Bladder cancer is an uncontrolled growth of abnormal cells in the bladder, the balloonlike organ that stores urine.

Bladder cancer begins in the lining of the bladder. In 70% to 80% of people with bladder cancer, the cancer is discovered when it is still a limited, superficial problem. These superficial bladder cancers usually appear as an isolated patch of abnormal cells on the bladder lining or as an odd, fingerlike projection along the bladder's inner wall. Less often, the tumor is diagnosed when it already has become invasive, which means the tumor has invaded deeply into the muscle of the bladder wall, spread (metastasized) to nearby lymph nodes or spread to distant organs.

There are three types of bladder cancer, which have different types of cells. About 90% of cancers in the bladder are transitional cell carcinomas. The rest are either squamous cell carcinomas (6% to 8%) or adenocarcinomas (2%).

The causes of bladder cancer are only partly understood. It is thought that the majority of transitional cell carcinomas are caused by carcinogens (cancer-causing substances), such as tobacco smoke and chemicals in the environment. Smokers get bladder cancer two to four times more often than people who don't smoke, although only about half of all bladder-cancer patients have ever been smokers. Bladder cancer also is associated with exposure to certain industrial chemicals, but exposure to such chemicals has been reduced dramatically by modern workplace safety laws. These industrial carcinogens include aniline dyes, polycyclic aromatic hydrocarbons (such as 2-naphthylamine, 4-aminobiphenyl or benzidine), polychlorinated biphenyls or chemicals used in aluminum manufacturing. These chemicals are used in the aluminum, rubber, chemical and leather industries, as well as by dry cleaners, chimney sweeps, hairdressers, painters, printers, textile workers, machinists and truck drivers. In developing countries, a parasitic infection called schistosomiasis increases the risk of developing bladder cancer.

Bladder cancer tends to return in people who have had the disease. After bladder cancer is treated, there is a significant likelihood that additional cancers will occur in other locations either within the bladder itself, in the ureters (the tubes that drain the urine from the kidneys into the bladder) or in the part of the kidney called the renal pelvis. The risk of additional cancers developing elsewhere in the urinary tract means that once you have had one episode of bladder cancer, you need to be monitored.

In the United States, bladder cancer is the fourth most common cancer among men and the ninth most common among women. About 63,000 new cases are diagnosed each year, most of them in adults older than 55. Caucasians are two times more likely to develop bladder cancer than are African-Americans, and the illness is three times more likely to affect men than women. Bladder cancer kills approximately 13,000 Americans each year.

Symptoms of bladder cancer include:

• Blood in the urine (hematuria) � This symptom is the first sign of bladder cancer in 80% to 90% of people. Hematuria may appear as an obvious red color in the urine, or it may turn the urine a rusty color.
• Painful urination, called dysuria
• Frequent urination, more often than normal

Your doctor will review your medical history, especially any history of kidney stones or urinary tract infections, because these conditions also can cause blood in the urine. Your doctor also will ask about your history of cigarette smoking, your occupation and your diet.

If you don't smoke now, but did in the past, it is important to tell your doctor. Even though you have quit smoking, your risk of bladder cancer remains high for more than 10 years after your last cigarette.

After reviewing your symptoms and risk factors, your doctor will examine you, including a rectal examination and, in women, a pelvic examination. Your doctor also will order laboratory tests, including blood tests and urine tests to check for microscopic amounts of red blood cells and infection. In addition, a urine sample may be sent to a special lab to look for atypical cells and cancer cells.

The main test when looking for bladder cancer is cystoscopy, a procedure in which your doctor inserts a medical instrument through your urethra into your bladder so that he or she can look at the lining of your bladder. Your urethra is the opening through which you urinate. With cystoscopy, your doctor can see whether there are tumors growing in the bladder. During cystoscopy, your doctor either will take a biopsy of the tumor or remove it entirely, if that is possible. A biopsy involves cutting out a small piece of tissue so that it can be examined under a microscope to look for cancer cells. In many cases, two cystoscopies will be done, the first to take a biopsy and determine whether cancer is present and the second to remove any cancer that was found during the first procedure.

In some cases, additional tests may be necessary to determine how far the cancer has spread. At the very least, your doctor should examine the ureters and the renal pelvises, which are the parts of the kidneys where urine collects before draining into the bladder. This can is done in one of three ways:

• A special X-ray test called an intravenous pyelogram (IVP) � In an IVP, dye is injected into the blood and X-rays are taken of the kidneys and ureters as the dye filters through the kidneys and drains into the bladder. An IVP is done to look for other tumors in the upper urinary tract.



