bladder cancer treatment 2011-2012

Bladder Cancer Overview

The bladder is a hollow organ in the lower abdomen (pelvis). It collects and stores urine produced by the kidneys.

• As it fills with urine, the muscular wall of the bladder stretches and the bladder gets larger.
  
  
• When the bladder reaches its capacity of urine, the bladder wall contracts, although adults have voluntary control over the timing of this contraction. At the same time, a urinary control muscle (sphincter) in the urethra relaxes. The urine is then expelled from the bladder.
  
  
• The urine flows through a narrow tube called the urethra and leaves the body. This process is called urination, or micturition.

Cancer occurs when normal cells undergo a transformation whereby they grow and multiply without normal controls.

• As the cells multiply, they form an area of abnormal cells. Medical professionals call this a tumor.
  
  
• As more and more cells are produced, the tumor increases in size.
  
  
• Tumors overwhelm surrounding tissues by invading their space and taking the oxygen and nutrients they need to survive and function.
  
  
• Tumors are cancerous only if they are malignant. This means that, because of their uncontrolled growth, they encroach on and invade neighboring tissues.
  
  
• Malignant tumors may also travel to remote organs via the bloodstream or the lymphatic system.
  
  
• This process of invading and spreading to other organs is called metastasis. Bladder cancers are most likely to spread to neighboring organs and lymph nodes prior to spreading through the blood stream to the lungs, liver, bones, or other organs.

Of the different types of cells that form the bladder, the cells lining the inside of the bladder wall are most likely to develop cancer. Any of three different cell types can become cancerous. The resulting cancers are named after the cell types.

• Urothelial carcinoma (transitional cell carcinoma): This is by far the most common type of bladder cancer in the United States. The so-called transitional cells are normal cells that form the innermost lining of the bladder wall. In transitional cell carcinoma, these normal lining cells undergo changes that lead to the uncontrolled cell growth characteristic of cancer.
  
  
• Squamous cell carcinoma: These cancers originate from the thin, flat cells that typically form as a result of bladder inflammation or irritation that has taken place for many months or years.
  
  
• Adenocarcinoma: These cancers form from cells that make up glands. Glands are specialized structures that produce and release fluids such as mucus.
  
  
• In the United States, urothelial carcinomas account for more than 90% of all bladder cancers. Squamous cell carcinomas make up 3%-8%, and adenocarcinomas make up 1%-2%.

Only transitional cells normally line the rest of the urinary tract. The kidneys, the ureters (narrow tubes that carry urine from the kidneys to the bladder), the bladder, and the urethra are lined with these cells.

• However, these three types of cancer can develop anywhere in the urinary tract.
  
  
• If abnormal cells are found anywhere in the urinary tract, a search for other areas of abnormal cells is warranted. For example, if cancerous cells are found in the bladder, an evaluation of the kidneys and ureters is essential.

Bladder cancers are classified (staged) by how deeply they invade into the bladder wall, which has several layers. Many physicians subdivide bladder cancer into superficial and invasive disease. Superficial bladder cancer is limited to the innermost linings of the bladder (known as the mucosa and lamina propria). Invasive bladder cancer has at least penetrated the muscular layer of the bladder wall.

• Nearly all adenocarcinomas and squamous cell carcinomas are invasive. Thus, by the time these cancers are detected, they have usually already invaded the bladder wall.
  
  
• Many urothelial cell carcinomas are not invasive. This means that they go no deeper than the superficial layer (mucosa) of the bladder.

In addition to stage (how deep the cancer penetrates in the bladder wall), the grade of the bladder cancer provides important information and can help guide treatment. The tumor grade is based on the degree of abnormality observed in a microscopic evaluation of the tumor. Cells from a high-grade cancer have more changes in form and have a greater degree of abnormality when viewed microscopically than do cells from a low-grade tumor. This information is provided by the pathologist, a physician trained in the science of tissue diagnosis.

• Low-grade tumors are less aggressive.
  
  
• High-grade tumors are more dangerous and have a propensity to become invasive.

Papillary tumors are urothelial carcinomas that grow narrow, finger-like projections.

• Benign (noncancerous) papillary tumors (papillomas) grow projections out into the hollow part of the bladder. These can be easily removed, but they sometimes grow back.
  
  
• These tumors vary greatly in their potential to come back (recur). Some types rarely recur after treatment; other types are very likely to do so.
  
  
• Papillary tumors also vary greatly in their potential to be malignant (invasive). A small percentage (15%) do invade the bladder wall. Some invasive papillary tumors grow projections both into the bladder wall and into the hollow part of the bladder.

