Can Molecular Markers Support Screening Of Patients At Risk Of Having Or Developing Bladder Cancer
When considering bladder cancer screening, the key question to be answered is if early detection of bladder cancer may have any impact on cure rates and, subsequently, on patient survival. Over the last decades, a growing body of evidence has been accumulated suggesting that early detection and treatment of bladder cancer may indeed reduce cancer-specific mortality , thus providing arguments for this procedure. However, due to the low prevalence of bladder cancer in the general population and in people above the age of 50 , mass screening for bladder cancer, with the possibility of detecting a significant number of false positives requiring unnecessary work-up, would certainly not be cost-effective . As a consequence of these considerations, those few trials addressing screening for bladder cancer targeted high-risk populations.
Data obtained in high-risk groups undergoing urinary dipstick screening for bladder cancer suggest that the bladder tumors discovered when evaluating all patients with asymptomatic microscopic hematuria may be more amenable to curative treatment than those normally encountered, thereby reducing morbidity and mortality associated with bladder cancer in these patients . Since improved survival of screened patients was not demonstrated in a randomized fashion, but only in comparison with a cancer register, this study presents interesting information however, it cannot serve to provide a final decision on the benefit of hematuria screening.
Tests That Might Be Used To Look For Bladder Cancer
Tests for bladder cancer look for different substances and/or cancer cells in the urine.
Urinalysis: One way to test for bladder cancer is to check for blood in the urine . This can be done during a urinalysis, which is a simple test to check for blood and other substances in a sample of urine. This test is sometimes done as part of a general health check-up.
Blood in the urine is usually caused by benign problems, like infections, but it also can be the first sign of bladder cancer. Large amounts of blood in urine can be seen if the urine turns pink or red, but a urinalysis can find even small amounts.
Urinalysis can help find some bladder cancers early, but it has not been shown to be useful as a routine screening test.
Urine cytology: In this test, a microscope is used to look for cancer cells in urine. Urine cytology does find some cancers, but it’s not reliable enough to make a good screening test.
Urine tests for tumor markers: Newer tests look for certain substances in urine that might be a sign of bladder cancer. These include:
How Is Bladder Cancer Diagnosed
Arriving at a diagnosis of bladder cancer may involve one or more of these steps:
- Urine tests to detect blood, cancer cells and other signs of disease. A 24-hour urine collection can measure volume of urine output, an indicator of kidney function.
- Bladder wash during which a solution is delivered through a catheter to the bladder to loosen cells on the bladders inner lining. The solution is removed, and a sample is examined under a microscope.
- Blood tests to assess kidney and liver function
- Cystoscopy to see inside the bladder and identify any tumor
- Imaging Scans to determine if a cancer has spread
- Transurethral Resection of Bladder Tumor to obtain a biopsy, confirm a cancer diagnosis, and determine the stage and grade of a cancer
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What Are The Risk Factors For Bladder Cancer
Some factors increase the risk of bladder cancer:
- Cigarette smoking is the biggest risk factor it more than doubles the risk. Pipe and cigar smoking and exposure to second-hand smoking may also increase one’s risk.
- Prior radiation exposure is the next most common risk factor .
- Certain chemotherapy drugs also increase the risk of bladder cancer.
- Environmental exposures increase the risk of bladder cancer. People who work with chemicals, such as aromatic amines are at risk. Extensive exposure to rubber, leather, some textiles, paint, and hairdressing supplies, typically related to occupational exposure, also appears to increase the risk.
- Infection with a parasite known as Schistosoma haematobium, which is more common in developing countries and the Middle East.
- People who have frequent infections of the bladder, bladder stones, or other diseases of the urinary tract, or who have chronic need for a catheter in the bladder, may be at higher risk of squamous cell carcinoma.
- Patients with a previous bladder cancer are at increased risk to form new or recurrent bladder tumors.
Other risk factors include diets high in fried meats and animal fats, and older age. In addition, men have a three-fold higher risk than women.
Understanding Invasiveness And Grade
Two important pieces of information to know about this specific cancer are its invasiveness and grade.
Invasiveness describes how deep the cancer is in the bladder wall, which is crucial to determining treatment. If the cancer is in the inner cell layers, its noninvasive or superficial. If its grown into deeper bladder layers or spread to other organs or lymph nodes, its invasive.
Grade describes how bladder cancer cells look under a microscope. Low-grade cancers, also called well-differentiated cancers, resemble regular bladder cells. High-grade, poorly differentiated or undifferentiated cancers dont look as much like normal bladder cells, and theyre more likely to become invasive or spread to other body parts.