• A special computed tomography (CT) scan called a CT urogram � A CT urogram creates computerized, three-dimensional images that allow a doctor to see the ureters clearly.



• A retrograde pyelogram � This test is similar to an IVP, but it is done by a urologist during cystoscopy. Instead of the dye being injected into the bloodstream, the urologist injects dye directly into the ureters during cytoscopy.

If your urologist suspects a problem, he or she may do a test called ureteroscopy. In this test, he or she inserts a small scope into the ureters and renal pelvises to look at them directly instead of only on X-rays. Other tests may include an ultrasound, CT scan or magnetic resonance imaging (MRI) scan, which allow your doctor to see the bladder wall as well as the kidneys and the lymph nodes near the bladder.

Once it develops, bladder cancer will continue to grow and possibly spread until it is treated.

To reduce your risk of bladder cancer, don't smoke. If you already smoke, ask your doctor about proven ways to help you quit.

If you work in an occupation in which there is a high risk of exposure to chemicals that can cause bladder cancer, find out about the types of equipment that are available to reduce your exposure, then use this equipment faithfully while you are on the job. If you need more information about specific types of exposure or specific protective equipment, contact the National Institute for Occupational Safety and Health (NIOSH). NIOSH is part of the U.S. Centers for Disease Control and Prevention. It also is believed that people who drink plenty of water every day have a lower risk of bladder cancer than people who drink only a small amount of fluids. The water is thought to make carcinogens in the urine less concentrated.

Treatment of bladder cancer depends on how aggressive the cancer appears under a microscope, called the tumor grade, and how much it has spread, called the tumor stage.

Tumor grade
The tumor grade is an estimate of how likely the cancer is to grow and spread rapidly. Bladder cancer is classified as high grade if it appears aggressive and has a high potential to spread and become life threatening if not treated early. High-grade cancers often need to be treated with chemotherapy, radiation or surgery. Low-grade cancers appear non-aggressive and have less than at 5% chance of becoming high grade. Low-grade bladder cancers do not behave like true cancers in the vast majority of people. In other words, bladder cancer can be thought of as two different diseases: low-grade cancers and high-grade cancers. Low-grade tumors tend to come back and, if they do, they may need to be removed repeatedly. However, they are rarely life threatening, and aggressive treatments, such as radiation or removing the bladder, usually are not needed.

Tumor stage
The stage is determined by three factors:

• Whether the tumor involves only the bladder lining, or whether it has invaded the bladder muscle, tissues around the bladder or nearby pelvic organs
• Whether the cancer has spread to nearby lymph nodes
• Whether the cancer has spread (metastasized) to distant sites in other areas of the body

Treatment options vary depending on the stage:

Superficial tumors
Superficial tumors are cancers that involve only the bladder lining. These tumors usually are low-grade tumors and usually are treated with a procedure called a transurethral resection (TURBT), done through a cystoscope. In this procedure, the doctor uses either a small wire loop to remove the tumor or a localized electric current to burn it away (a process called fulguration). After transurethral resection, some high-risk patients (patients with high-grade tumors or recurring low-grade tumors) also receive medications placed inside the bladder. This treatment, called intravesical therapy, uses one of the following drugs: bacillus Calmette-Guerin, also called BCG (Pacis, TheraCys, TICE BCG); thiotepa (sold as a generic); mitomycin (Mutamycin); interferon; or doxorubicin (Adriamycin, Rubex).

Intravesical therapy can reduce the likelihood that the cancer will return, and it may reduce the likelihood that the cancer will progress to a more advanced and dangerous stage.

Treatment options are less clear for superficial high-grade tumors that return despite transurethral resection and intravesical therapy. When high-grade superficial tumors return more than once or twice, many experts recommend surgery to remove the bladder. This is a major operation. For older patients with other medical illnesses, doctors might suggest radiation and intravenous chemotherapy instead.

Carcinoma in situ
Carcinoma in-situ is a form of noninvasive bladder cancer. Carcinoma in situ refers to cancer that exists only within the very thin, most superficial membrane lining the bladder. It does not grow outward into the bladder's cavity or inward to invade the tissue underneath the superficial membrane. Carcinoma in situ is more likely than other superficial cancers to spread to other sites in the body. Carcinoma in situ can be difficult to remove completely because it is a flat tumor that can be hard to see, and it can involve multiple areas of the bladder. Intravesical therapy with BCG can eliminate carcinoma in situ in some people. If BCG and transurethral resection fail to eliminate carcinoma in situ, then doctors usually recommend that the bladder be removed surgically to prevent the cancer from spreading to other parts of the body. Radiation and chemotherapy are not effective against carcinoma in situ.

