Bladder Cancer

What Happens Under Normal Conditions?

The bladder is a hollow balloon-shaped, mostly muscular, organ that stores urine until ready for release. The urine is produced in the kidneys. It flows through tubes called the ureters into the bladder and is discharged through the urethra during urination. The bladder muscle aids urination by contracting (tightening) to help force out the urine.

A thin surface layer called the urothelium lines the inside of the bladder. Next is a layer of loose connective tissue called the lamina propria. Covering the lamina propria is the bladder muscle. Outside of the bladder is a layer of fat.

What is Bladder Cancer?

When the cells in our body don’t act in the way they should, it can lead to abnormal growth or cancer. Bladder cancer is cancer that originates in the bladder, with patients developing one or more tumors comprised of abnormal cells.

There are two distinguishing forms of bladder cancer:

• Non-muscle invasive bladder cancer (NMIBC): This form of bladder cancer occurs in the tissue along the inside surface of the bladder. Unlike MIBC, the bladder muscle is unaffected and the tumor is isolated to the bladder.
• Muscle invasive bladder cancer (MIBC): Unlike NMIBC, this form of cancer has spread to the muscle in the wall of the bladder. Because this is an advanced form of bladder cancer, it requires urgent treatment.

What Causes Bladder Cancer?

The ways in which bladder cancers develop and progress are only partly understood. However, a number of substances that cause the cancers to develop have been identified.

• Cigarette smoke: Cigarette smoking alone has been estimated to cause 50 percent of all bladder cancer cases in the United States.
• Individuals exposed to long-term secondhand smoking, may also be at risk
• Radiation around the pelvis
• Genetics
• Various industrial chemicals: Long-term workplace exposure to chemical compounds such as paints and solvents has been estimated to cause another 20 to 25 percent of bladder cancer cases.

Carcinogens, or cancer-causing agents, in the blood stream are filtered out by the kidneys to eliminate them from the body. However, these carcinogens remain in the bladder for a few hours interacting with the lining of the bladder before they are removed by urination. Through this process the bladder becomes a high risk organ for cancer, particularly in smokers.

More than 90 percent of all bladder cancers originate in the urothelium, the inner lining of the bladder.

What Are Risk Factors for Bladder Cancer?

Smokers develop bladder cancer at two to three times the rate of non-smokers. People who work with dyes, metal, paints, leather, textile and organic chemicals may be at a higher risk. People who have chronic bladder infections may also be at higher risk.

What are the Symptoms of Bladder Cancer?

• Blood in the urine (hematuria), may be visible or microscopic
• Frequent urinary tract infections, for which the cause has not been found
• Frequent urination or burning with urination in the absence of an infection
• Pain in lower abdomen or back

It is important to remember that these symptoms do not on their own indicate or confirm the presence of bladder cancer. These are also common symptoms of other issues such as kidney stones or urinary tract infections. We will do a thorough and complete evaluation if you complain of these symptoms, in order to exclude the possibility of bladder cancer.

How is Bladder Cancer Diagnosed?

History and Physical Exam – We will ask the patient about past exposure to known causes of bladder cancer, such as cigarette smoke (either through personal smoking or through “second-hand” smoke) or chemicals. We will also evaluate your symptoms if you have any.

Urine Cytology – With cytology, the urine is examined under a microscope to look for cancer cells that may have been shed into the urine from the bladder lining. Urine can also be tested for substances known to be closely associated with cancer cells (tumor markers).

CT scan – Because blood in the urine can come from anywhere in the urinary tract, we typically order radiological imaging of the kidneys, ureter and bladder to check for problems in these organs.

Cystoscopy – Cystoscopy is the most important diagnostic tool. It is an in-office procedure, in which a fiber-optic camera is inserted through the urethra into the bladder. The camera allows for direct visualization inside the bladder to look for any tumors, masses, or any other abnormalities. Modern cystoscopes are soft and flexible, and this procedure is generally well tolerated.

If tumors are present on the cystoscopy, the doctor notes their appearance, number, location and size. As removal (resection) of the tumors cannot usually be done under local anesthesia, the patient is then scheduled to return for a surgical procedure to remove the tumor under general anesthesia. In a manner as before, the doctor inserts an instrument, called a resectoscope, into the bladder. This is a viewing instrument similar to the cystoscope, but contains a wire loop at the end for removing tissue. This procedure is done through the urethra and is called a transurethral resection of bladder tumor or “TURBT”. The removed tissue is sent to a pathologist for examination.