Invasive and high-grade cancers may be harder to treat than noninvasive and low-grade ones. They may also require a different kind of treatment.
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Biochemistry Tests For Urine Tumor Markers
- Recently, innovative tests have been designe to find substances in the urine that might indicate early detection of bladder cancer. These are as follows:
- Urovysion Bladder cancer kit-utilizes fluorescence in situ hybridization technique of urine specimens to observe chromosome abnormalities associated with cancer cells of the bladder.
- NMP22 bladderCheck-nuclear matrix protein is a normal bladder protein whose levels are unusually high during the development of bladder cancer. The test utilizes an assay technique called ELISA to detect the elevated protein levels. It is a rapid assay method which lasts only 30 minutes with 4 drops of urine.
- ImmunoCyt urine test-This is a highly sensitive and reasonably specific test used in particular, for the detection of bladder cancer. In particular cells are separated from the urine and tested for mucin and carcinoembryonic antigen , which are frequently present in cancer cells. In general, the test utilizes ELISA technique to determine the presence of these two cancer marker proteins.
- BTA-Track test-This is a quantitative ELISA test that utilizes urine sample to determine the presence of bladder tumor-associated antigen in the urine. In this case, a positive result is an indication that bladder cancer might be developing.
- Bence-Jones Protein test-This is an abnormal protein present in the urine of approximately 50% of patients suffering from multiple myeloma . ELISA technique is utilized to detect this unusual protein in a urine sample.
What Are The Treatment Options For Bladder Cancer
There are four types of treatment for patients with bladder cancer. These include:
Sometimes, combinations of these treatments will be used.
Surgery is a common treatment option for bladder cancer. The type of surgery chosen will depend on the stage of the cancer.
- Transurethral resection of the bladder is used most often for early stage disease . It is done under general or spinal anesthesia. In this procedure, a special telescope called a resectoscope is inserted through the urethra into the bladder. The tumor is then trimmed away with the resectoscope, using a wire loop, and the raw surface of the bladder is then fulgurated .
- Partial cystectomy is the removal of a section of the bladder. At times, it is used for a single tumor that invades the bladder wall in only one region of the bladder. This type of surgery retains most of the bladder. Chemotherapy or radiation therapy is often used in combination. Only a minority of patients will qualify for this bladder-sparing procedure.
- Radical cystectomy is complete removal of the bladder. It is used for more extensive cancers and those that have spread beyond the bladder .
This surgery is often done using a robot, which removes the bladder and any other surrounding organs. In men, this is the prostate and seminal vesicles. In women, the ovaries, uterus and a portion of the vagina may be removed along with the bladder.
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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 may be preferred. Collection of urine from all voids over a defined time period 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.
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Bladder Tumor Associated Antigen Assays
Two versions of the BTA test are available: BTA stat, an immunochromatographic, qualitative point-of-care assay , and BTA TRAK, an ELISA test that measures the human complement factor H -related protein in a quantitative fashion . These assays are FDA-approved for the detection and surveillance of BCa in urine samples . They are simple to perform and interpret, and the versatility of the point-of-care format enables testing at outpatient clinics. For BCa detection, urinary BTA tests have diagnostic sensitivities ranging from 29 to 91 % and specificities ranging from 56 to 86 % . While sensitivities can be better for BTA over cytology, the specificity is impacted by other non-cancerous conditions .
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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.
Urine Test May Revolutionize Bladder Cancer Detection
We were unable to process your request. Please try again later. If you continue to have this issue please contact .Maximilian Diehn
A novel urine test may detect bladder cancer earlier than available methods, according to study results published in Cancer Discovery.
Maximilian Diehn, MD, PhD, associate professor of radiation oncology at Stanford University, and colleagues developed a high-throughput sequencing-based hybrid capture method for urine tumor DNA detection.
They speculated that the approach called uCAPP-Seq would be superior to cytology for detection of early-stage bladder cancer and posttreatment residual disease.
Diehn and colleagues assessed their approach in a study of 67 healthy adults and 118 patients with early-stage bladder cancer who either had urine collected prior to treatment or during surveillance.
The method detected tumor DNA in 84% of cases when using an approach blinded to tumor mutation status and 93% of cases using a tumor mutation-informed approach. Researchers reported specificity of 96% to 100%.
During surveillance, investigators detected tumor DNA in 91% of patients who recurred, and detection preceded clinical progression in 92% of cases.