Tumors invading the bladder muscle
In this case, bladder cancer has grown into the thick muscle of the bladder wall, but has not spread to the lymph nodes or distant organs. The standard treatment is a type of surgery called radical cystectomy, which removes the bladder, together with nearby lymph nodes and adjacent pelvic organs. In men, this procedure includes removal of the prostate gland and seminal vesicles. In women, it includes removal of the uterus, fallopian tubes, ovaries and part of the vagina. Because a radical cystectomy removes the bladder, the surgeon must create an alternate way for the body to hold and pass urine. In some patients, the surgeon will use part of the small bowel to create a tube that drains the urine from the ureters to an opening in the abdomen called a stoma. The urine is collected in a bag that covers the stoma. An alternative is to use part of the intestine to construct a new storage area for urine (this is called either a Koch pouch or a Mainz or Indiana pouch). This pouch is then connected to a stoma that is constructed in such a way that the urine cannot leak out unless a catheter is inserted through it. This is called a continent stoma because it is designed not to leak urine. In other cases, the surgeon will create a pouch that he or she can connect to the urethra so that urine leaves the body through the same opening as it did before the surgery. Such a pouch is called a neobladder. Which alternative is best for you depends on your circumstances and your personal preferences. Each procedure has advantages and disadvantages.

Some cancer doctors recommend giving chemotherapy before radical cystectomy, but this is controversial. There is evidence that the cancer is less likely to return in some of the patients who receive chemotherapy prior to the surgery, and that these patients live longer. Since cancer doctors cannot predict which patients will get this benefit, many patients need to be treated to improve the outcome of a few. The other approach is to remove the bladder without giving chemotherapy first. After the bladder is removed, it can be examined to determine if a patient's cancer is likely to return and if chemotherapy should be done. However, it is unclear whether giving chemotherapy after surgery provides the same benefit as chemotherapy prior to surgery.

As an alternative to radical cystectomy, a procedure called a segmental or partial cystectomy is sometimes used in people who have very localized, less aggressive tumors (about 5% to 10% of cases). In a segmental cystectomy, only the diseased portion of the bladder is removed, so the patient can still urinate more or less normally after the procedure. A disadvantage of this procedure is that the bladder is smaller afterward and you may need to urinate frequently.

One alternative to surgery is radiation therapy combined with chemotherapy. Many studies of this approach have been done and favorable results have been reported, although only certain patients are eligible for this approach. The advantage of this approach is that about half of all patients treated this way can keep their own bladders. However, it is not clear whether radiation therapy combined with chemotherapy is as effective as surgery. Therefore, this approach is not widely accepted in the United States. However, if a patient is not a good candidate for any type of surgery, then radiation therapy, usually combined with chemotherapy, should be considered.

More extensive tumors
Tumors that have invaded beyond the bladder wall are usually treated with radical cystectomy if the entire tumor can be removed. If the tumor cannot be removed, chemotherapy or radiation therapy sometimes is given prior to surgery to try to shrink the tumor so that it can be removed. If cancer has invaded through the bladder wall at the time of surgery or if it has spread to lymph nodes, then chemotherapy after surgery may reduce the likelihood that the cancer will come back later. However, bladder cancers that have spread to lymph nodes usually cannot be cured.

Metastatic bladder cancer
Bladder cancer that has spread to other organs or to distant lymph nodes is considered metastatic. Metastatic bladder cancer is usually fatal. However, it is very sensitive to chemotherapy and there is strong evidence that chemotherapy can prolong the lives of patients with metastatic bladder cancer. Most patients will have their tumors shrink at least partially with chemotherapy. A small number of patients may even be cured. The standard chemotherapy used for this purpose was, until recently, a combination of four drugs: methotrexate (sold as a generic), vinblastine (Velban), doxorubicin (Adriamycin, Rubex) and cisplatin (Platinol). This combination is referred to as MVAC. However, a recent study showed that a two-drug combination of gemcitabine (Gemzar) and cisplatin is roughly equivalent and is better tolerated. Other drugs commonly used to treat bladder cancer include paclitaxel (Taxol), ifosfamide (IFEX) and carboplatin (Paraplatin).

Call your doctor immediately if you notice blood in your urine, or if your urine turns the color of rust. Also, call your doctor if you begin to urinate more often than normal, or if urination is painful or uncomfortable in any way.

The outlook depends on the stage of bladder cancer and the type of treatment used. Overall, up to 80% of people with superficial tumors survive for at least five years after diagnosis. For people whose tumors have invaded the bladder muscle, the five-year survival rate may be as high as 75%. People with more invasive tumors or metastatic tumors generally have a poorer outlook, with five-year survival rates of 40% or less.

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