How is bladder cancer diagnosed?

Bladder cancers are usually found when a person goes to the doctor because of signs or symptoms they are having. If bladder cancer is suspected, tests will be needed to confirm the diagnosis.

Signs and symptoms of bladder cancer

Blood in the urine

In most cases, hematuria (blood in the urine) is the first warning sign of bladder cancer. Sometimes, there is enough blood to change the color of the urine. Depending on the amount of blood, the urine may be very pale yellow-red, pink, or, less often, darker red. In other cases, the color of the urine is normal but small amounts of blood are found during a urine test (urinalysis) done because of other symptoms or as part of a general medical checkup.

Blood may be present one day and absent the next, with the urine remaining clear for weeks or months. If a person has bladder cancer, blood eventually reappears. Usually, the early stages of bladder cancer cause bleeding but little or no pain.

Blood in the urine does not mean you have bladder cancer. Much more often it is caused by other things like an infection, benign (non-cancerous) tumors, stones in the kidney or bladder, or other benign kidney diseases. But it is important to have it checked by a doctor so that the cause can be found.

Changes in bladder habits or irritative symptoms

Bladder cancer can sometimes cause changes in urination, such as:

• Frequency: having to urinate more often than usual
• Dysuria: feeling pain or burning during urination
• Urgency: feeling as if you need to go right away, even when the bladder is not full

These symptoms are also more likely to be caused by a benign condition such as infection, benign tumors, bladder stones, an overactive bladder, or an enlarged prostate (in men). Still, it is important to have them checked by a doctor so that the cause can be found and treated, if needed.

Bladder cancers that have grown large enough may cause additional symptoms, such as lower back pain or being unable to urinate.

If there is a reason to suspect you might have bladder cancer, the doctor will use one or more methods to find out if it is cancer or something else. If it is cancer, further tests will be done to help determine the extent (stage) of the disease.

Medical history and physical exam

The first step is for your doctor to take a complete medical history to check for risk factors and to learn more about your symptoms. A physical exam provides other information about signs of bladder cancer and other health problems. The doctor might examine the rectum and vagina (in women) to help determine the size of a bladder tumor and to see if and how far it has spread.

If the results of the exam are abnormal, your doctor will probably refer you to a urologist (a doctor specializing in diseases of the urinary system and male reproductive system) for further tests and treatment.

Cystoscopy

If bladder cancer is suspected, doctors will recommend a cystoscopy. For this exam, a urologist places a cystoscope – a slender tube with a light and a lens or a small video camera on the end – through the opening of the urethra and advances it into the bladder. Sterile salt water is then injected through the scope to expand the bladder and allow the doctor to look at the bladder lining.

Cystoscopy can be done in a doctor’s office or in the operating room. Usually the first cystoscopy will be done in the doctor’s office using a small, flexible fiber-optic device. Some sort of local anesthesia may be used to numb the urethra and bladder for the procedure. If a general or spinal anesthesia is used, the procedure is done in the operating room.

If an abnormal area or a growth is seen, it will be biopsied. A thin instrument is threaded through the cystoscope to remove a small piece of tissue, which is then sent to a lab to be looked at under the microscope. Salt water washings of the inside the bladder may also be collected to look for cancer cells. (Read further for more about biopsies.)

Fluorescence cystoscopy may be done along with routine cystoscopy. For this exam, drugs called porphyrins are put into the bladder during cystoscopy. They are taken up by cancer cells. When the doctor then shines a blue light through the cystoscope, any cells containing the porphyrins will glow (fluoresce). This can help the doctor see areas with cancer cells that might have been missed by the white light normally used.

Lab tests

Urine cytology

For this test, a sample of urine is looked at under a microscope to see if it contains any cancer or pre-cancer cells. Cytology is also done on any bladder washings taken when the cystoscopy was done. Cytology can help find some cancers, but this test is not perfect. Not finding cancer on this test doesn’t always mean you are cancer free.

Urine culture

If you are having urinary symptoms, this test may be done to see if an infection (rather than cancer) is the cause. Infections and bladder cancers can cause similar symptoms. For a urine culture, a sample of urine is put into a dish in the lab to allow any bacteria that are present to grow. Because it can take time for the bacteria to grow, it may take a few days to get the results of this test.

Urine tumor marker tests

A number of different urine tests look for specific substances released by bladder cancer cells. These tests may be used along with urine cytology to help determine if a person has bladder cancer. They include the tests for NMP22 and BTA, the Immunocyt test, and the UroVysion test (discussed in the section, “Can bladder cancer be found early?”).

Some doctors find these urine tests useful in looking for bladder cancers, but they may not help in all cases. Most doctors feel that cystoscopy is still the best way to find bladder cancer. Some of these tests may be more helpful when looking for possible recurrence of bladder cancer in someone who has already had it, rather than finding it in the first place.

Biopsy

A biopsy is the removal of a sample of tissue to see if it is cancer. The tissue that is removed is sent to the lab, where it is looked at by a pathologist, a doctor who specializes in diagnosing diseases by examining tissues with a microscope. If bladder cancer is suspected, a biopsy is needed to confirm the diagnosis.

Bladder biopsies

Bladder biopsy samples are most often obtained during cystoscopy. A biopsy can show whether cancer is present and what type of bladder cancer it is. If bladder cancer is found, two important features are its invasiveness and grade.

Invasiveness: The biopsy can show how deeply the cancer has invaded (grown into) the bladder wall, which is very important in deciding treatment. If the cancer stays in the inner layer of cells without growing into the deeper layers, it is called non-invasive. If the cancer grows into the deeper layers of the bladder, it is called invasive. Invasive cancers are more likely to spread and are harder to treat.

