Bladder Cancer

Transitional cell carcinoma, also called urothelial carcinoma, is the most common type of bladder cancer.

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

• The bladder is connected to the kidneys by a tube from each kidney called a ureter.
• When the bladder reaches its capacity for 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 degenerative, dangerous, or what is called a malignant change or transformation causing them to grow abnormally and multiply without normal controls. A mass of cancerous cells is called a malignant tumor or cancer. The cancerous cells are capable of spreading to other areas of the body through the process of metastasis. Cancer can become destructive locally to the tissues adjacent to where it arises. Cancer cells can also metastasize. Metastasis means that cells spread through the tissue fluid's circulation called the lymphatic system or through the bloodstream where they can then stop off in other tissues or organs where they may grow as metastases or metastatic deposits and can become destructive in these new locations. The term cancer is further described by the tissue in which it has arisen. For example, bladder cancer is a different disease than lung cancer. If a bladder cancer cell metastasizes -- that is, spreads to the lungs through the bloodstream it is still called and is treated as metastatic bladder cancer, not as lung cancer.

Cells that transform in a less dangerous fashion may still multiply and form masses or tumors. These are called benign tumors. They do not metastasize.

Of the different types of cells that form the bladder, the cells lining the inside of the bladder wall are the 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, the urothelium. 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 are comprised of cells that typically form as a result of bladder inflammation or irritation that has taken place for many months or years. These cells grow in flat masses of interconnected cells.
• 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 kidney's internal collecting system, the ureters (narrow tubes that carry urine from the kidneys to the bladder), the bladder, and the urethra are lined with these cells. Thus, individuals with transitional cell cancers of the bladder are at risk for transitional cell cancers of the kidneys/ureter (upper urinary tract).

We do not know exactly what causes bladder cancer. Bladder cancer may develop related to changes in DNA (the material in cells that makes up genes and controls how cells work). These changes may turn on certain genes, oncogenes, that will tell the cells to grow, divide, and stay alive, or turn off suppressor genes, genes that control the division of cells, repair of mistakes in the DNA, and death of cells. Changes in genes may be inherited (passed on from parents) or acquired as a result of certain risk factors.

A number of chemicals (carcinogens) have been identified that are potential causes, especially in cigarette smoke. We do know that the following factors increase a person's risk of developing bladder cancer:

• Tobacco Smoking: Smoking is the single greatest risk factor for bladder cancer. Smokers are at least three times more likely to develop bladder cancer than nonsmokers. Smoking cessation is key to lessening the risk of relapse, especially in superficial bladder cancer.
• 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. Not drinking enough fluids, especially water, each day may increase the risk of bladder cancer. The data regarding the effects of coffee on the risk of developing bladder cancer are variable; however, currently, coffee consumption is actually thought to decrease the risk of several cancers.
• Medications: According to the U.S. Food and Drug Administration (FDA), the use of the diabetes medication pioglitazone (Actos) for more than one year may increase the risk of developing bladder cancer. Prior chemotherapy with the medication cyclophosphamide (Cytoxan) also can increase the risk of bladder cancer.
• Pelvic radiation for cancers of the pelvic organs (prostate, uterus, cervix, and colon/rectum) may increase the risk of bladder cancer.
• Arsenic in the drinking water, although not typically a problem in the United States, may also increase the 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, chronic indwelling urinary catheters (Foley catheters), and other urinary tract problems that irritate the bladder increase the risk of developing cancer, more commonly squamous cell carcinoma.
• Infection with a parasite (a worm), schistosomiasis, can increase the risk of bladder cancer. Schistosomiasis is common in Egypt and also noted in Africa and the Middle East.
• Birth defects: The urachus is a connection between the belly button (umbilicus) and the bladder in the fetus that typically disappears before birth, but if part of the connection remains after birth, it can become cancerous with a type of cancer called a urachal adenocarcinoma. A rare birth defect, bladder exstrophy, in which the bladder and belly wall is open and the bladder is exposed outside of the body, can increase the risk of bladder cancer.
• Genetics and family history: Those individuals with family members with bladder cancer are at increased risk of developing bladder cancer. Several genetic syndromes are associated with an increased risk of developing bladder cancer, including defects in the retinoblastoma (RB1) gene, Cowden disease, and Lynch syndrome.

