Urothelial carcinoma

Urothelial carcinoma is a cancer that starts in urothelial cells. These cells line much of the urinary tract, including the bladder, renal pelvis, ureters and part of the urethra.

The renal pelvis is the part of the kidney where urine collects. The ureters are tubes that carry urine from the kidneys to the bladder. Urothelial carcinoma used to be called transitional cell carcinoma.

Most urothelial carcinomas start in the bladder. In the United States and Europe, urothelial carcinoma accounts for about 90% of bladder cancers. Bladder cancer is most often diagnosed in older adults, with a median age at diagnosis of 73.

Urothelial carcinoma also can start elsewhere in the urinary tract, but this is much less common.

Urothelial carcinoma may stay in the inner lining of the urinary tract. Or it may grow into deeper tissues or spread to other parts of the body.

Your healthcare team can help you understand what the cancer's location and other features mean for you.

Types

Urothelial carcinoma of the bladder

Urothelial carcinoma of the bladder starts in the urothelial cells that line the inside of the bladder. It is the most common type of bladder cancer in the United States.

Urothelial tumors of the bladder can grow in different patterns. Papillary urothelial carcinoma grows outward from the bladder lining. Carcinoma in situ (CIS) is a flat, high-grade cancer in the bladder lining. These cancers also may be described as non-muscle invasive or muscle invasive based on how deeply they have grown into the bladder wall.

Upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) starts in urothelial cells in the upper urinary tract. It can form in the renal pelvis or in a ureter. UTUC accounts for about 5% to 10% of urothelial carcinomas.

UTUC is related to urothelial carcinoma of the bladder, but there are important differences in how it is diagnosed and treated. People with UTUC also can develop urothelial carcinoma in the bladder. For this reason, follow-up may include checking the upper urinary tract, which includes the renal pelvis and ureters, as well as the lower urinary tract, which includes the bladder and urethra.

Urothelial carcinoma of the urethra

Urothelial carcinoma also can start in the tube that carries urine out of the body, called the urethra. Cancer that starts in the urethra, also known as primary urethral cancer, is rare. Not all urethral cancers are urothelial carcinoma. Other types include squamous cell carcinoma and adenocarcinoma.

Other types of bladder cancer

Not all bladder cancers are urothelial carcinoma. Less common types include squamous cell carcinoma and adenocarcinoma. Some bladder cancers contain more than one type of cancer cell.

Urothelial carcinoma of the bladder may cause:

• Blood in the urine, called hematuria. This is the most common symptom. The blood may turn urine red or brown. Sometimes, blood does not change the color of the urine. In this situation, blood is found only with a urine test.
• Urinating more often than usual.
• Feeling an urgent need to urinate.
• Pain or burning with urination.

Blood in the urine often is an early warning sign of bladder cancer. Other urinary symptoms, such as frequent or urgent urination and pain with urination, also can occur early.

Pain in other areas can occur when bladder cancer is more advanced or has spread. Depending on the location of the cancer, pain may be felt in the pelvis, belly, side or back.

Symptoms of upper tract urothelial carcinoma

Blood in the urine also is a common symptom of upper tract urothelial carcinoma. Some people have pain in the side of the body between the ribs and hip.

Urothelial carcinoma and urinary tract infections

Some bladder cancer symptoms are like those of a urinary tract infection (UTI). Both illnesses can cause the need to urinate more often, the feeling of an urgent need to urinate, painful urination and, sometimes, blood in the urine. These symptoms can have many causes, so symptoms alone cannot tell whether you have cancer or an infection.

Research has found that bladder cancer took longer to diagnose in women who were first diagnosed with a UTI than in men. It is important to see your healthcare professional if you have lasting or unexplained urinary symptoms.

When to seek care

See a healthcare professional if you have unexplained blood in your urine or urinary symptoms that do not have a known cause. Also seek care if urinary symptoms persist or return after treatment for another suspected cause, such as a UTI.

It's not clear what causes most urothelial bladder carcinomas. Genetic changes in urothelial cells may play a role in how the cancer develops. Some of these changes can cause cells to grow out of control and form a tumor.