Tumor Staging and Grading – If a biopsy is taken and bladder cancer is found, the pathologist who examines the tissue will grade the tumor according to how aggressive the cells appear. The most widely used grading systems classify tumors into two main grades: low and high. The cells of low-grade tumors have minimal abnormalities. In high-grade tumors, the cells have become disorganized and many abnormalities are apparent. The grade indicates the tumor’s “aggression level”—how fast it is likely to grow and spread. High-grade tumors are the most aggressive and the most likely to progress into the muscle. Staging of bladder cancers is based on how deeply a tumor has penetrated the bladder wall.

Table 1 lists stages of penetration using the TNM classification system:

How is Bladder Cancer Treated?

Treatment options are dependent on the form of bladder cancer that’s been diagnosed.

For patients with NMIBC, the main treatment options include:

• Cystoscopic transurethral resection (TURBT)
• Intravesical immunotherapy
• Intravesical chemotherapy

For patients with MIBC, the main treatment options include:

• Bladder removal or cystectomy (either radical cystectomy or partial cystectomy)
• Cystectomy with chemotherapy
• Chemotherapy with radiation as well as TURBT

Below is more information about each type of treatment:

TURBT – Transurethral resection of the bladder, is the usual treatment method for patients who, when examined with a cystoscope, are found to have abnormal growths in the bladder. Also explained above.

Intravesical chemotherapy and immunotherapy – Following removal, intravesical chemotherapy or immunotherapy may be used to try to prevent tumor recurrences. Intravesical means “within the bladder”. These therapeutic agents are put directly into the bladder through a catheter in the urethra (the catheter only stays in for a few minutes), are retained for one to two hours and are then urinated out.

The chief intravesical agents currently available are thiotepa, doxorubicin, mitomycin C and bacillus Calmette-Guérin (BCG). The first three are chemotherapy drugs. The fourth, BCG, is a live but weakened vaccine strain of bovine tuberculosis. It was first used to immunize humans against tuberculosis. It is now one of the most effective agents for treating bladder cancer.

Each of the four agents may produce irritative side effects such as painful urination and the need to urinate frequently. In addition, BCG therapy carries a 24 percent risk of flu-like symptoms.

Once the grade and stage of the tumor has been determined, the urologist may decide to initiate a course of intravesical therapy with these agents. In general, six weekly treatments are given, in which a catheter is placed in the bladder, the medication is instilled, the catheter is removed, and the patient is instructed not to urinate for at least an hour. Periodic cystoscopies and urine tests are required to detect tumor recurrence early, if it is going to develop. During the first one to two years surveillance is carried out on a quarterly basis but then can gradually be reduced to twice and eventually even once per year thereafter.

Cystectomy – Surgical removal of the entire bladder may be an option for patients with high-grade cancers that have persisted or recurred after intravesical treatments. There is a substantial risk of progression to muscle-invasive cancer in such cases, and some patients may want to consider cystectomy as a first choice of treatment. If so, they should ask their doctor for information about both the risks of cystectomy and the methods of urinary reconstruction (“urinary diversion”).

Radiation – Radiation is typically performed in conjunction with chemotherapy and TURBT. Therapy consists of using high-energy rays to attack cancer cells.

What are Some Side Effects of Bladder Cancer Treatment?

Every patient will respond differently to treatment however some common side effects following surgery include:

• Pain or discomfort
• Problems with urinary diversion, i.e.: leak from a stoma
• Gastrointestinal problems
• More frequent urination – specifically after TURBT or intravesical treatments

What Can I Expect After Treatment?

It is critical to stay in touch with your doctor even when treatment is over.

For patients who were treated for NMIBC, we typically schedule a follow-up cystoscopy 3-4 months to see check for reoccurrence. From here, your risk for reoccurrence will determine your follow-up frequency:

• If you’re at low risk for reoccurrence, we will typically ask you to return in three months.

If you’re at a middle or intermediate risk of reoccurrence, we typically perform a cystoscopy and cytology every 3-6 months for two years. From here, we’ll perform a cystoscopy and cytology every 6-12 months for 3-4 years then annually.

• High-risk patients will be asked to return every 3-4 months for 2 years, every 6 months for 3-4 years, then annually.

Patients treated for MIBC will need to visit their doctor regularly. Your doctor will determine a follow-up plan that might include lab work and/or imaging tests.

Do Bladder Tumors Occur in Children?

Fortunately, bladder tumors are rare in children.

Are There Screening Tests for Early Detection of Bladder Cancer?

Not at this time, although periodic check of the urine for microscopic blood may promote earlier detection.