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, having trouble urinating, or having a weak urine stream

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 healthcare professional right away. People who can see blood in their urine (gross hematuria), 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; however, it is also associated with a number of benign medical problems such as urinary tract infections, kidney/bladder stones, and benign tumors, and does not mean a person has 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, gross hematuria. 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 beyond just being more or less concentrated, particularly if you see blood in the urine, you need to see your healthcare professional promptly. Visible blood in the urine is referred to as gross, or macroscopic, hematuria.

Bladder cancer often causes no symptoms until it reaches an advanced stage that is difficult to cure. Therefore, you may want to talk to your healthcare professional 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.

• Any new changes in urinary habits or appearance of the urine warrant a visit to your healthcare professional, 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.

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 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 healthcare professional right away for evaluation.
• If you have risk factors, talk to your health-care professional 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, history, physical examination, urinalysis, urine cytology, and cystoscopy.
• Medical interview: Your health-care professional 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 professional 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. Blood in the urine, hematuria, although more commonly associated with noncancerous (benign) conditions, may be associated with bladder cancer and thus deserves further evaluation.
• 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.
• Fluorescence cystoscopy (blue light cystoscopy) is a special type of cystoscopy involving the placement of a light-activated drug into the bladder, which is picked up by the cancer cells. The cancer cells are identified by shining a blue light through the cystoscope and looking for fluorescent cells (the cells that have picked up the drug).

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.
• Retrograde pyelogram: This study involves injecting dye into the ureter, the tube that connects the kidney to the bladder, to fill the ureter and inside of the kidney. The dye is injected by placing a small hollow tube through the cystoscope and inserting the hollow tube into the opening of the ureter in the bladder. X-ray pictures are taken during the filling of the ureter and kidney to look for areas that don't fill out with the dye, known as filling defects, which could be tumors involving the ureter and/or lining of the kidney. This test may be performed to evaluate the kidneys and ureters in individuals who are allergic to the intravenous dye and thus cannot have a CT scan with contrast (dye) performed.
• MRI (magnetic resonance imaging) is also an alternative test to look at the kidneys, ureters, and bladder in individuals with contrast (dye) allergies.
• 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. (transurethral resection of bladder tumor [TURBT]).
• 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.
• Urine tumor markers: There are several newer molecular tests that look at substances in the urine that might help determine if bladder cancer is present. These include UroVysion (FISH), BTA tests, ImmunoCyt, NMP 22 BladderChek, and BladderCx.

If a tumor is found in the bladder, other tests may be performed, either at the time of diagnosis or later, to determine whether 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. PET/CT, a special type of CT scan, may be helpful in the evaluation of individuals with invasive, higher-stage bladder cancer to determine if the bladder cancer has spread.
• MRI (magnetic resonance imaging) may also be useful in the staging of bladder cancer and can be performed without contrast in individuals with a contraindication to contrast.
• 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 cancer may have affected the bones.

Bladder Cancer Staging

Cancer is described to its extent, or staged, using a system developed by consensus among cancer specialists.

Staging describes the extent of cancer when it is first found or diagnosed. This includes the depth of invasion of bladder cancer, and whether or not the cancer is still only in the bladder, or has already spread to tissues beyond the bladder including lymph nodes, or has spread or metastasized to distant organs.

Bladder cancers are classified by how deeply they invade into the bladder wall, which has several layers. Typically we subdivide bladder cancer into superficial and invasive diseases.

• 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 how deeply cancer penetrates 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 high-grade cancer have more changes in form and have a greater degree of abnormality when viewed microscopically than do cells from low-grade tumors. This information is provided by the pathologist, a physician trained in the science of tissue analysis and diagnosis.

• Low-grade tumors are usually less aggressive.
• High-grade tumors are more dangerous and have the propensity to become invasive even if they are not invasive when first found.
• Papillary tumors are urothelial carcinomas that grow in narrow, finger-like projections.
• Benign (noncancerous) papillary tumors (papillomas) grow as 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 invasive and become malignant. A small percentage (about 15%) do invade the bladder wall. Some invasive papillary tumors grow as 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 often high-grade and have a high risk of becoming invasive.

Of all types of cancer, bladder cancer has an unusually high propensity for recurring after initial treatment if that treatment was only a local removal or excision typically by transurethral resection. Bladder cancer treated in that fashion 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 another part of the urinary tract (kidneys or ureters).

Who is at risk of bladder cancer?