Some people inherit genetic changes that raise the risk of urothelial carcinoma. Lynch syndrome is an inherited condition associated with a higher risk of urothelial cancer, particularly upper tract urothelial carcinoma.

Factors that may raise the risk of urothelial carcinoma of the bladder include:

• Smoking. Smoking can raise the risk of bladder cancer by exposing the urinary tract to cancer-causing chemicals that leave the body in urine.
• Age. Bladder cancer can happen at any age, but it is more common in older adults.
• Sex at birth. Men are more likely to get bladder cancer than are women.
• Some chemicals. Regular contact with certain chemicals at work or in the environment may raise the risk. These include arsenic and chemicals used in some dye, rubber, leather, textile and paint industries.
• Certain cancer treatments. Treatment with cyclophosphamide and radiation treatments aimed at the pelvis can raise the risk of bladder cancer.
• Personal or family history. Having had bladder cancer raises the risk of getting it again. A family history also may raise the risk.
• Lynch syndrome. This inherited condition raises the risk of urothelial carcinoma and is especially important in upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) shares several risk factors with bladder urothelial carcinoma, including smoking and some chemical exposures. Kidney stones and Lynch syndrome also are linked to UTUC.

Long-lasting bladder inflammation or infection is associated mainly with squamous cell bladder cancer rather than the more common urothelial type of bladder cancer.

There's no sure way to prevent urothelial bladder carcinoma. These steps may lower the risk of bladder cancer:

• Don't smoke. If you don't smoke, don't start. If you smoke, talk with a healthcare professional about a plan to help you stop.
• Use chemicals carefully. If you work with chemicals, follow workplace safety instructions.

The tests used to diagnose urothelial carcinoma depend partly on where the cancer may be in the urinary tract. Evaluation may include urine tests, imaging, biopsy and procedures to look inside the urinary tract.

Blood in the urine is a common symptom of urothelial carcinoma of the bladder and upper urinary tract. Unexplained blood in the urine should be checked by a healthcare professional.

Cystoscopy

Cystoscopy is a procedure that lets a healthcare professional see inside the urethra and bladder. A small, narrow tube called a cystoscope is passed through the urethra. The cystoscope has a lens that lets the healthcare professional check the urethra and bladder for signs of disease.

Urine tests

A urine cytology test involves looking at a sample of urine with a microscope to check for cancer cells. Urine tests also can find blood that isn't visible. Urine tests are used along with other tests to check for urothelial carcinoma.

Imaging tests

Imaging tests make pictures of the urinary tract. They can help find cancer and show whether it may have spread. A computerized tomography (CT) urogram uses contrast material and CT images to show the kidneys, ureters and bladder. Retrograde pyelography is an X-ray test that uses contrast to show the upper urinary tract.

Biopsy

A biopsy is a procedure to remove a sample of tissue for testing in a lab. For a bladder tumor, your healthcare team may remove tissue during cystoscopy or a procedure called transurethral resection of bladder tumor (TURBT). The tissue can confirm cancer and help determine its type and grade.

Transurethral resection of bladder tumor

Transurethral resection of bladder tumor (TURBT) is a procedure used to diagnose bladder cancer and remove cancers from the inside of the bladder. During TURBT, a healthcare professional passes an instrument through the urethra and into the bladder to remove the tumor. TURBT can provide tissue for diagnosis and also treat many non-muscle invasive bladder cancers.

Diagnosing upper tract urothelial carcinoma

When your healthcare professional suspects that you may have upper tract urothelial carcinoma, you may have tests such as cystoscopy and imaging of the kidneys and ureters. A procedure called ureteroscopy also may be used to look inside the ureter and renal pelvis. During ureteroscopy, your healthcare professional may take a tissue sample, called a biopsy, and collect urine for testing.

The healthcare team also checks the bladder because urothelial cancer can be present there at the same time.

Diagnosing urethral urothelial carcinoma

Tests for suspected primary urethral cancer may include urethrocystoscopy, in which a thin tube with a camera is used to look inside the urethra and bladder. A tissue sample and urine sample also may be tested. Imaging, including MRI, may be used to find out how far the cancer has grown.

Stage and grade describe different things. Stage tells how far the cancer has grown or spread. Grade describes how the cancer cells look and gives clues about how they may behave.