You may also see a bladder cancer described as superficial or non-muscle invasive. These terms include both non-invasive tumors as well as any invasive tumors that have not grown into the main muscle layer of the bladder.

Grade: Bladder cancers are also assigned a grade, based on how they look under the microscope.

• Low-grade cancers look more like normal bladder tissue. They are also called well-differentiated cancers. These cancers usually have a good prognosis (outlook).
• High-grade cancers look less like normal tissue. These cancers may also be called poorly differentiated or undifferentiated. High-grade cancers are more likely to grow into the bladder wall and to spread outside the bladder. These cancers can be harder to treat.

People with bladder cancer may develop more cancers in other areas of the bladder or in the urinary system. For this reason, the doctor may take tissue samples from several different areas of the bladder lining.

Biopsies to look for cancer spread

If imaging tests (see the next section) suggest the cancer may have spread outside of the bladder, a biopsy is the only way to be sure. In some cases, biopsy samples of suspicious areas are obtained during the surgery to remove the bladder cancer.

Another way to get a biopsy sample is to use a thin, hollow needle to take a small piece of tissue from the abnormal area. This is known as a needle biopsy, and it can allow the doctor to take samples without an operation. Needle biopsies are sometimes done using a CT scan or ultrasound to help guide the biopsy needle into the abnormal area.

Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. If you have bladder cancer, your doctor may order some of these tests to see if the cancer has spread to tissues near the bladder, nearby lymph nodes, or to distant organs. If an imaging test shows enlarged lymph nodes or other possible signs of cancer spread, some type of biopsy will be needed to confirm the findings.

Intravenous pyelogram

An intravenous pyelogram (IVP), also called an intravenous urogram (IVU), is an x-ray of the urinary system taken after injecting a special dye into a vein. This dye is removed from the bloodstream by the kidneys and then passes into the ureters and bladder. The dye outlines these organs on x-rays and helps find urinary tract tumors. Some people may have allergic reactions to the dye, so it’s important to tell your doctor if you have any allergies or have ever had any reactions to x-ray dyes.

Retrograde pyelogram

For this test, a catheter (thin tube) is placed through the urethra and up into the bladder or into a ureter. Then a dye is injected through the catheter to make the lining of the bladder, ureters, and kidneys easier to see on x-rays.

This test isn’t used as often as IVP, but it may be done (along with ultrasound of the kidneys) to look for tumors in the urinary tract in people who can’t have an IVP because they are allergic to x-ray dyes.

Computed tomography (CT) scan

The CT scan is an x-ray test that produces detailed cross-sectional images of your body. Instead of taking one picture, like a standard x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body.

A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken. Spiral CT (also known as helical CT), which is now used in many medical centers, uses a faster machine that reduces the dose of radiation and creates more detailed pictures.

Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures such as blood vessels in your body.

The injection can cause some flushing (redness and warm feeling). A few people are allergic to the dye and get hives or, rarely, have more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have ever had a reaction to any contrast material used for x-rays.

A CT scan of the kidney, ureters, and bladder is known as a CT urogram. It can provide detailed information about the size, shape, and position of any tumors in the urinary tract. In some cases it may be used instead of an IVP to look at the upper part of the urinary system. It can also help find enlarged lymph nodes that might contain cancer, as well as providing information about other organs in the abdomen and pelvis.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle precisely into a suspected tumor. This is not used to biopsy tumors within the bladder, but is most often used to take tissue samples from areas where the cancer may have spread. For this procedure, the patient remains on the CT scanning table while the doctor advances a biopsy needle through the skin and toward the tumor. CT scans are repeated until the needle is within the mass. A fine needle biopsy sample or a larger core needle biopsy sample is then removed to be looked at under a microscope.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into very detailed images of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to see details more clearly

MRI scans may be a little more uncomfortable than CT scans. They often take up to an hour. You may be placed inside a narrow tube, which is confining and can upset people with a fear of enclosed spaces. Newer, more open MRI machines can sometimes be used instead. The MRI machine also makes buzzing and clicking noises that you may find disturbing. Some places will provide earplugs to help block these noises out.

MRI images are particularly useful in finding signs that the cancer 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.

Ultrasound

Ultrasound (ultrasonography) uses sound waves to create pictures of internal organs. It can be useful in determining the size of a bladder cancer and whether it has spread beyond the bladder to nearby organs or tissues. It can also be used to look at the kidneys.

This is an easy test to have. It uses no radiation, which is why it is often used to look at developing fetuses. For the exam, you simply lie on a table while a transducer (which is shaped like a wand) is placed on the skin over the part of your body being looked at. Usually, the skin is first lubricated with gel. The transducer gives off sound waves and picks up the echoes as they bounce off organs in the body. The echoes are converted by a computer into a black-and-white image.

Ultrasound-guided needle biopsy: Ultrasound can also be used to guide a biopsy needle into a suspected area of cancer spread in the abdomen or pelvis.

Chest x-ray

A chest x-ray may be done to look for spread of bladder cancer to the lungs. This test is not needed if a CT scan of the chest has been done.

Bone scan

A bone scan can help look for cancer that has spread to bones. Doctors don’t usually order this test unless you have symptoms such as bone pain, or if blood tests show the cancer might have spread to your bones.

For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV). The substance settles in areas of damaged bone throughout the entire skeleton over the course of a couple of hours. You then lie on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of the skeleton. The picture is not detailed like an MRI or CT scan, but it shows possible areas of cancer spread to all of the bones in the body at once.

Areas of active bone changes appear as “hot spots” on the skeleton – that is, they attract the radioactivity. These areas may suggest the presence of cancer, but other bone diseases can also cause the same pattern. To distinguish among these conditions, other imaging tests such as plain x-rays, MRI scans, or even a bone biopsy might be needed.