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Urothelial Carcinoma

Definition

Bladder cancer occurs when cells in the bladder start to grow without control. The bladder is a hollow, balloon-shaped organ in the lower part of the abdomen that stores urine.

The bladder has a muscular wall that allows it to get larger to store urine made by the kidneys and to shrink to squeeze urine out of the body. There are two kidneys, one on each side of the backbone, above the waist. The bladder and kidneys work together to remove toxins and wastes from your body through urine:

  • Tiny tubules in the kidneys filter and clean the blood.
  • These tubules take out waste products and make urine.
  • The urine passes from each kidney through a long tube called a ureter into the bladder.
  • The bladder holds the urine until it passes through a tube called the urethra and leaves the body.

Black Americans are less likely to get bladder cancer than other racial or ethnic groups, however, they are more likely to die from this form of cancer, according to a 2017 National Institutes of Health study.

Types of Bladder Cancer

Urothelial carcinoma (also called transitional cell carcinoma) is cancer that begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs. Almost all bladder cancers are urothelial carcinomas.

Urothelial cells are also called transitional cells because they change shape. These cells are able to stretch when the bladder is full of urine and shrink when it is emptied.

Other types of bladder cancer are rare:

  • Squamous cell carcinoma is cancer that begins in squamous cells (thin, flat cells lining the inside of the bladder). This type of cancer may form after long-term irritation or infection with a tropical parasite called schistosomiasis, which is common in Africa and the Middle East but rare in the United States. When chronic irritation occurs, transitional cells that line the bladder can gradually change to squamous cells.
  • Adenocarcinoma is cancer that begins in glandular cells that are found in the lining of the bladder. Glandular cells in the bladder make mucus and other substances.
  • Small cell carcinoma of the bladder is cancer that begins in neuroendocrine cells (nerve-like cells that release hormones into the blood in response to a signal from the nervous system).

There are other ways to describe bladder cancer:

  • Non-muscle-invasive bladder cancer is cancer that has not reached the muscle wall of the bladder. Most bladder cancers are non-muscle-invasive.
  • Muscle-invasive bladder cancer is cancer that has spread through the lining of the bladder and into the muscle wall of the bladder or beyond it.

Symptoms

The symptoms of bladder cancer can vary from person to person. The most common symptom is blood in the urine, called hematuria. It’s often slightly rusty to bright red in color. You may see blood in your urine at one point, then not see it again for a while. Sometimes there are very small amounts of blood in the urine that can only be found by having a test done.

Other common symptoms of bladder cancer include

  • frequent urination
  • pain or burning during urination
  • feeling as if you need to urinate even if your bladder isn’t full
  • urinating often during the night

When the cancer has grown large or spread beyond the bladder to other parts of the body, symptoms may include

  • being unable to urinate
  • lower back pain on one side of the body
  • pain in the abdomen
  • bone pain or tenderness
  • unintended weight loss and loss of appetite
  • swelling in the feet
  • feeling tired

It’s important to check with your doctor if you have any of these symptoms. Keep in mind that urinary tract infections, kidney or bladder stones, or other problems related to the kidney could be the cause, not cancer. Your doctor will ask you when your symptoms started and how often you’re having them. They will most likely ask you to give a urine sample as a first step in diagnosing what is causing your symptoms.

Causes

Bladder cancer is caused by certain changes in how bladder cells function, especially how they grow and divide into new cells. There are many risk factors for bladder cancer, but many do not directly cause cancer. Instead, they increase the chance of DNA damage in cells that may lead to bladder cancer.

Risk Factors

Using tobacco, especially smoking cigarettes, is a major risk factor for bladder cancer. Tobacco contains harmful chemicals called carcinogens. When you use tobacco, these chemicals get absorbed into the bloodstream, are filtered by the kidneys, and then collect in the urine. This exposes your bladder to high levels of these chemicals, which can damage the DNA in the cells lining your bladder.

Other risk factors for bladder cancer include

  • having a family history of bladder cancer
  • having certain changes in the genes that are linked to bladder cancer, such as HRAS, RB1, PTEN/MMAC1, NAT2, and GSTM1
  • being exposed to paints, dyes, metals, or petroleum products in the workplace
  • past treatment with radiation therapy to the pelvis or with certain anticancer drugs, such as cyclophosphamide or ifosfamide
  • taking the Chinese herb Aristolochia fangchi
  • drinking water from a well that has high levels of arsenic
  • drinking water that has been treated with chlorine
  • having a bladder infection caused by a parasite called Schistosoma haematobium, which is common in Africa and the Middle East but rare in the United States
  • using urinary catheters for a long time

Having one or more of these risk factors does not necessarily mean you will get bladder cancer. Many people with risk factors never develop bladder cancer, while others with no known risk factors do. Talk with your doctor if you think you might be at risk of bladder cancer. Bladder cancer screening options may be available to you.

Screening

Screening is looking for cancer before a person has any symptoms. This can help find cancer at an early stage. When abnormal tissue or cancer is found early, it may be easier to treat.

Tests to screen for bladder cancer

There is no standard screening test for bladder cancer in people at average risk. When enough evidence has been collected to show that a screening test is safe, accurate, and useful for people at average risk of bladder cancer, it will become a standard test. However, certain tests may be used to screen for bladder cancer in people who have had bladder cancer in the past or who are at an increased risk of developing it.