In addition to papillary tumors, bladder cancer can develop in the form of a flat, red (erythematous) patch on the mucosal surface. This is called carcinoma-in-situ (CIS).

• Although these tumors are superficial, they are high-grade and have a high risk for becoming invasive.

Of all types of cancer, bladder cancer has an unusually high propensity for recurring after treatment. Bladder cancer has a recurrence rate of 50%-80%. The recurring cancer is usually, but not always, of the same type as the first (primary) cancer. It may be in the bladder or in another part of the urinary tract (kidneys or ureters).

Bladder cancer is most common in industrialized countries. It is the fifth most common type of cancer in the United States-the fourth most common in men and the ninth in women.

• Each year, about 67,000 new cases of bladder cancer are expected, and about 13,000 people will die of the disease in the U.S.
  
  
• Bladder cancer affects three times as many men as women. Women, however, often have more advanced tumors than men at the time of diagnosis.
  
  
• Whites, both men and women, develop bladder cancers twice as often as other ethnic groups. In the United States, African Americans and Hispanics have similar rates of this cancer. Rates are lowest in Asians.
  
  
• Bladder cancer can occur at any age, but it is most common in people older than 50 years of age. The average age at the time of diagnosis is in the 60s. However, it clearly appears to be a disease of aging, with people in their 80s and 90s developing bladder cancer as well.
  
  
• Because of its high recurrence rate and the need for lifelong surveillance, bladder cancer is the most expensive cancer to treat on a per patient basis.

Bladder Cancer Causes

We do not know exactly what causes bladder cancer; however, a number of carcinogens have been identified that are potential causes, especially in cigarette smoke. Research is focusing on conditions that alter the genetic structure of cells, causing abnormal cell reproduction. We do know that the following factors increase a person's risk of developing a bladder cancer:

• Smoking: Smoking is the single greatest risk factor for bladder cancer. Smokers have more than twice the risk of developing bladder cancer as nonsmokers.
  
  
• Chemical exposures at work: People who regularly work with certain chemicals or in certain industries have a greater risk of bladder cancer than the general population. Organic chemicals called aromatic amines are particularly linked with bladder cancer. These chemicals are used in the dye industry. Other industries linked to bladder cancer include rubber and leather processing, textiles, hair coloring, paints, and printing. Strict workplace protections can prevent much of the exposure that is believed to cause cancer.
  
  
• Diet: People whose diets include large amounts of fried meats and animal fats are thought to be at higher risk of bladder cancer.
  
  
• Aristolochia fangchi: This herb is used in some dietary supplements and Chinese herbal remedies. People who took this herb as part of a weight loss program had higher rates of bladder cancer and kidney failure than the general population. Scientific studies on this herb have shown that it contains chemicals that can cause cancer in rats.

These are factors you can do something about. You can stop smoking, learn to avoid workplace chemical exposures, or change your diet. You cannot do anything about the following risk factors for bladder cancer:

• Age: Seniors are at the highest risk of developing bladder cancer.
  
  
• Sex: Men are three times more likely than women to have bladder cancer.
  
  
• Race: Whites have a much higher risk of developing bladder cancer than other races.
  
  
• History of bladder cancer: If you have had bladder cancer in the past, your risk of developing another bladder cancer is higher than if you had never had bladder cancer.
  
  
• Chronic bladder inflammation: Frequent bladder infections, bladder stones, and other urinary tract problems that irritate the bladder increase the risk of developing a cancer, more commonly squamous cell carcinoma.
  
  
• Birth defects: Some people are born with a visible or invisible defect that connects their bladder with another organ in the abdomen or leaves the bladder exposed to continual infection. This increases the bladder's vulnerability to cellular abnormalities that can lead to cancer.

Bladder Cancer Symptoms

The most common symptoms of bladder cancer include the following:

• Blood in the urine (hematuria)
  
  
• Pain or burning during urination without evidence of urinary tract infection
  
  
• Change in bladder habits, such as having to urinate more often or feeling the strong urge to urinate without producing much urine

These symptoms are nonspecific. This means that these symptoms are also linked with many other conditions that have nothing to do with cancer.

• Having these symptoms does not necessarily mean you have bladder cancer.
  
  
• If you have any of these symptoms, you should see your health-care provider right away. People who can see blood in their urine, especially older males who smoke, are considered to have a high likelihood of bladder cancer until proven otherwise.

Blood in the urine is usually the first warning sign of bladder cancer.

• Unfortunately, the blood is often invisible to the eye. This is called microscopic hematuria, and it is detectable with a simple urine test.
  
