Non-muscle-invasive bladder cancer

Non-muscle invasive bladder cancer (NMIBC) is bladder cancer that has not grown into the thick muscle layer of the bladder wall. Because it has not reached the muscle, it is different from muscle-invasive bladder cancer.

About 75% of newly diagnosed bladder cancers are NMIBC. Many people with NMIBC can be treated successfully. But the cancer can come back, and some tumors can grow into the bladder muscle. The chance of this happening depends on features such as the cancer's grade and stage.

Hearing that you have bladder cancer can be worrying. Treatment focuses on removing or destroying the cancer, lowering the chance that it will come back, and helping prevent it from growing into the bladder muscle.

Types

Healthcare professionals describe NMIBC by how the tumor grows and how deeply it has grown into the bladder wall. The main types are Ta, T1 and carcinoma in situ.

• Ta. Ta is a tumor that has stayed in the bladder lining. It has not grown into the tissue below the lining, called the lamina propria.
• T1. T1 is a tumor that has grown into the lamina propria. It has not reached the bladder muscle.
• Carcinoma in situ (CIS or Tis). CIS is a flat, high-grade tumor that stays in the bladder lining.

Blood in the urine, called hematuria, is the most common symptom of bladder cancer. The blood may be easy to see, or it may show up only on a urine test.

Other symptoms can include urinating more often, urinating at night, and pain or burning with urination. These urinary symptoms are more common with CIS.

When to seek care

See a healthcare professional if you have blood in your urine or urinary symptoms that do not go away and have no known cause. These symptoms can have causes other than cancer, but they should be checked.

Bladder cancer can happen after changes in cells that line the bladder. Certain exposures can raise the risk of these changes. These include tobacco smoke and some workplace chemicals. Other risk factors include prior pelvic radiation, some medicines, and long-term bladder irritation or infection.

The following factors are linked to a higher risk of bladder cancer.

• Tobacco use, especially cigarette smoking.
• Older age.
• Contact with some chemicals at work, including chemicals used in dyes, rubber, paint, metals and petroleum.
• Past treatment with pelvic radiation or some chemotherapy medicines, including cyclophosphamide.
• Long-term bladder irritation or infection, including some parasitic infections and long-term catheter use.
• A personal or family history of bladder cancer and some inherited genetic conditions.

Some NMIBC can progress. Progression means the cancer grows into the bladder muscle or becomes more advanced. The risk of progression depends on features such as the tumor's grade and stage and whether CIS is present.

There is no sure way to prevent bladder cancer. Smoking is the most important known risk factor. Some workplace chemical exposures also are linked to a higher risk.

Healthcare professionals diagnose bladder cancer by looking inside the bladder and testing tumor tissue. They also may use urine tests and imaging tests.

Cystoscopy

Cystoscopy uses a thin tube with a light and lens to look inside the bladder and the tube that carries urine out of the body, called the urethra. Cystoscopy is the main test used to look for bladder tumors.

Urine tests

A urine cytology test checks a urine sample for cancer cells. Urine cytology is better for finding high-grade tumors, including CIS, than for finding low-grade tumors.

Imaging

A computerized tomography (CT) urogram can make pictures of the kidneys, ureters and bladder. Imaging also can help with staging when a cancer may be high grade or invasive.

Transurethral resection of bladder tumor

If you have a tumor, a procedure called transurethral resection of bladder tumor (TURBT) can remove the visible tumor through the urethra. The tissue is then tested to find the tumor's grade and how deeply it has grown into the bladder lining.

Sometimes, you may need a second TURBT. This may happen if the first procedure was not complete or for some high-grade tumors, especially T1 disease.

Grades

Grade describes how cancer cells look under a microscope. It also gives clues about how the cancer may act. NMIBC is usually described as low grade or high grade.

• Low-grade cancers. These cancers often come back after treatment. But they rarely grow into the bladder muscle or spread to other parts of the body.
• High-grade cancers. These cancers are more likely to come back, grow into the bladder muscle and spread. CIS is high grade.

Treatment depends on more than the grade and stage. Your healthcare team also looks at the number and size of tumors and whether CIS is present. Together, these features help place NMIBC into a risk group. Risk groups help guide treatment and follow-up.

Risk groups

• Low-risk NMIBC. This group usually includes a small, single, low-grade Ta tumor.
• Intermediate-risk NMIBC. This group has features between low and high risk, such as having several tumors or cancer that has come back.
• High-risk NMIBC. This group includes cancers more likely to progress, such as CIS or high-grade T1 disease.

Risk groups are not the same as cancer stages. Risk groups use stage, grade and other tumor features to estimate the chance that NMIBC will come back or progress.

Transurethral resection of bladder tumor

TURBT is the first treatment for most visible NMIBC tumors. The surgeon removes as much of the visible tumor as possible through the urethra. The tissue is tested to confirm stage and grade.