Bladder cancer is most common in industrialized countries. It is the fifth most common type of cancer in the United States. It is 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 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 among the most expensive cancers to treat on a per-patient basis.

As in most cancers, the chances of recovery are determined by the stage of the disease. Stage refers to the size of 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 ultrasounds) and biopsy results. Each stage has its own treatment options and a chance for cure. In addition, equally important is the grade of 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 and is considered noninvasive
• 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, into the muscularis propria. It may be into the first half, superficial, or the outer half of the bladder wall, deep.
• Stage T3: Cancer that has invaded all the way through the thickness of the muscular bladder wall and into surrounding fat. If the extension is only seen under the microscope, it is pT3b, and if a mass is seen outside of the bladder wall, it is called pT3b.
• Stage T4: Cancer that has invaded adjacent structures, such as the prostate, uterus, seminal vesicles, pelvic wall, abdominal wall, or vagina but not to lymph nodes in the region
• Staging also includes N and M classifications to define when cancer has spread to lymph nodes (N) or to distant organs such as the liver, lungs, or bones (M).
  • N0: no lymph node metastases
  • N1: single local lymph node metastasis in the pelvis
  • N2: lymph node metastases to local areas in the pelvis
  • N3: lymph nodes metastases to areas further away in the pelvis, the common iliac nodes
  • M0: no distant metastases
  • M1: distant metastases

The life expectancy for people with bladder cancer varies dramatically depending on the stage of cancer at the time of diagnosis.

• Nearly 90% of people treated for superficial bladder cancer (Ta, T1, CIS) survive for at least five years after treatment.
• The average survival time for patients with metastatic bladder cancer spread to other organs is 12 to 18 months. Some live longer than that, and some less time than that. Historically it has been noted that most patients that respond to treatment live longer than those who do not.
• Recurrent cancer indicates a more aggressive type and a poor outlook for long-term survival for patients with advanced-stage bladder cancer. Recurrent low-grade superficial bladder cancer is rarely life-threatening unless it is neglected such as if a patient does not bring recurrent symptoms or problems to the doctor's attention and it becomes invasive bladder cancer.

Although medical treatments are fairly standardized, different doctors have different philosophies and practices in caring for their patients. If bladder cancer is suspected or is a possible concern of your primary care doctor or internists then they may refer you to a urologist. Urologists are surgeons who specialize in the management of disorders of the urinary system. When selecting your urologist, you will want to identify someone skilled in treating bladder cancer and with whom you feel comfortable.

• 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.
• A urologist may also recommend or involve other specialists in your care either for their opinions or assistance in treating you. These specialists may be radiation oncologists and/or medical oncologists.
• Talk to family members, friends, and your healthcare 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 cancer before are included in the treatment decision-making process.
• The decision of which treatment to pursue is made after discussions 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.

Other physicians that you may meet include a medical oncologist, a medical doctor specializing in the treatment of cancer, and a radiation oncologist, a specialized cancer doctor who treats cancer with radiation-based treatments.

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

• The type of therapy you receive will vary with the stage and grade of the bladder cancer and your overall health.
• For lower-grade and stage tumors, less invasive options such as treatments placed directly into the bladder referred to as intravesical therapy may be an option.
• For more invasive cancers, surgical therapies, radiation, and chemotherapy are options, depending on the extent of cancer and your overall health

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

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

• Surgery and radiation therapy are comparatively local therapies. This means that they get rid of cancer cells only in the treated area. The bladder itself may be treated or the surgery and/or radiation may be extended to adjacent structures in the pelvic region.
• Chemotherapy is a systemic therapy. This means that it can kill cancer cells almost anywhere in the body.
• Immunotherapy is also local therapy and involves a treatment placed into the bladder.

Radiation Therapy

Radiation is a painless, invisible high-energy ray that can kill both cancer cells and normal cells in its path. New radiation treatments can focus radiation better and damage fewer normal cells. Radiation may be given for small muscle-invasive bladder cancers. It is commonly used as an alternative approach to or in addition to surgery, often in patients who may be too ill to undergo surgery. Either of two types of radiation can be used. However, for the 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 into short treatments given five days a week for 5 to 7 weeks. Spreading it out this way helps protect the surrounding healthy tissues by lowering the dose of each treatment. In addition, as cells are more sensitive to radiation during different phases in cell growth, and cancer cells are typically faster growing than normal cells, the use of frequent dosing is designed to kill cancer cells more readily and decrease the risk of killing normal cells. 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 many different techniques. One involves 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 if the radiation cannot be focused enough. 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 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 the 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, and rectal irritation leading to changes in bowel movements, and blood in the stool as well as urinary problems, and sexual problems such as vaginal dryness in women and impotence in men. Such problems arise shortly after treatment begins, or may appear sometime after radiation treatments are completed.