  
• In some cases, enough blood is in the urine to noticeably change the urine color. The urine may have a slightly pink or orange hue, or it may be bright red with or without clots.
  
  
• If your urine changes color, you need to see your health-care provider.

Bladder cancer often causes no symptoms until it reaches an advanced state that is difficult to cure. Therefore, you may want to talk to your health-care provider about screening tests if you have risk factors for bladder cancer. Screening is testing for cancer in people who have never had the disease and have no symptoms but who have one or more risk factors.

When to Seek Medical Care

Any changes in urinary habits or appearance of the urine warrants a visit to your health-care provider, especially if you have risk factors for bladder cancer. In most cases, bladder cancer is not the cause, but you will be evaluated for other conditions that can cause these symptoms, some of which can be serious.

Exams and Tests

Like all cancers, bladder cancer is most likely to be successfully treated if detected early, when it is small and has not invaded surrounding tissues. The following measures can increase the chance of finding a bladder cancer early:

• If you have no risk factors, pay special attention to urinary symptoms or changes in your urinary habits. If you notice symptoms that last more than a few days, see your health-care provider right away for evaluation.
  
  
• If you have risk factors, talk to your health-care provider about screening tests, even if you have no symptoms. These tests are not performed to diagnose cancer but to look for abnormalities that suggest an early cancer. If these tests find abnormalities, they should be followed by other, more specific tests for bladder cancer.
  
  
• Screening tests: Screening tests are usually performed periodically, for example, once a year or once every five years. The most widely used screening tests are medical interview, physical examination, urinalysis, urine cytology, and cystoscopy.
  
  
• Medical interview: Your health-care provider will ask you many questions about your medical condition (past and present), medications, work history, and habits and lifestyle. From this, he or she will develop an idea of your risk for bladder cancer.
  
  
• Physical examination: Your health-care provider may insert a gloved finger into your vagina, rectum, or both to feel for any lumps that might indicate a tumor or another cause of bleeding.
  
  
• Urinalysis: This test is actually a collection of tests for abnormalities in the urine such as blood, protein, and sugar (glucose). Any abnormal findings should be investigated with more definitive tests.
  
  
• Urine cytology: The cells that make up the inner bladder lining regularly slough off and are suspended in the urine and excreted from the body during urination. In this test, a sample of the urine is examined under a microscope to look for abnormal cells that might suggest cancer.
  
  
• Cystoscopy: This is a type of endoscopy. A very narrow tube with a light and a camera on the end (cystoscope) is used to examine the inside of the bladder to look for abnormalities such as tumors. The cystoscope is inserted into the bladder through the urethra. The camera transmits pictures to a video monitor, allowing direct viewing of the inside of the bladder wall.

These tests are also used to diagnose bladder cancers in people who are having symptoms. The following tests might be done if bladder cancer is suspected:

• CT scan: This is similar to an x-ray film but shows much greater detail. It gives a three-dimensional view of your bladder, the rest of your urinary tract (especially the kidneys), and your pelvis to look for masses and other abnormalities.
  
  
• Pyelography: This is a series of x-ray films of your urinary tract taken after your have had a special dye injected into a vein (intravenous pyelography [IVP]) or into your urethra (retrograde pyelography). The dye highlights the organs of your urinary tract and makes the recognition of certain abnormalities easier. However, CT scanning with three-dimensional reconstruction is replacing pyelography in many centers in the United States.
  
  
• Biopsy: Tiny samples of your bladder wall are removed, usually during cystoscopy. The samples are examined by a physician who specializes in diagnosing diseases by looking at tissues and cells (pathologist). Small tumors are sometimes completely removed during the biopsy process.
  
  
• Urine tests: Other urine tests may be performed to rule out conditions or to obtain specifics about urine abnormalities. For example, a urine culture may be done to rule out an infection. The presence of certain antibodies and other markers may indicate cancer. Some of these tests may be helpful in detecting recurrent cancer very early.

If a tumor is found in the bladder, other tests may be performed, either at the time of diagnosis or later, to determine whether the cancer has spread to other parts of the body.

• Ultrasound: This is similar to the technique used to look at a fetus in a pregnant woman's uterus. In this painless test, a handheld device run over the surface of the skin uses sound waves to examine the contours of the bladder and other structures in the pelvis. This can show the size of a tumor and may show if it has spread to other organs.
  
  
• Chest x-ray film: A simple x-ray film of the chest can sometimes show whether bladder cancer has spread to the lungs.
  
  
• CT scan: This technique is used to detect metastatic disease in the lungs, liver, abdomen, or pelvis, as well as to evaluate whether obstruction of the kidneys has occurred.
  
