive or to reduce the need for, and frequency of, invasive cystoscopy procedures (particularly for patients deemed low risk).
Cxbladder is a genomic urine test for bladder cancer that improves overall detection accuracy
Cxbladder is a non-invasive and easy-to-use genomic urine test that quickly and accurately detects or rules out bladder cancer. The test combines clinical risk factor markers with genetic information, measuring five biomarker genes to detect the presence or absence of bladder cancer.
When should you use Cxbladder?
- When you've seen blood in your urine
- If tests reveal you have blood in your urine
- When you have had bladder cancer and are being monitored for recurrence
Cxbladder provides greater certainty, resolving diagnostic ambiguity and improving overall detection accuracy. The use of Cxbladder can also reduce the need for further invasive procedures and testing.
Bladder cancer has a high risk of recurrence so patients who have been treated have unique monitoring needs to protect against the threat of the disease returning. Besides monitoring for signs and symptoms of bladder cancer, a cystoscopy to examine the inside of the bladder and urethra is recommended every 3–12 months for several years after completing bladder cancer treatment, depending on the risk of recurrence. For many patients, the frequency of cystoscopy required can be reduced with the use of Cxbladder, a non-invasive surveillance alternative.
Cxbladder’s proven accuracy makes it a reliable choice. With performance proven in over 10 peer-reviewed studies, Cxbladder is trusted by over 1,800 urologists in over 40,000 patients. The test is covered by Medicare and comes with the option of in-home sampling.
Learn more about Cxbladder Contact us for more information
- Freifeld Y, Lotan Y. Effect of blue-light cystoscopy on contemporary performance of urine cytology. BJU Int. 2019 Aug;124:251-257.
- American Cancer Society. Tests for Bladder Cancer. Accessed April 21, 2021.
- American Society of Clinical Oncology. Bladder Cancer: Symptoms and Signs. Accessed April 21, 2021.
- BPAC NZ. Interpreting urine dipstick tests in adults: a reference guide for primary care. Best Tests; June 2013.
- Chaudhuri AA, Pellini B, Pejovic N, et al. Emerging Roles of Urine-Based Tumor DNA Analysis in Bladder Cancer Management. JCO Precis Oncol. 2020 15;4:PO.20.00060.
- Davidson PJ, McGeoch G, Shand B. Assessment of a clinical pathway for investigation of haematuria that reduces the need for cystoscopy. NZ Med J. 2020;133:71-82.
- Davis R, Jones JS, Barocas DA, et al. Diagnosis, Evaluation and Follow-up of Asymptomatic Microhematuria (AMH) in Adults (reviewed 2016). American Urological Association. Available at www.auanet.org/guidelines/archived-documents/asymptomatic-microhematuria-(amh)-guideline.
- Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6:140-146.
- Lotan Y, OʼSullivan P, Raman JD, et al. Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urol Oncol. 2017;35:531.e15-531.e22.
- National Kidney Foundation. Why are patients asked for urine samples? Accessed April 21, 2021.
- Oliveira MC, Caires HR, Oliveira MJ, et al. Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles. Cancers (Basel). 2020;12:1400.
- Queremel Milani DA, Jialal I. Urinalysis. (Updated 2020 May 30). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing. Accessed April 21, 2021.
- UpToDate. Lotan Y, Choueiri TK. Clinical presentation, diagnosis, and staging of bladder cancer. Accessed June 3, 2021.
- UptoDate. O’Leary, MP. Blood in the urine (hematuria) in adults (Beyond the Basics). Accessed April 21, 2021.
- Urotoday. Schaeffer, E. UTI – Is Traditional Culture Testing Obsolete? Published March, 2020. Accessed June 3, 2021.
Last Updated: 04 Aug 2022 10:55 am
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