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 a doctor's office or outpatient treatment clinic, but it may require a stay in the hospital

• Stages T_a, T₁, and CIS bladder cancer can be treated with intravesical chemotherapy, which means the placement of treatments directly into the bladder. After the 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 is often performed after the initial surgery to diagnose and remove, if possible, the bladder cancer to help kill any cancer cells that may be floating in the bladder after the surgery. Depending on the surgical findings and pathology, this treatment may be 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, can kill cancer cells wherever they are.

Chemotherapy's side effects depend on which drugs you receive and how the drugs are given. Newer drugs to control some of these effects have been developed. Systemic chemotherapy is usually prescribed and overseen by a specialist called a medical oncologist.

• 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). Numbness or tingling in the hands or feet can occur. 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, 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 called antibodies and recruits and directs specific cells called types of lymphocytes which can be found both in the blood and can move into the tissues to work against "invaders," such as abnormal cells (that is, cancer cells).
• Sometimes, the immune system becomes overwhelmed by very aggressive cancer cells.
• Biological therapy, or immunotherapy, helps bolster the immune system in its fight against 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, or weakened cow TB (tuberculosis) bacteria (containing 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 and then can be safely urinated out in the toilet, flushing and cleaning the toilet with bleach after. This treatment is repeated every week for 6 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 the stimulation of the immune system. These effects are almost always temporary.
• Rarely, the use of intravesical BCG can be associated with an infection from the bacteria, and this may affect the prostate or may spread to other areas of the blood via the bloodstream. If you have a high fever after BCG treatment and/or persistent fevers, you should notify your physician.

Surgery is by far the most widely used treatment for bladder cancer. It is used for all types and stages of bladder cancer. Several different types of surgery are used. Which type is used in any situation depends largely on the stage of the tumor. Many surgical procedures are available today that have not gained widespread acceptance. They can be difficult to perform, and good outcomes are best achieved by those who perform many of these surgeries per year. The types of surgery are as follows:

• Transurethral resection with fulguration: In this operation, an instrument (resectoscope) is inserted through the urethra and into the bladder. A small wire loop on the end of the instrument then removes the tumor by cutting it or burning it with an electrical current (fulguration). This is usually performed for the initial diagnosis of bladder cancer and for the treatment of stages Ta and T1 cancers. Your surgeon may administer a dose of intravesical mitomycin after the TURBT to prevent cancer cells that are floating in the bladder after the resection from attaching to the bladder and causing a recurrence of the bladder cancer. Often, after transurethral resection, additional treatment is given (for example, intravesical therapy) to help treat the bladder cancer, depending on the grade and stage of the bladder cancer.
• Radical cystectomy: In this operation, the entire bladder is removed, as well as its surrounding lymph nodes and other structures adjacent to the bladder that may contain cancer. This is usually performed for cancers that have at least invaded the muscular layer of the bladder wall or for more superficial cancers that extend over much of the bladder or that have failed to respond to more conservative treatments. Occasionally, the bladder is removed to relieve severe urinary symptoms.
• If the urethra, the tube that connects the bladder to the perineum, is involved with cancer, the urethra may need to be removed along with the bladder, known as radical cystectomy plus urethrectomy (cystourethrectomy).
• Segmental or partial cystectomy: In this operation, part of the bladder is removed. This is usually performed for solitary low-grade tumors that have invaded the bladder wall but are limited to a small area of the bladder and have not spread outside of the bladder.

As the name implies, radical cystectomy is major surgery. Not only the entire bladder but also other structures are removed.