  
• Bone scan: This test involves having a tiny amount of a radioactive substance injected into your veins. A full body scan will show any areas where the cancer may have affected the bones.

Staging

As in most cancers, the chances of recovery are determined by the stage of the disease. Stage refers to the size of the cancer and the extent to which it has invaded the bladder wall and spread to other parts of the body. Staging is based on imaging studies (such as CT scans, x-rays, or ultrasound) and biopsy results. Each stage has its own treatment options and chance for cure. In addition, equally important is the grade of the bladder cancer. High-grade tumors are significantly more aggressive and life threatening than low-grade tumors.

• Stage CIS: Cancer that is flat and is limited to the innermost lining of the bladder; CIS is high grade
  
  
• Stage T_a: Cancer that is limited to the most superficial mucosal layer (innermost lining) of the bladder
  
  
• Stage T₁: Cancer that has penetrated beyond the mucosal layer into the submucosal tissue (lamina propria)
  
  
• Stage T₂: Cancer that has invaded part way through the thickness of the muscular bladder wall
  
  
• Stage T₃: Cancer that has invaded all the way through the thickness of the muscular bladder wall and into surrounding fat
  
  
• Stage T₄: Cancer that has invaded adjacent structures, such as the prostate, uterus, or vagina, but not to lymph nodes in the region
  
  
• Stage T_1-4N_1-2M_1-2: Cancer that has spread to the outer abdominal or pelvic wall, to lymph nodes, or to distant organs such as the liver, lungs, or bones

Bladder Cancer Treatment 2011

Although medical treatments are fairly standardized, different doctors have different philosophies and practices in caring for their patients.

• You may want to talk to more than one urologist to find the one with whom you feel most comfortable. Clinical experience in treating bladder cancer is of the utmost importance.
  
  
• Talk to family members, friends, and your health-care provider to get referrals. Many communities, medical societies, and cancer centers offer telephone or Internet referral services.

After you have chosen a urologist to treat your cancer, you will have ample opportunity to ask questions and discuss the treatments available to you.

• Your doctor will describe each type of treatment, give you the pros and cons, and make recommendations based on published treatment guidelines and his or her own experience.
  
  
• Treatment for bladder cancer depends on the type of cancer and its stage. Factors such as your age, your overall health, and whether you have already been treated for the cancer before are included in the treatment decision-making process.
  
  
• The decision of which treatment to pursue is made with your doctor (with input from other members of your care team) and your family members, but the decision is ultimately yours.
  
  
• Be certain you understand exactly what will be done and why, and what you can expect from your choices. With bladder cancer, understanding the side effects of treatment is especially important.

Like all cancers, bladder cancer is most likely to be cured if it is diagnosed early and treated promptly.

• The most widely used therapies are surgery, radiation therapy, and chemotherapy, either alone or in combination.
  
  
• Immunotherapy or biological therapy, which takes advantage of the body's innate cancer-fighting ability, is used in some cases, especially for patients with stages Ta, T1, and CIS.
  
  
• Your treatment plan will be individualized for your specific situation.

Your treatment team will also include one or more nurses, a dietitian, a social worker, and other professionals as needed.

Medical Treatment

Standard therapies for bladder cancer include surgery, radiation therapy, chemotherapy, and immunotherapy or biological therapy.

• Surgery and radiation therapy are local therapies. This means that they get rid of cancer cells only in the treated area.
  
  
• Chemotherapy is systemic therapy. This means that it can kill cancer cells almost anywhere in the body.
  
  
• For more information, see the Surgery section.

Radiation Therapy

Radiation is a high-energy ray that kills cancer cells and normal cells in its path. Radiation may be given for small muscle-invasive bladder cancers. It is commonly used as an alternative approach to surgery. Either of two types of radiation can be used. However, for greatest therapeutic efficacy, it should be given in conjunction with chemotherapy:

• External radiation is produced by a machine outside the body. The machine targets a concentrated beam of radiation directly at the tumor. This form of therapy is usually spread out in short treatments given five days a week for five to seven weeks. Spreading it out this way helps protect the surrounding healthy tissues by lowering the dose of each treatment. External radiation is given at the hospital or medical center. You come to the center each day as an outpatient to receive your radiation therapy.
  
  
• Internal radiation is given by placing a small pellet of radioactive material inside the bladder. The pellet can be inserted through the urethra or by making a tiny incision in the lower abdominal wall. You have to stay in the hospital during the entire treatment, which lasts several days. Visits by family and friends are restricted to protect them from the effects of radiation. When the treatment is done, the pellet is removed and you are allowed to go home. This form of radiation is rarely used for bladder cancer in the United States.

