Also called: Urinary Bladder Cancer, Superficial Bladder Cancer, Transitional Cell Carcinoma
Mark Oren, M.D., FACP
Bladder cancer is characterized by an overgrowth of abnormal cells in the bladder, a hollow pelvic organ that stores urine. Unlike healthy cells, which divide and grow in an organized manner, cancer cells continue to divide in an uncontrolled fashion until they form a mass called a tumor.
The bladder is composed of many different layers of cells. Most bladder cancers begin in the inner lining layer called the urothelium. However, this disease can invade other layers of the bladder and spread to surrounding tissues and other bodily organs.
The three main types of bladder cancer include:
- Urothelial carcinoma
- Squamous cell carcinoma
According to the American Cancer Society (ACS), bladder cancer is the fifth leading cancer in the United States. The exact cause of this disease remains unknown. However, risk factors such as smoking, increased age and exposure to certain chemicals may increase an individual’s likelihood of developing the disease. Common signs and symptoms of bladder cancer may include blood in the urine, changes in bladder habits and inability to urinate.
To diagnose bladder cancer, a urologist (a physician who specializes in disorders of the urinary system and male sex organs) may perform a cystoscopy. This procedure uses a thin, lighted tube called a cystoscope, which allows the physician to view the inside of the bladder. If abnormal tissue is detected, a sample is removed (biopsy) and is examined by a pathologist. Surgery alone or with other treatments, such as radiation therapy and chemotherapy, is used to treat the majority of bladder cancer cases. When bladder cancer is detected and treated early, there is a very good chance for survival.
About bladder cancer
Bladder cancer occurs when the cells in the bladder (a hollow pelvic organ that stores urine. Unlike normal cells, which divide and grow in an organized fashion, the cancer cells continue to divide until they form a growth or tumor (a mass of excess tissue). In some cases, the cancer cells even become invasive, spreading from the bladder lining (where they originate) through the bladder wall and into neighboring lymph nodes and organs. Over time, bladder cancer can spread to distant sites such as the lungs, liver and bones.
The bladder is a muscular organ located in the pelvis. It stores urine, which is produced when the kidneys filter the blood. The bladder can become smaller or larger depending on how much urine it holds. The average adult bladder can hold approximately 16 ounces (473 milliliters) of urine. Urine from the kidneys passes into the bladder through two thin tubes called ureters, and is eliminated from the body through a third tube called the urethra. In women, the urethra is very short and ends right in front of the vagina. A man’s urethra is longer because it runs through both the prostate gland and the penis.
The bladder is composed of many layers of cells. Most bladder cancers begin in the urothelium. Also called the transitional epithelium, this layer of urothelial cells lines the inside of the urethra, bladder, ureters and kidneys. In addition to the urothelium, bladder cancer can also affect other cell layers such as muscle and connective tissue in and around the bladder. Bladder cancer usually begins in the lining layer and then can grow into the bladder wall. As the cancer reaches the deeper layers, it becomes more serious and difficult to treat.
When patients are initially diagnosed with bladder cancer, the disease is confined to the bladder in approximately 74 percent of the cases. In 19 percent of cases, the cancer has spread to tissues around the bladder, and in 3 percent of cases, it has reached distant sites (metastasis).
According to the American Cancer Society (ACS), more than 67,000 new cases of bladder cancer will be diagnosed in the United States during 2007. In addition, almost 14,000 individuals will die of the disease. Despite the increased incidence, the rate of bladder cancer deaths is decreasing. In fact, there are more than 500,000 bladder cancer survivors in the United States today.
Bladder cancer occurs nearly four times more often in men than in women. Additionally, white people are diagnosed with bladder cancer nearly twice as often as black people, and Hispanics have the lowest bladder cancer rate of the three groups. Bladder cancer tends to affect elderly people. In fact, half of all bladder cancer patients are over the age of 73.
When this disease is detected and treated early, there is a very good chance for survival. Individuals who are diagnosed with bladder cancer when it is localized have a 94 percent 5-year survival rate. After the disease has spread regionally, survival drops by about half. Left untreated, bladder cancer can lead to additional medical complications and a poorer prognosis for recovery.
Types and differences of bladder cancer
There are three basic types of bladder cancer, which are named for the type of cells that become cancerous (malignant).