Hematuria test

Hematuria is red blood cells in the urine. It may be caused by cancer or by other conditions. A hematuria test is used to check for blood in a sample of urine by viewing it under a microscope or using a special test strip. The test may be repeated over time.

Urine cytology

Urine cytology is a lab test in which a sample of urine is checked under a microscope for abnormal cells.

Urine tumor marker tests

Urinary tumor markers are substances found in the urine that are either made by bladder cancer cells or that the body makes in response to bladder cancer. For this test, a sample of urine is checked in the lab to detect the presence of these substances. Urine tumor marker tests may also be used to help diagnose some types of bladder cancer.

Cystoscopy

Cystoscopy is a procedure to look inside the bladder and urethra to check for abnormal areas. A cystoscope (a thin, lighted tube) is inserted through the urethra into the bladder. Tissue samples may be taken for biopsy.

Risks of bladder cancer screening

Screening tests have benefits and risks. Talk with your doctor about whether bladder cancer screening is right for you.

Potential risks of harm from bladder cancer screening include false-positive and false-negative test results:

  • False-positive test results. Screening test results may appear to be abnormal even though no cancer is present. A false-positive test result (one that shows there is cancer when there isn’t) can cause anxiety and is usually followed by more tests (such as cystoscopy or other invasive procedures), which also have risks. False-positive results often occur with hematuria testing; blood in the urine is usually caused by conditions other than cancer.
  • False-negative test results. Screening test results may appear to be normal even though bladder cancer is present. A person who receives a false-negative test result (one that shows there is no cancer when there is) may delay seeking medical care even if there are symptoms.

Diagnosis

If you have symptoms or lab test results that suggest bladder cancer, your doctor will need to find out if they’re due to cancer or another condition. Your doctor may

  • ask about your personal and family medical history to learn more about your symptoms and possible risk factors for bladder cancer
  • ask for a sample of your urine so it can be checked in the lab for blood, abnormal cells, or infection
  • do a physical exam, which for women, may include a pelvic exam, to check for signs of cancer

Depending on your symptoms, medical history, and results of your urine lab tests and physical exam, your doctor may recommend more tests to find out if you have bladder cancer, and if so, its extent (stage).

Biopsy

A biopsy is usually done during a cystoscopy procedure. Biopsy is a procedure in which a sample of cells or tissue is removed from the bladder so that a pathologist can view it under a microscope to check for signs of cancer. It may be possible to remove the entire tumor at the time of the biopsy.

Talk with your doctor to learn what to expect during and after your cystoscopy and biopsy. Some people have blood in the urine or discomfort and a burning sensation while urinating for a day or two.

To learn about the type of information that can be found in a pathologist’s report about the cells or tissue removed during a biopsy, see Pathology Reports.

Computed tomography (CT) urogram or intravenous pyelogram (IVP)

CT urogram is a test that takes a CT scan of the urinary tract using a contrast dye injected into a vein. To begin the procedure, a CT machine takes a series of detailed pictures of the kidneys. The contrast dye is then injected, and another CT scan of the kidneys, bladder, and ureters is done. About 10 minutes later, a final scan is taken as the contrast dye drains from the kidneys into the bladder. CT urogram also captures detailed pictures of nearby bones, soft tissues, and blood vessels. This allows the doctor to see how well your urinary tract is working and to check for signs of disease.

IVP is an x-ray imaging test of your urinary tract. After a contrast dye is injected into a vein, a series of x-ray pictures of the kidneys, ureters, and bladder are taken to find out if cancer is present in these organs. As the contrast dye moves through the kidneys, ureters, and bladder, more x-ray pictures are taken at specific times. This allows your doctor to see how well your urinary tract is working and to check for signs of disease.

Urine tumor marker test

Urinary tumor markers are substances found in the urine that are either made by bladder cancer cells or that the body makes in response to bladder cancer. For this test, a sample of urine is checked in the lab to detect the presence of these substances. Urine tumor marker tests may be used to help diagnose some types of bladder cancer.

Tests to stage bladder cancer

If you’re diagnosed with bladder cancer, you will be referred to a urologic oncologist. This is a doctor who specializes in diagnosing and treating cancers of the male and female urinary tract and the male reproductive organs. They will recommend tests to determine the extent of cancer. Sometimes the cancer is only in the bladder. Or, it may have spread from the bladder to other parts of the body. The process of learning the extent of cancer in the body is called staging. It is important to know the stage of the bladder cancer to plan treatment.

The following imaging tests may be used to determine the bladder cancer stage.

Computed tomography (CT) scan

A CT scan uses a computer linked to an X-ray machine to make a series of detailed X-ray pictures of areas inside the body from different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly.

Magnetic resonance imaging (MRI)

MRI uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the bladder. This procedure is also called nuclear magnetic resonance imaging. Images may be taken at three different times after the dye is injected, to get the best picture of abnormal areas in the bladder. This is called triple-phase MRI.

Chest x-ray

A chest X-ray is an X-ray of the organs and bones inside the chest. An X-ray is a type of high-energy radiation that can go through the body and onto film, making a picture of areas inside the chest.

Bone scan

A bone scan is a procedure that checks to see if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones with cancer and is detected by a scanner.

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