• In men, the prostate and seminal vesicles are removed. (The seminal vesicles are small structures that contain fluid that is part of the ejaculate.) This operation stops prevents sperm and semen from coming out when you ejaculate, called dry ejaculate. The nerves that go to the penis to cause erections may also be affected by the surgery, causing erectile dysfunction.
• In women, the womb (uterus), ovaries, and part of the vagina are removed. This permanently stops menstruation, and you can no longer become pregnant. The operation may also interfere with sexual and urinary functions.
• Removal of the bladder is complicated because it requires the creation of a new pathway for urine to be stored and leave the body. There are a variety of different surgical procedures that can be performed. Some people wear a bag outside the body to collect urine, called non continent urinary diversion. Others have a small pouch made inside the body to collect urine, known as continent urinary diversion. The pouch is usually made by a surgeon from a small piece of the intestine. A connection between the pouch and the skin can be catheterized with a small catheter (hollow tube) to empty the pouch. In others, a new bladder can be made of the intestine that is sewn to the urethra (neobladder), and one can void either by increasing abdominal pressure or catheterizing per urethra to empty the bladder,
• Historically, the ureters, the tubes that drained the kidneys, were attached to the colon, and one would empty both urine and stool together. This procedure was associated with a risk of developing cancer near the area where the ureter was sewn into the colon, so it is rarely used today in the U.S. but may still be used in some underdeveloped countries.
• Surgeons and medical oncologists are working together to find ways to avoid radical cystectomy. A combination of chemotherapy and radiation therapy may allow some patients to preserve their bladder; however, the toxicity of the therapy is significant, with many patients requiring surgery to remove the bladder at a later date, due to severe voiding symptoms, frequency, urgency, pain and blood in the urine.

If your urologist recommends surgery as a treatment for your bladder cancer, be sure you understand the type of surgery you will have and what effects the surgery will have on your life.

Even if the surgeon believes that the entire cancer is removed by the operation, many people who undergo surgery for bladder cancer receive chemotherapy after the surgery. This "adjuvant" (or "in addition") chemotherapy is designed to kill any cancer cells remaining after surgery and to increase the chance of a cure.

Some patients may receive chemotherapy before radical cystectomy. This is called "neoadjuvant" chemotherapy and may be recommended by your surgeon and oncologist. Neoadjuvant chemotherapy can kill any microscopic cancer cells that may have spread to other parts of the body and can also shrink the tumor in your bladder before surgery.

• If it has been decided that you need chemotherapy in conjunction with your radical cystectomy, the decision to elect neoadjuvant before surgery or adjuvant chemotherapy after surgery will be made together on a case-by-case basis by the patient, medical oncologist, and urologic oncologist.

Bladder cancer has a relatively high recurrence rate. Researchers are trying to discover ways to prevent a recurrence. One strategy that has been widely tested is chemoprevention.

• The idea is to use an agent that is safe and has few, if any, side effects but is active in changing the environment of the bladder so another cancer cannot develop so easily there.
• The agents most widely tested as chemopreventives are vitamins and certain relatively safe drugs.
• No agent has yet been shown to work on a large scale in preventing the recurrence of bladder cancer.

Another treatment for bladder cancer that is still under study is called PDT, or photodynamic therapy. This treatment uses a special type of laser light to destroy tumors.

• For a few days before the treatment, you are given a substance that sensitizes tumor cells to this light. The substance is infused into your bloodstream via a vein. It then travels to the bladder and collects in the tumor.
• The light source is then introduced into the bladder through the urethra and light is then aimed at the tumor and can destroy tumor cells.
• The advantage of this treatment is that it kills only tumor cells, not surrounding healthy tissues. The disadvantage is that it works only for tumors that have not invaded deeply into the bladder wall or to other organs. This treatment is not readily available in most centers in the United States and is not widely used.

After you complete your treatment, you will undergo a series of tests to determine how well your treatment worked at getting rid of your cancer.

• If the results show remaining cancer, your urologic oncologist will recommend further treatment.
• If the results show no remaining cancer, he or she will recommend a schedule for follow-up visits. These visits will include tests to see whether cancer has come back. They will be frequent at first because of the risk of cancer recurrence after treatment.
• If you still have your native bladder, follow-up will include interval cystoscopy and urine tests.
• If you have undergone radical cystectomy, follow-up will include imaging tests of your chest and abdomen.

No sure way exists to prevent bladder cancer. You can reduce your risk factors, however.

• If you smoke, quit. However, the risk of bladder cancer does not diminish.
• Avoid unsafe exposures to chemicals in the workplace. If your work involves chemicals, make sure you are protected.

Drinking plenty of fluids may dilute any cancer-causing substances in the bladder and may help flush them out before they can cause damage.