Unfortunately, radiation affects not only cancer cells but also any healthy tissues it touches. With external radiation, healthy tissue overlying or adjacent to the tumor can be damaged. The side effects of radiation depend on the dose and the area of the body where the radiation is targeted.

• The area of your skin where the radiation passes through may become reddened, sore, dry, or itchy. The effect is not unlike a sunburn. Although these effects can be severe, they are usually not permanent. The skin in this area may become permanently darker, however. Internal organs, bones, and other tissues can also be damaged. Internal radiation was developed to avoid these complications.
  
  
• You may feel very tired during radiation therapy.
  
  
• Radiation to the pelvis, as is needed for bladder cancer, can affect production of blood cells in the bone marrow. Common effects include extreme tiredness, increased susceptibility to infections, and easy bruising or bleeding.
  
  
• Radiation to the pelvis may also cause nausea, diarrhea, urinary problems, and sexual problems such as vaginal dryness in women and impotence in men.

Chemotherapy

Chemotherapy is the use of powerful drugs to kill cancer. In bladder cancer, chemotherapy may be given alone or with surgery or radiation therapy or both. It may be given before or after the other therapies. Chemotherapy can usually be given in the oncologist's office, but it may require a stay in the hospital.

• Stages Ta, T1, and CIS bladder cancer can be treated with intravesical chemotherapy. After removal of the tumor, one or more liquid drugs are introduced into the bladder via a thin, plastic tube called a catheter. The drugs remain in the bladder for several hours and are then drained out, commonly with urination. This treatment is typically repeated once a week for several weeks.
  
  
• Cancer that has invaded deeply into the bladder, lymph nodes, or other organs requires systemic or intravenous chemotherapy. The cancer-fighting drugs are injected into the bloodstream via a vein. This way, the drugs get into almost every part of the body and, ideally, kill cancer cells wherever they are.

Chemotherapy is well known for its unpleasant side effects. The side effects depend on which drugs you receive and how the drugs are given.

• The severity of side effects varies by person. For unknown reasons, some people tolerate chemotherapy much better than others.
  
  
• Some of the most common side effects of systemic chemotherapy include nausea and vomiting, loss of appetite, hair loss, sores on the inside of the mouth or in the digestive tract, feeling tired or lacking energy (because of anemia, that is, low red blood cell count), increased susceptibility to infection (because of low white blood cell count), and easy bruising or bleeding (because of low platelet count). Ask your oncologist about the specific effects you should expect.
  
  
• These side effects are almost always temporary and go away when chemotherapy is over.
  
  
• Multiple studies have demonstrated that intravesical chemotherapy is effective in decreasing the recurrence rate of superficial bladder cancers on a short-term basis.
  
  
• Intravesical chemotherapy, such as Mitomycin C, is often given as a single dose in the bladder immediately after the tumor has been removed with cystoscopy.
  
  
• Intravesical chemotherapy can irritate the bladder or kidneys.
  
  
• Intravesical chemotherapy is not effective against bladder cancer that has already penetrated into the muscular wall of the bladder or has spread to the lymph nodes or other organs.

Immunotherapy or Biological Therapy

Biological therapy takes advantage of the body's natural ability to fight cancer.

• Your immune system forms substances in the blood that work against "invaders," such as abnormal cells (that is, cancer cells).
  
  
• Sometimes, the immune system becomes overwhelmed by the very aggressive cancer cells.
  
  
• Biological therapy, or immunotherapy, helps bolster the immune system in its fight against the cancer.
  
  
• Biological therapy is typically given only in stages T_a, T₁, and CIS bladder cancers.
  
  
• One widely used immunotherapy or biological therapy in bladder cancer is intravesical BCG treatment.
  
  
• A fluid containing BCG, an attenuated vaccine (altered Mycobacterium), is introduced into the bladder through a thin catheter that has been passed through the urethra.
  
  
• The Mycobacterium in the fluid stimulates the immune system to produce cancer-fighting substances.
  
  
• The solution is held in the bladder for a few hours, then drained. This treatment is repeated every week for six weeks and repeated at various times over several months or even longer in some cases. Researchers are still working to determine the best length of time for these treatments. Over time, the treatments may be required on a less frequent basis.
  
  
• BCG may irritate the bladder and cause minor bleeding in the bladder. The bleeding is typically invisible in the urine. You may feel the need to urinate more often than usual or pain or burning when you urinate. Other side effects include nausea, low-grade fever, and chills. These are caused by stimulation of the immune system. These effects are almost always temporary.