Learn more about urothelial carcinoma stages.

Grades

Urothelial carcinomas are classified by grade. Grade describes how cancer cells look under a microscope. Grade can help show how quickly the cancer may grow or spread.

Urothelial carcinoma does not behave the same way in everyone. Low-grade cancers often grow more slowly, while high-grade cancers are more likely to grow into deeper tissues or spread.

Low-grade urothelial carcinoma

Low-grade urothelial carcinoma has cells that more closely resemble typical cells in appearance and organization. Low-grade bladder cancer tends to grow more slowly and is less likely to grow into the bladder muscle than is high-grade cancer.

High-grade urothelial carcinoma

High-grade urothelial carcinoma has cells that look very different from typical tissue. High-grade bladder cancer tends to grow faster and is more likely to invade the bladder muscle or spread to other tissues and organs. Carcinoma in situ of the bladder is high grade.

Grade also matters in upper tract urothelial carcinoma. Low-grade and high-grade UTUC are managed differently, and grade helps the healthcare team understand the cancer's risk.

Treatment for urothelial carcinoma depends on where the cancer started, its grade and stage, whether it has spread, your overall health and your personal preferences. Treatment may include surgery or other procedures, chemotherapy, immunotherapy, antibody-drug conjugates, targeted therapy, or radiation therapy. Some of these treatments are used together.

Bladder urothelial carcinoma can sometimes be cured. Non-muscle invasive bladder cancer often can be managed with treatments directed at the bladder. Muscle-invasive bladder cancer generally needs more-intensive treatment. For metastatic urothelial carcinoma, treatment may shrink or slow the cancer, ease symptoms, and help people live longer.

TURBT

TURBT is both a diagnostic procedure and a treatment for many non-muscle invasive bladder cancers. A surgeon removes visible tumor through the urethra without making an incision in the abdomen. Medicine may be placed directly into the bladder after TURBT to kill cancer cells that may remain and lower the risk of recurrence.

Intravesical therapy

Intravesical therapy puts medicine directly into the bladder. The treatment may include chemotherapy or immunotherapy. Bacillus Calmette-Guerin (BCG) is an immunotherapy put directly into the bladder. It is used for some intermediate- and high-risk non-muscle invasive bladder cancers. BCG after TURBT can lower the risk that the cancer comes back.

Intravesical treatments can cause bladder irritation and urinary symptoms. BCG also can cause flu-like symptoms and, rarely, more-serious complications.

Cystectomy and urinary diversion

Cystectomy is surgery to remove all or part of the bladder. During a partial cystectomy, only the part of your bladder containing cancer is removed. During a radical cystectomy, the surgeon removes your entire bladder and nearby lymph nodes. The surgeon also may remove nearby reproductive organs.

After radical cystectomy, urinary diversion makes a new way for urine to leave the body. Options may include a neobladder, an ileal conduit that drains to a pouch outside the body or a continent urinary reservoir that is drained through an opening in your abdomen.

Radical cystectomy and urinary diversion can have long-lasting effects on urinary control, sexual function, fertility, bowel function and your body's chemical balance.

Chemotherapy

Chemotherapy uses medicines to kill cancer cells. Chemotherapy may be used for urothelial carcinoma depending on where the cancer started and how advanced it is. For some people who have muscle-invasive bladder cancer and can receive cisplatin, the chemotherapy medicines gemcitabine and cisplatin may be combined with the immunotherapy medicine durvalumab before radical cystectomy. Treatment with durvalumab may continue after surgery. Chemotherapy also can be used with radiation therapy to preserve the bladder or to treat advanced cancer.

Chemotherapy side effects depend on the medicines used. Side effects may include low blood cell counts, infection, mouth sores, hair loss, fatigue and digestive symptoms. Cisplatin also can affect your kidneys, hearing and nerves.

Immunotherapy

Immunotherapy is medicine that helps your immune system fight cancer. It is now an important part of treatment for urothelial cancer, including muscle-invasive bladder cancer. For muscle-invasive bladder cancer, immunotherapy may be combined with chemotherapy or with an antibody-drug conjugate before surgery. The combination treatment may continue after surgery. It also may be used to treat advanced disease. Side effects can affect healthy organs, including your skin, intestines, liver, lungs and hormone-producing glands.

