Update On Urine Markers For Hematuria And Bladder Cancer
Biographies:Related Content:Read the Full Video Transcript
Ashish Kamat: Hello and welcome to UroToday’s Bladder Cancer Center of Excellence. I’m Ashish Kamat from Houston MD Anderson Cancer Center. And it’s my distinct pleasure and privilege to welcome today a friend, colleague, and an expert in the field, Dr. Yair Lotan, who is Professor of Urology at UT Southwestern Medical Center in Dallas. He’s Chief of Urologic Oncology and holds a distinguished chair in honor of Dr. Roehrborn as well.
Dr. Lotan obviously needs no introduction in the field of bladder cancer and is a true expert in all things to do with bladder cancer, but especially when it comes to urinary markers. He is in many ways, actually, my go-to person when I have a question. And it was just fitting to invite you, Yair, to present to our audience what you think is new and novel and an update in urine markers for bladder cancer. So Yair, the stage is yours.
Yair Lotan: Thank you very much for inviting me to give an update on urine markers for hematuria and bladder cancer. This is an area that I’m quite passionate about, and I will try to give some focus slides on some new studies that have come out and then some commentary about the topic.
Yair Lotan: Yes, that’s correct.
Yair Lotan: Thank you so much. Appreciate your time and thanks for inviting me.
Table Of Examples Of Tumor Markers
Tumor markers often have more than one purpose and may be associated with more than one type of cancer. This table lists examples of tumor markers found on this web site and their different uses. Click on the tumor marker to go to the test article for more details on a particular marker.
How Are Tumor Markers Used In Cancer Care
There are two main types of tumor markers: circulating tumor markers and tumor tissue markers.
Circulating tumor markers can be found in the blood, urine, stool, or other bodily fluids of some patients with cancer. Circulating tumor markers are used to:
- determine the stage of cancer
- detect cancer that remains after treatment or that has returned after treatment
- assess how well a treatment is working
- monitor whether the treatment has stopped working
Although an elevated level of a circulating tumor marker may suggest the presence of cancer and can sometimes help to diagnose cancer, this alone is not enough to diagnose cancer. For example, noncancerous conditions can sometimes cause the levels of certain tumor markers to increase. In addition, not everyone with a particular type of cancer will have a higher level of a tumor marker associated with that cancer. Therefore, measurements of circulating tumor markers are usually combined with the results of other tests, such as biopsies or imaging, to diagnose cancer.
Tumor markers may also be measured periodically during cancer therapy. Such serial measurements, which show how the level of a marker is changing over time, are usually more meaningful than a single measurement. For example, a decrease in the level of a circulating tumor marker may indicate that the cancer is responding to treatment, whereas an increasing or unchanged level may indicate that the cancer is not responding.
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Diagnosis Of Bladder Cancer
Diagnosis is the process of finding out the cause of a health problem. Diagnosing bladder cancer usually begins with a visit to your family doctor. Your doctor will ask you about any symptoms you have and may do a physical exam. Based on this information, your doctor may refer you to a specialist or order tests to check for bladder cancer or other health problems.
The process of diagnosis may seem long and frustrating. Its normal to worry, but try to remember that other health conditions can cause similar symptoms as bladder cancer. Its important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of bladder cancer.
The following tests are usually used to rule out or diagnose bladder cancer. Many of the same tests used to diagnose cancer are used to find out how far the cancer has spread . Your doctor may also order other tests to check your general health and to help plan your treatment.
Summary Of Current Tests
In studies that have compared current tests in the same cohort, there is a trend that shows more robust performance of the cell-based tests . Because these tests are focused on specific cells in the sample, they are less impacted by confounders such as urinary milieu , or by conditions caused by infection, or by instrument-induced damage associated with sampling . Of the cell-based assays, cytology remains the test with the best specificity, but UroVysion improves upon sensitivity rates . Combining the tests described above does show some improvement over single tests . For example, in a study of over 2,000 cases , the PPVs of the four individual testscytology, UroVysion, ImmunoCyt, and NMP22were improved upon when they were used in almost any combination, with the combination including all four tests performing the best . However, although combining tests improves accuracy, proprietary issues mean that this currently requires multiple, distinct tests to be performed, which is not technically or economically feasible.