More than 90 percent of bladder cancers are classified as urothelial carcinoma, which is also known as transitional cell carcinoma (TCC). Urothelial carcinoma has several subtypes, which are named according to the shape of the cancer cells (flat or with papillary projections) and whether the cells are invasive or noninvasive. These subtypes include:
- Noninvasive urothelial tumors. The cancer affects only the urothelium (the innermost layer of a patient’s bladder wall) and has not spread to other layers of the bladder wall.
- Invasive urothelial tumors. The cancer has spread to other layers of the bladder wall.
- Superficial urothelial tumors. This category includes noninvasive bladder cancers, as well as some invasive cancers that have not spread into the deeper layers of the bladder wall.
- Papillary urothelial tumors. These tumors have slender projections that resemble fingers and may be further subdivided into other types.
- Flat urothelial tumors. Flat urothelial tumors can invade either close to the hollow center of the bladder or the bladder wall’s deeper layers.
In addition to urothelial tumors, the other two types of bladder cancer include:
- Squamous cell carcinoma. This type of bladder cancer, from another type of lining cell, is usually invasive, and far less common than urothelial carcinoma. Squamous cell carcinoma accounts for approximately 4 percent of bladder cancers, according to the ACS.
- Adenocarcinoma. This type of bladder cancer, from the glands in the bladder, is also much less common than urothelial carcinoma, and tends to invade other organs. The ACS maintains that just 1 to 2 percent of bladder cancers are adenocarcinomas.
Though other types of bladder cancer do exist, they tend to be very rare. Individuals can also develop a number of benign bladder tumors, which are typically removed by surgery and do not pose any health risks.
Risk factors and causes of bladder cancer
Though the exact cause of bladder cancer remains unknown, certain risk factors have been identified which increase an individual’s likelihood of developing the disease. Risk factors associated with bladder cancer include:
- Age. The risk of developing bladder cancer increases with age. According to the American Cancer Society (ACS), about 70 percent of bladder cancer cases occur in patients age 65 or older.
- Gender. Men have a four times greater chance than women to develop bladder cancer.
- Smoking. Individuals who smoke develop bladder cancer twice as often as nonsmokers. According to the ACS, smoking is associated with 48 percent of bladder cancer deaths among men and 28 percent of bladder cancer deaths among women. The lungs absorb certain chemicals from tobacco. These chemicals are then passed into the bloodstream, filtered by the kidneys and collected in the urine. When these chemicals accumulate in the urine, they can damage the cells that line the bladder and thereby increase the risk of bladder cancer. In addition to tobacco, marijuana smoking has also been associated with a higher risk of bladder cancer.
- Work exposure. Certain types of jobs may increase an individual’s risk of developing bladder cancer because the employee is exposed to certain chemicals during the course of duty or in the workplace. For instance, hairdressers, painters, printers, aniline dye workers, machinists and truck drivers all have a greater risk because their work involves environmental factors that may cause cancer. Individuals who work with tobacco products or are exposed to large amounts of secondhand smoke are also at risk for bladder cancer.
- Race. Whites have double the risk of developing bladder cancer compared to Hispanics and African Americans. The lowest rate of bladder cancer is found among Asians.
- Chronic bladder infection. Conditions such as urinary infections, bladder stones and kidney stones have been linked to bladder cancer, although they do not cause the disease.
- History of bladder cancer. Individuals who have had bladder cancer in the past are more likely to develop another tumor. People with a family history of bladder cancer also have a greater risk of developing the disease.
- Levels of angiogenin. Some research studies have shown that individuals with an elevated level of the antibody angiogenin may have an increased risk of bladder cancer. Additional research is necessary in this area.
- Bladder birth defects. Sometimes the connection between the bladder and navel in the fetus does not disappear before birth as it should and can become cancerous. Cancer associated with birth defects of the bladder is very rare.
- Genetic mutations. Risk for bladder cancer may be increased in people with a genetic mutation associated with retinoblastoma, an eye cancer most commonly seen in infants and young children.
- Previous treatment. Certain drugs or radiation used to treat other forms of cancer can increase bladder cancer risk in some individuals.
- Arsenic. An increased risk of bladder cancer has been linked to arsenic in drinking water.
- Parasitic infections. Being infected with certain parasites can increase bladder cancer risk. These parasites are not typically found in the United States.