Antibody-drug conjugates

An antibody-drug conjugate combines a cancer-killing medicine with an antibody that attaches to a specific target on cancer cells. Enfortumab vedotin is an antibody-drug conjugate used to treat urothelial cancer, including advanced disease.

For some people with muscle-invasive bladder cancer, enfortumab vedotin may be combined with the immunotherapy medicine pembrolizumab before radical cystectomy and continued after surgery.

Targeted therapy

Targeted therapy uses medicines that target specific features of cancer cells. For advanced urothelial carcinoma, tests may look for gene changes or other tumor features. The results can help show whether targeted therapy may be an option for you.

Radiation therapy and bladder preservation

Radiation therapy treats cancer with powerful energy beams. For selected people with muscle-invasive bladder cancer, bladder-preserving treatment may combine TURBT, chemotherapy and radiation therapy. This approach is sometimes called trimodality therapy. If cancer remains or comes back, radical cystectomy may be needed.

Treatment for upper tract urothelial carcinoma

Treatment for upper tract urothelial carcinoma (UTUC) depends on the cancer's grade and stage, where it is, how large it is, how likely it is to grow or spread, and how well your kidneys are working. Your overall health also affects your treatment choices.

For some low-risk UTUC, treatment may be able to preserve your kidney. A surgeon may use ureteroscopy or another procedure that reaches the tumor through your urinary tract to remove or destroy the cancer. Some low-grade cancers also may be treated with medicine placed directly into your upper urinary tract. These treatments require close follow-up because the cancer can come back.

For some high-risk UTUC, a surgeon may remove the kidney, the entire ureter and a small cuff of bladder where the ureter enters the bladder. This operation is called radical nephroureterectomy. Some people also receive chemotherapy before or after surgery. If UTUC has spread to other parts of your body, treatment usually uses medicines that work throughout your body, similar to treatment for advanced urothelial carcinoma of the bladder.

Treatment for urethral urothelial carcinoma

Treatment of urothelial carcinoma that starts in the urethra depends on its location and how far it has grown. Options may include endoscopic treatment, surgery, chemotherapy, radiation therapy or combinations of treatments. Because primary urethral cancer is rare, treatment is individualized.

After treatment

Urothelial carcinoma may come back even after successful treatment. Follow-up depends on where the cancer started, how likely the cancer is to come back or spread, and the treatment you received. For bladder cancer, follow-up may include cystoscopy, urine tests and imaging. After UTUC, follow-up may include cystoscopy, imaging or a procedure to look inside your remaining upper urinary tract.

Knowing that urothelial carcinoma can come back may cause worry or anxiety. One way to feel more at ease is to ask your healthcare team for a schedule of the tests you will likely need and why you need them. Planning how you may cope with anxiety before follow-up visits also may help. Some tips include:

• Keep your follow-up appointments. Ask what tests you will likely need and how often.
• Talk about your concerns with someone you trust or with your healthcare team.
• Consider connecting with other people who have been treated for bladder or urothelial cancer.

Make an appointment with a healthcare professional if you have symptoms that worry you. You may start with your primary healthcare professional and then be referred to a specialist called a urologist. Depending on your diagnosis and the treatment you need, you also may see specialists in cancer treatment, radiation therapy, medical imaging and lab testing.

What you can do

When you make the appointment, ask whether there is anything you need to do beforehand. Make a list of:

• Your symptoms, including when they started and whether they come and go.
• Personal and family medical history, including cancer history.
• All medicines, vitamins and supplements you take, including doses.
• Questions you want to ask your healthcare professional.

If possible, take a family member, friend or another trusted person with you to help remember the information you get.

Questions to ask

• Where did my urothelial carcinoma start?
• Is the cancer limited to the bladder or another part of the urinary tract?
• What is the grade of my cancer?
• What is the stage?
• If the cancer is in the bladder, is it non-muscle invasive or muscle invasive?
• What treatment options do I have?
• Could treatment cure the cancer?
• What are the possible risks and side effects of treatment?
• What is the chance the cancer will come back?
• Will I need ongoing testing of my bladder or upper urinary tract?
• Should I see a specialist?