Another way to combine single tests into more accurate evaluations is to include the test result in a nomogram that can predict the presence of BCa , but it is clear that the derivation of multiplex molecular assays will be an important step towards overall accuracy rates that reach those of cystoscopy and cytology.
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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 312 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.
Cxbladders 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.
Meaning Of Carcinoembryonic Antigen
CEA is a protein produced by normal cells that is overexpressed in some cancers known as adenocarcinomas. CEA may be found in blood, urine, stool and other body fluids, as well as in the tumor itself. It is more likely to be produced by well-differentiated tumors than with poorly differentiated tumors.
The name “carcinoembryonic” refers to common sources of the protein, with “carcino” representing the tumors discussed and “embryonic” referring to the fact that high levels are present in the fetus during development.
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Can A Tumor Marker Be Used To Screen For Cancer
Ideally, markers could be used as a screening test for the general public. The goal of a screening test is to find cancer early, when it is the most treatable and before it has had a chance to grow and spread. So far, the only tumor marker to gain some approval as a screening tool is the Prostate Specific Antigen for prostate cancer, though this has concerns as well.
The main worry with tumor markers is that they are not specific enough they have too many false-positives. This means that the level is high when cancer is not present. This leads to costly tests that are not needed and causes the patient to be worried. The other concern is that the marker level is not high in early enough stages of the cancer, so the cancer cannot be found any earlier than when symptoms start to appear. Keep in mind that some substances used as tumor markers are normally made in the body, and a “normal” level is not always zero.
Blood Test For Bladder Cancer
Get information on having blood tests. A blood test can help measure how well your kidneys are working.
Blood tests can:
- check your general health, including how well your liver and kidneys are working
- check numbers of blood cells
- help diagnose cancer and other conditions
Your blood sample gets sent to the laboratory. Specialist technicians and doctors look at your sample under a microscope.
They can see the different types of cells and can count the different blood cells. They can also test for different kinds of chemicals and proteins in the blood.
Urine Cytology Tests After A Cystoscopy
Urine cytology tests can also be used after a procedure called cystoscopy, in which a sterile liquid is injected into the bladder to allow the bladder to expand so it can be adequately examined. When the liquid is removed from the bladder it may be analyzed with cytology testing to check for the presence of cancer or pre-cancer cells.
Bladder Cancer Diagnosis And Surveillance
Cystoscopy is a diagnostic procedure to examine directly the bladder and is considered the current gold standard for diagnosis and surveillance . This type of examination allows for a possible biopsy that can provide important information about tumors regarding the different developmental stages . It has the disadvantage of expense and is rather invasive. Nevertheless, bladder cancer has a very high cost per patient because NMIBCs have a low progression rate, but are characterized by a high recurrence rate . For this reason, patients need frequent and expensive surveillance protocols . Despite a correct treatment, some patients may develop muscle-invasive disease that has a high malignant potential and is associated with considerable progression and cancer death rates.
A chemical dipstick for hematuria offers another diagnostic test. Unfortunately, hematuria from bladder cancer may be intermittent, and it occurs also in people who do not have bladder cancer. Furthermore, the detection of the disease may be uncertain and may require repetitive screening . Intravenous urography is a diagnostic test in patients with hematuria. It is very specific for upper tract surveillance and diagnosis while the early detection of small urothelial tumors may be particularly difficult to visualize.
Computed tomography scanning is useful to identify lesions within the ureter, renal pelvis, and renal parenchyma, but is not specific.
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Role Of Urine Markers
Several reviews have been performed to assess the myriad urine markers proposed for bladder cancer surveillance. They note that none of the markers has been proven sensitive and specific enough to replace cystoscopy. While commercially available urinary markers are promising, the clinical evidence is insufficient to warrant the substitution of the cystoscopic follow-up scheme with any of the currently available urine marker tests. If FISH and NMP-22 are considered to have some utility when used to complement or replace cytology, a dilemma arises when their results conflict with each other. Of particular interest is how to treat a patient with positive cytology and/or FISH findings when cystoscopy findings are negative.