- Hormones. Studies have indicated that hormonal factors may affect a woman’s chance of developing the disease. Women who enter menopause at an earlier age may have a higher risk of bladder cancer. Researchers speculate that lower estrogen levels may increase bladder dysfunction and be associated with frequent urinary tract infections, which are risk factors for the disease.
Certain other theories about bladder cancer risks have not been proven. For example, several artificial sweeteners have been associated with bladder cancer in laboratory animals when given in high doses, but the link in human cancer has not been established. Another piece of conventional wisdom has associated chlorinated water or chlorine by-products with bladder cancer. Researchers continue to study this issue, but no firm link has been established.
Signs and symptoms of bladder cancer
The first warning sign of bladder cancer is normally blood in the patient’s urine (hematuria). The blood may appear on a urine test, or the patient may notice that the urine is darker or more reddish in color than usual. Other common signs and symptoms of bladder cancer may include the following:
- Pelvic pain
- Pain in the abdomen or lower back
- Painful urination
- Changes in bladder habits
- Having to urinate more frequently
- Inability to urinate
Individuals who experience any of these signs or symptoms should notify their physician. Although these signs and symptoms may indicate bladder cancer, the most common causes of bladder symptoms are other medical conditions such as infections.
Diagnosis methods for bladder cancer
Physicians do not normally screen patients for bladder cancer and no professional organization recommends that the practice become standard. However, individuals previously diagnosed with bladder cancer and those with risk factors for the condition may benefit from a routine urinalysis, which can detect signs of bladder cancer, such as blood in the urine.
Individuals who suspect they may have bladder cancer, or those who experience any of the signs and symptoms of the condition, should notify their physician. Early detection and treatment of bladder cancer increases a patient’s chance for survival. Diagnosis of this condition typically begins with a complete medical history and a thorough physical examination, which may include an examination of the rectum and of the vagina (in female patients). This examination may help detect the presence and size of a tumor.
The physician may also recommend the following diagnostic tests:
- Cystoscopy. A test in which a cystoscope (a thin tube with a light and a lens) is inserted into the bladder via the urethra, allowing the physician to view the inside of the bladder. If suspicious tissue is detected, a sample is removed in a biopsy and is examined by a pathologist.
- Urine cytology. A test in which urine or cells flushed from the bladder are sent to a laboratory to determine if precancer or cancer cells are present.
- Urine culture. A sample of the patient’s urine is sent to a laboratory and analyzed for infection. Symptoms of bladder infection are often similar to those that accompany bladder cancer.
- Bladder tumor marker studies. Urine tests that identify certain substances that are released into the urine by cancer cells. Although some physicians use these tests, most believe that more research is needed to determine their efficacy.
A number of imaging tests may also be performed to allow the physician to view the kidney, bladder and other organs. These tests can include CT scans, MRI scans, ultrasound, x-rays and bone scans. The tests may provide the physician with additional information about the cancer, such as whether or not it has spread to other organs in the body.
In addition, an intravenous pyelogram may be ordered by the physician. This special x-ray test uses dye to examine the kidneys and ureters, the tubes that drain urine from the kidneys into the bladder.
After the diagnostic tests are performed, the physician will begin the process of staging, or determining the spread of the bladder cancer. Staging any type of cancer is very important because the stage of the cancer determines both the course of treatment and the outlook for recovery.
Treatment and prevention for bladder cancer
There is no definitive method to prevent bladder cancer at this time. However, individuals can lower their risk by quitting smoking and avoiding occupational exposure to chemicals believed to increase bladder cancer risk. In addition, the risk may be reduced by drinking large amounts of liquids and eating a diet rich in fruits and vegetables, especially cruciferous vegetables such as broccoli and cauliflower. In studies reported by the National Cancer Institute (NCI), a high intake of dietary carotenoids (foods rich in beta carotene) and dark green vegetables has been associated with an overall decreased risk for bladder cancer.
Treatment options for bladder cancer vary depending on the patient and the stage of cancer. In general, treatment will involve surgery. There are a number of different surgeries for bladder cancer. Some involve the removal of the entire bladder but others do not. The type of surgery typically depends on the stage of the bladder cancer.
Transurethral surgery is typically used to treat early stage bladder cancer. In this procedure, the surgeon removes the cancer with the aid of a cystoscope (a thin tube with a light and a lens), which is inserted into the bladder through the urethra. A cytoscope may also be used to burn away a portion of the tumor.