Intravesical chemotherapy

Intravesical treatment puts medicine directly into the bladder through a thin tube called a catheter. Chemotherapy given this way can lower the chance that cancer will come back, especially for low- and intermediate-risk disease.

BCG immunotherapy

Bacillus Calmette-Guerin (BCG) is an immunotherapy put directly into the bladder. It helps the immune system attack bladder cancer cells. BCG is a standard treatment for many intermediate- and high-risk NMIBCs.

For high-risk NMIBC, BCG often is given as a first course followed by maintenance treatment. Maintenance may last 1 to 3 years depending on your risk and treatment plan.

Some people with high- or very-high-risk NMIBC who have not had BCG before may receive durvalumab, a type of immunotherapy. It is added to BCG with maintenance. More study is needed to understand its long-term benefits and risks.

When BCG does not work

If high-risk NMIBC comes back after BCG treatment, the care team considers how much BCG you received, when the cancer came back and how it responded to treatment. These factors help guide the next treatment recommendation. High-grade cancer that comes back within set time periods after enough BCG treatment may be called BCG-unresponsive NMIBC.

For many people, removing the bladder with radical cystectomy is the preferred treatment. Bladder-preserving treatments and clinical trials may be options for people who cannot have or do not want cystectomy.

Bladder-preserving choices include medicines put into the bladder and, sometimes, immunotherapy given through the bloodstream. Nadofaragene firadenovec (Adstiladrin) is a gene therapy put directly into the bladder. Pembrolizumab is an immunotherapy that may be used for some people with high-risk BCG-unresponsive NMIBC.

Cystectomy

Radical cystectomy is surgery to remove the bladder. It may be recommended for very-high-risk NMIBC or high-grade disease that does not respond to BCG. The decision weighs the risk of cancer progression against the risks and effects of major surgery.

Follow-up and surveillance

NMIBC often comes back, so follow-up after treatment is important. The first follow-up cystoscopy is typically done three months after TURBT for people with Ta, T1 or CIS.

After that, the timing of follow-up depends on the person's risk group. People who have high-risk disease need closer and longer follow-up than do those with low-risk disease.

Follow-up may include cystoscopy, urine cytology and imaging of the upper urinary tract. Which tests are used depends on risk.

Make an appointment with a healthcare professional if you have any symptoms that worry you. You likely will start by seeing your primary care team. But you might be referred to a doctor who specializes in treating diseases and conditions of the urinary tract, called a urologist. Sometimes, you may be referred to other specialists, such as a doctor who treats cancer, called an oncologist. Here are some tips to get ready for your appointment.

What you can do

When you make the appointment, ask if there's anything you need to do before your appointment, such as not eating or drinking for a certain amount of time. Make a list of:

• Your symptoms, including any that don't seem related to the reason for your appointment.
• Key personal information, including major stresses, recent life changes and family medical history.
• All medicines, vitamins and other supplements you take, including the doses.
• Questions to ask your healthcare professional.

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

For bladder cancer, basic questions to ask your healthcare professional include:

• Do I have bladder cancer, or could my symptoms be caused by another condition?
• What tests do I need?
• What is the stage of my cancer?
• What are my treatment options?
• What treatments might cure bladder cancer?
• What are the possible risks of each treatment?
• Should I see a specialist?
• Is there a generic alternative to the medicine you're prescribing?
• Do I need follow-up appointments?
• Are there brochures or other printed material that I can take with me? What websites do you recommend?

Be sure to ask any other questions you may have.

What to expect from your care team

Your healthcare professional is likely to ask you questions, such as:

• When did your symptoms start?
• Are your symptoms always present, or do they come and go?
• How bad are your symptoms?
• What, if anything, makes your symptoms better?
• What, if anything, makes your symptoms worse?

Stage and grade mean different things. Grade describes how the cancer cells look and how they may act. Stage describes how deeply the tumor has grown into the bladder lining. Both help guide treatment.

NMIBC includes stages 0a, 0is and 1. In these stages, the cancer has not grown into the bladder muscle.

• Stage 0a, noninvasive papillary cancer, also called Ta. The tumor has stayed in the bladder lining.
• Stage 0is, carcinoma in situ (CIS), also called Tis. CIS is a flat, high-grade cancer in the bladder lining.
• Stage 1, T1 bladder cancer. The cancer has grown into tissue under the bladder lining but has not reached the muscle layer.

Survival rates describe what has happened in large groups of people. Survival rates cannot predict exactly what will happen to you.

For high-grade NMIBC, cancer-specific survival is about 70% to 85% at 10 years. Survival is higher for low-grade disease. Cancer-specific survival is the percentage of people who have not died from the cancer during a set time.

The National Cancer Institute reports a five-year relative survival rate of 97% for carcinoma in situ of the bladder alone.

Broader survival categories, such as localized bladder cancer, are not the same as Ta, T1 or NMIBC risk groups.

Survival statistics are based on people treated in earlier years. So they may not fully show the effects of newer treatments.