How Are Tumor Markers Used
Tumor markers may be used for a variety of purposes. However, they are not typically used alone. Depending on the type of cancer, they may be used in conjunction with a tissue biopsy or a bone marrow or blood smear examination, for example, and/or with other tumor markers. They are not definitive but provide additional information that can be used to help:
Examples of tumor markers that are used in each of these ways are provided in the table below.
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Transurethral Resection Of Bladder Tumor
If an abnormal area is seen during a cystoscopy, it needs to be biopsied to see if it’s cancer. A biopsy is when tiny pieces of the abnormal-looking tissue are taken out and tested for cancer cells. If bladder cancer is suspected, a biopsy is needed to be sure of the diagnosis.
The procedure used to biopsy an abnormal area is a transurethral resection of bladder tumor , also known as just a transurethral resection . During this procedure, the doctor removes the tumor and some of the bladder muscle around the tumor. The removed samples are then sent to a lab to look for cancer. If cancer is found, testing can also show if it has invaded the muscle layer of the bladder wall. For more on how this procedure is done, see Bladder Cancer Surgery.
Bladder cancer can sometimes start in more than one area of the bladder . Because of this, the doctor may take samples from many different parts of the bladder, especially if cancer is strongly suspected but no tumor can be seen. Salt water washings of the inside the bladder may also be collected and tested for cancer cells.
Urine Culture Testing To Check For Utis
Urine culture testing can be used to check for urinary tract infections.1 The symptoms of bladder cancers and urinary tract infections can be quite similar, so it is important for healthcare providers check for both infection and cancer if either could be the cause. To carry out this test, the urine sample is left in a dish in the laboratory for several days, which allows any bacteria that may be contained in the urine to grow.
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Magnetic Resonance Imaging Scan
Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays.
MRI images are very useful in showing cancer that has spread outside of the bladder into nearby tissues or lymph nodes. A special MRI of the kidneys, ureters, and bladder, known as an MRI urogram, can be used instead of an IVP to look at the upper part of the urinary system.
Why Did We Fail In The Past
Although noninvasive tests are labelled to diagnose bladder cancer, it remains unclear how they can effectively be integrated into clinical decision-making, particularly when making an initial diagnosis because the presenting signs and symptoms may be caused by a number of different diseases and conditions. This situation is different from that in prostate cancer screening where the diagnosis is usually being sought in asymptomatic individuals who may themselves request a screening test.
It seems obvious that new tests for the initial diagnosis of bladder cancer should be investigated in patients with symptoms and/or signs associated with this disease. This will pertain largely to patients who have gross hematuria, those who may have irritative voiding symptoms without urinary tract infection, and those found on routine urinalysis to have microscopic hematuria. However, an investigation of the literature shows that this approach is often neglected. In contrast, the vast majority of studies are case-control trials comparing artificially composed study cohorts, in which the prevalence of the disease frequently exceeds 50%. High disease prevalence is usually not seen in urological practice and such an evaluation is likely to result in an optimistic assessment of the positive predictive value .
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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
- 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
Urine Cytology Tests To Detect Cancer Cells
In a urine cytology test, a sample of the patients urine is analyzed under a microscope.1,2 This test can reveal the presence of cancer cells or cells that are pre-cancerous, meaning that they are more likely to become cancer cells later. However, this test is not enough to provide a definite diagnosis on its ownit is possible for cancer cells to be present in the bladder even if no cancer cells are detected in the urine sample.
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Can Molecular Markers Support Follow
There is clear evidence that modern molecular markers outperform urine cytology concerning sensitivity in the diagnosis of patients with noninvasive low-grade tumors. In addition, due to the low risk of tumor progression, marker-guided surveillance could significantly reduce the number of control cystoscopies without placing patients at significant risk. However, to date only one prospective trial using a marker-guided surveillance protocol has been performed . Information from this study, however, is still preliminary and does not yet permit recommendation of this procedure for clinical routine use.
Question: can molecular markers support follow-up of patients with superficial low-risk bladder cancer?
Statement: Marker-guided follow-up of patients with non-muscle-invasive low-risk tumors appears feasible. However, studies proving the efficacy of this concept and demonstrating an added value for patients or the health system are lacking.
Recommendation: Marker-guided follow-up of patients with superficial low-grade bladder cancer appears attractive however, based upon current levels of evidence this procedure cannot be recommended at present.
LoE: 1b grade: B agreement: 92%.