The patient will be given medicine to numb the area or has general anesthesia for the surgery. This procedure eliminates the need to cut into the abdomen. Side effects of transurethralsurgery are typically mild and may include some bleeding or light pain immediately after surgery. Patients are often discharged the same or following day, and can typically resume normal activities in less than two weeks. After transurethralsurgery, other steps may be necessary to eliminate any remaining cancer, such as laser treatment. Some urologists have advocated preservation of the bladder by using a combination of transurethral surgery, radiation therapy and chemotherapy.
When bladder cancer becomes invasive or has begun to spread to nearby tissues, some form of open surgery may be needed, either partial cystectomy,where part of the bladder is removed, or radical cystectomy, which removes the entire bladder as well as neighboring lymph nodes. In men, the prostate is typically removed during a radical cystectomy. In women, the uterus, ovaries, fallopian tubes and a small section of the vagina may be removed. Patients are asleep for both a partial and a radical cystectomy, and both surgeries require 7 to 10 days of hospitalization. Cystectomies have a recuperation period of four to six weeks.
Radical cystectomies can have serious side effects such as excess bleeding, infection, urine leakage and blockage of urine flow. Following a radical cystectomy, the body needs another method of storing and removing urine. Options include:
- Urostomy. A procedure in which tissue is moved from the small intestine and attached to the ureters, and a bag is worn outside the body to catch urine.
- Continent diversion. A procedure in which the surgeon attaches a sac (created from a small piece of the patient’s intestine) to the ureters. The patient then uses a drainage tube to empty urine. Unlike urostomy, there is no need to wear a urine collection bag outside of the body.
Other cancer therapies may also be used, either in addition to surgery or instead of surgery. These include:
- Radiation therapy. This treatment uses high-energy x-rays to shrink or eliminate cancer cells. The radiation may come from outside sources or radioactive materials placed directly inside the tumor. After surgery, radiation can often destroy tiny deposits of cancer cells that are too small to detect. Following transurethral surgery, a combination of radiation therapy and chemotherapycan sometimes eliminate cancer cells that would typically require a cystectomy.
- Intravesical immunotherapy. This type of immunotherapy is used to treat bladder cancers that are noninvasive or minimally invasive. Intravesical means that the treatment is placed directly inside the bladder instead of being administered orally or injected into the vein. Immunotherapy is the most common form of intravesical treatment for bladder cancer. It causes the body’s immune system to attack the tumor. The Bacillus Calmette Guerin (BCG) bacteria, which is used primarily to make a tuberculosis vaccine, is the immunotherapy most commonly used to treat bladder cancer.
- Chemotherapy. Often called “chemo,” this treatment uses drugs or combinations of drugs to kill cancer cells. These drugs are typically administered either intravenously or orally, although some forms may be placed intravesically into the patient’s bladder.
Follow-up care is also an essential part of any treatment plan. Patients typically receive follow-up examinations every three to six months after treatment to monitor whether the cancer has returned or if a new cancer has developed in the urinary system. Follow-up plans typically include a complete physical examination as well as tests such as blood tests and x-rays. Patients and families who have difficulty coping with bladder cancer may benefit from mental health counseling and support groups.
Ongoing research regarding bladder cancer
Great strides have been made in cancer research over the past 10 years. The following bladder cancer research is being conducted:
- Numerous changes in the DNA of bladder cancer have been identified in recent years. Researchers are now investigating whether the genetic tests that identify these DNA changes will be useful in predicting bladder cancers that return after treatment. Other studies are trying to determine whether these DNA tests can help predict the course of the cancer.
- Patients who have had bladder cancer in the past are more likely to develop a new cancer in another part of the urinary system. Researchers are currently studying certain vitamins and drugs that may help prevent new cancers from developing.
- The Food and Drug Administration (FDA) recently approved two new tumor marker tests for identifying bladder cancer that may have returned. Additional marker tests are currently being studied. In addition, a urine test that detects the presence of the enzyme telomerase is being evaluated for early detection of bladder cancer. In one study, the enzyme was found in 90 percent of men after that cancer was diagnosed by invasive examinations of the bladder and urinary tract.