Detecting bladder cancer DNA in urine appears to be an extremely promising approach for both early detection and surveillance of bladder cancer, Diehn told HemOnc Today. Our findings suggest that this approach should also be explored for other cancers affecting the urinary tract.
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Hyaluronic Acid And Hyaluronidase
Hyaluronic acid is a nonsulfated glycosaminoglycan found in normal tissue and tissue fluids. When present in tumor tissues, it promotes metastasis and may interfere with immune surveillance. At a cutoff value of 100 ng/mL, urine HA had 92% sensitivity and 93% specificity for detecting bladder cancer.
Hyaluronidase , an endoglycosidase, degrades HA into small fragments that promote angiogenesis. Hyaluronidase secretion by bladder tumor cells correlates with invasive potential. Pham and coworkers analyzed 139 urine specimens and detected a 5- to 8-fold elevation of hyaluronidase in the urine of patients with grade 2 or 3 bladder cancer. However, its widespread applicability may be somewhat limited the accuracy of this test for detecting low-grade tumor is poor and may even be less than that of routine voided urine cytology. Further refinement in the assay technique and evaluation in larger clinical trials would help to define the clinical applicability of this marker.
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.
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Elypta Expands Trial For Liquid Biopsy Kidney Cancer Recurrence Test Plans Bladder Cancer Assay
NEW YORK Elypta, a Swedish diagnostics developer, has commenced a clinical trial of its metabolite-based liquid biopsy platform for the prognosis and potential guidance of treatment of muscle-invasive bladder cancer.
The 4-year-old firm this week also announced that it has expanded an ongoing trial of a test in development for recurrent kidney cancer. Elypta is also developing a third test for the early detection of multiple cancers, which the company believes could eventually be used for routine cancer screening.
“The bulk of our research to date has gone toward kidney cancer as our first indication,” said CEO Karl Bergman in an interview this week. “Since we started Elypta though, we knew that our platform had a wider potential to detect cancer across classes,” he said. “We were thinking of where it fit best, and bladder cancer is near the top of that list next to kidney cancer and a multicancer early detection test.”
Elypta was founded in 2017 to commercialize technology developed at Chalmers University of Technology in Gothenburg. The firm is based in Solna, just outside Stockholm, and currently employs about 15 people, Bergman said. Its core platform is capable of measuring a panel of metabolites called glycosaminoglycans, or GAGs, in blood or urine in order to detect cancer.
“This study started right when the pandemic started,” acknowledged Bergman. “COVID-19 slowed us down, but now the sites are up again.”
Multicancer early detection test
How Is Urine Collected For Cancer Cytology Tests
- Urine is usually collected at your doctors office, clinic or a lab, but if it is 24-hour urine collection, you will be shown the procedure you will need for home collection.
- In general, it is advisable to collect first-morning urine.
- Midstream urine with no contamination from germs of the vagina or penis is required for testing.
- You may be provided with sterile, clean catch kit by your doctor containing a cleansing solution, sterile wipes, and collection container.
- You wash your hands first, open the kit, clean your genital area and then begin urinating.
- After the urine has flowed about half way, you collect midstream into the container, as you continue with the urine flow in the toilet until completion.
- Careful tighten the lid on the urine container and return urine sample to your doctor.
- Your urine sample will be sent to a lab within an hour for examination.
A urine sample can also be obtained during cystoscopy procedure .
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Early Detection And Screening
Because bladder cancer causes urinary symptoms such as blood in the urine, it may be found early. However, because blood in urine is caused by a lot of conditions other than cancer, urinalysis isnt a useful screening test for the general population.
There isnt a test yet that is able to screen the general population for bladder cancer. Doctors may recommend specific tests to screen for bladder cancer based on known risk factors.
Urine Test For Cancer
Urine test for cancer utilizes midstream urine sample to detect disease in body, which includes different types of infections. In this case, urinalysis is used to check if there is blood in the urine as an indication of infection or if certain types of drugs are present. The tests analyze urine by physical, microscopical and biochemical techniques. If a cancer diagnosis is being sought, the cells are collect from the urine by centrifugation and a special microscope is utilize to examine cells and plausible cancer activity they exhibit and this is refer to as urine cytology test.
For cancer detection, if the urinalysis tests reveal abnormal cells, additional tests are carry out to obtain more information in order to confirm that there has been the development of cancer. Urinalysis tests have been use as a convenient method of identifying bladder cancer at early stages but it is not solely use as a screening test however, other techniques are use to confirm a positive urine test result.
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