- Photodynamic therapy (PDT) may be useful in treating the beginning stages of bladder cancer. PDT is a two step process. First, a chemical is injected into the bloodstream. A few days later, after the chemical has accumulated inside the tumor, a special laser light is focused on the cancer. The light alters the chemical, promoting the destruction of cancer cells. Although this treatment only works on cancers near the bladder’s surface, it does minimal harm to normal cells. PDT is not yet widely available.
- The FDA recently approved a new drug classified as an antitumor antibiotic to treat patients with very early stage bladder cancer. Additional drugs are currently being tested for treating individuals with advanced bladder cancer.
- Monoclonal antibodies that have been approved for colon cancer and kidney cancer therapy are being tested for bladder cancer. Some of these biological therapies work as angiogenesis inhibitors, blocking the blood supply of cancer cells.
- Researchers are currently testing the effects of gene therapy on bladder cancer. Changes in genes can promote abnormal growth of bladder cells. New designer viruses that contain a normal gene may help restore normal cell growth control to bladder cancer patients in the future.
- Numerous studies are also examining the timing of surgery as treatment for bladder cancer. Some studies have indicated the need for immediate surgery, while others have indicated that delaying surgery for several weeks will not adversely affect a patient’s prognosis. Additional research is needed to determine the correlation between treatment timing and progression of the cancer.
Staging bladder cancer
The prognosis (predicted outlook or chance of survival) of bladder cancer depends on the cancer’s “stage” and “grade.” The stage indicates the extent of the cancer, or how widespread it is in the body. The grade measures how abnormal the cells look under a microscope. The grading and staging systems are combined into another system that allows the physician to discuss the pathology of the tumor in lay terms. These stages include:
- Stage 0. The least serious stage in which bladder cancer is present, but has not invaded the bladder’s muscle or connective tissue, or spread to the lymph nodes or distant sites.
- Stage I. The cancer has grown into the lining of the urethra, bladder, ureters or kidneys but has not spread to other layers of the bladder wall.
- Stage II. The cancer has spread to the main muscle layer of the bladder but has not reached the layer of fatty tissue surrounding the bladder.
- Stage III. The cancer has spread through the bladder wall into the surrounding layer of fatty tissue. It may have invaded the prostate, vagina or uterus, but has not spread to the lymph nodes or distant sites.
- Stage IV. The most advanced stage in which the cancer has spread through the bladder wall to the abdominal or pelvic wall and/or has invaded the lymph nodes and/or distant sites including the bones, lungs or liver.
Physicians use a much more complicated system for staging bladder cancer that was developed by the American Joint Committee on Cancer (AJCC). This system is commonly known as the “TNM” system, where:
- “T” describes the extent of a tumor’s invasion into the wall of the bladder and nearby tissues. Sometimes additional letters will follow the T, such as “Tm,” which indicates the presence of multiple cancers, or “Tis,” which indicates that the cancer is superficial (carcinoma in situ) and has not invaded surrounding tissues.
- “N” describes whether or not the cancer has spread to surrounding lymph nodes and, if so, the size of the lymph nodes. Lymph nodes are groups of immune system cells that help ward off infections and cancers. They are typically the size of a bean.
- “M” describes whether or not the cancer has metastasizedor spread to distant organs, such as the lungs, or to lymph nodes that do not surround the bladder.
The following chart reflects the relative five-year survival rate of bladder cancer patients by stage. In this case, “relative” refers to deaths from bladder cancer, not from other causes. This distinction is important with bladder cancer because half of patients diagnosed are age 73 or older. It is also important to note that many patients live much longer than five years. Additionally, every patient’s situation is unique and statistics cannot predict the exact outcome of an individual case.
|Stage||Five-Year Survival Rate|
Questions for your doctor about bladder cancer
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their condition. Patients may wish to ask their doctor the following questions about bladder cancer:
- How will I know my symptoms are due to bladder cancer?
- What tests will be used to diagnose my cancer?
- What type of bladder cancer do I have?
- What is the stage and grade of my cancer?
- What are my treatment options?
- What are the risks associated with my treatment options?
- If I need surgery, what type of surgery will I have?
- What are the long-term effects of this type of surgery?
- What are the chances that my cancer will return?
- How will I be monitored after my treatment?
- Are there any steps I can take to prevent a recurrence?
- Are my children at higher risk for this cancer?