The bladder is an expandable, hollow organ in the pelvis that stores urine (the body's liquid waste) before it leaves the body during urination. The urinary tract, made up of the kidneys, ureters, bladder, and urethra, is lined with a layer of transitional cells called the urothelium. This layer of cells is separated from the muscularis propria (bladder muscles) by the lamina propria (a thin, fibrous band).

Bladder cancer is a malignant (cancerous) tumor that begins in the bladder. Bladder cancer is described as either noninvasive or invasive. Noninvasive cancer does not go through the lamina propria, and invasive cancer goes through the lamina propria. Noninvasive cancer may also be called superficial cancer, although that term is being used less often because it may incorrectly imply that this type of cancer is not serious. Invasive cancer is subdivided into cancer that only grows into the lamina propria or cancer that grows into the muscle layer.

There are three main types of bladder cancer:

Transitional cell carcinoma (TCC). TCC accounts for about 90% of all bladder cancer and begins in the urothelium. TCC is described in terms of its subcategories.

Squamous cell carcinoma. This type accounts for about 4% of all bladder cancers and starts in squamous cells, which are thin, flat cells.

Adenocarcinoma. This type accounts for about 2% of all bladder cancers and begins in glandular cells.

All three types can metastasize (spread) beyond the bladder. If the tumor has spread into the surrounding organs (the uterus and vagina in women and the prostate in men), it is called locally advanced disease. The first area of spread outside of these organs is usually the lymph nodes in the pelvis that drain the bladder. If it has spread into the liver, bones, lungs, or other parts of the body, these are distant metastases and the cancer may be called advanced disease.

There are other, less common types of cancer that arise in the bladder, including sarcoma (that begins in the muscle layers of the bladder) and small cell anaplastic cancer (a rare type of bladder cancer that is likely to spread to other parts of the body).

To learn about the cancer terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Basic Oncology Terms.

Statistics

In 2008, an estimated 68,810 adults (51,230 men and 17,580 women) will be diagnosed with bladder cancer in the United States. It is estimated that 14,100 deaths (9,950 men and 4,150 women) from this disease will occur this year. Bladder cancer is the fourth most common cancer among men, and the eighth most common cause of cancer death among men.

For noninvasive/superficial TCC, the five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) for people with bladder cancer is 92%. Seventy-five percent (75%) of bladder cancer is diagnosed at this stage. For patients with regional (pelvic lymph node) or distant metastasis, the survival rates are about 45% and 6%, respectively.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with bladder cancer. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

Statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2008.

A risk factor is anything that increases a person's chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop the disease, while others with no known risk factors do. Knowing your risk factors and communicating with your doctor can help guide you in making wise lifestyle and health-care choices.

The following factors can raise a person's risk of developing bladder cancer:

Smoking. The most common risk factor is cigarette smoking. Smokers are four to seven times more likely to develop bladder cancer than nonsmokers.

Age. The incidence of bladder cancer increases with age.

Gender. Men are three to four times as likely to develop bladder cancer than women, but women are more likely to die from bladder cancer than men. Before smoking rates for women increased to approach smoking rates for men, men were five to six times more likely to develop bladder cancer.

Race. White people are more than twice as likely to be diagnosed with bladder cancer than black people, but black people are twice as likely to die from the disease.

Chemicals. Chemicals used in textile, rubber, leather, dye, paint or print industries, some naturally occuring chemicals, and chemicals called aromatic amines can increase the risk of bladder cancer.

Chronic bladder problems. Bladder stones and infections may increase the risk of bladder cancer. Bladder cancer may occur more commonly in paraplegics (people who are paralyzed from the waist down) who have had repeated urinary infections.

Cyclophosphamide (Cytoxan) exposure. People who have taken the chemotherapy drug cyclophosphamide are at higher risk for developing bladder cancer.

Personal history. People who have already had bladder cancer are more likely to develop bladder cancer again.

Fluid intake. People who do not drink enough liquids on a regular basis may have a higher risk of bladder cancer.

Schistosomiasis. People who have some forms of this parasitic disease (found particularly in some areas of Africa and in the Mediterranean region of the world) are more likely to develop bladder cancer.

People with bladder cancer may experience the following symptoms. Sometimes, people with bladder cancer do not show any of these symptoms. Bladder cancer usually does not cause symptoms that specifically indicate cancer. Most bladder cancers are diagnosed when a person tells his or her doctor about hematuria (blood in the urine). General urine tests are not used to make a specific diagnosis of bladder cancer, because hematuria can signal other conditions besides bladder cancer, such as an infection or kidney stones. One type of urine test can indicate the presence of cancer is cytology, a test in which the urine is studied under the microscope to see if there are cancer cells (see Diagnosis).

If you are concerned about a symptom on this list, please talk with your doctor.

• Hematuria



• Pain during urination



• Frequent urination



• Feeling the need to urinate throughout the night



• Feeling the need to urinate, but not being able to pass urine

Symptoms of advanced bladder cancer may include pain, a change in bowel habits, unexplained loss of appetite, and weight loss.

Sometimes when the first symptoms of bladder cancer appear, the cancer has already metastasized to another part of the body. In this situation, the symptoms depend on the site of metastasis. For example, lung metastases may cause cough or shortness of breath, liver metastases may cause abdominal pain or jaundice (yellowing of the skin and whites of the eyes), and bone metastases may cause bone pain or fractures.

Doctors use many tests to diagnose cancer and determine if it has metastasized. Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
• The type of cancer
• Severity of symptoms
• Previous test results

The earlier bladder cancer is found, the better the chances for successful treatment. However, there is not yet a test that is accurate enough to screen the general population for bladder cancer, so most bladder cancer is diagnosed in people once they have symptoms. As a result, some patients have more advanced disease when the cancer is first identified, although more than 70% of new cases are still noninvasive.

The following tests may be used to diagnose bladder cancer:

Physical examination. A doctor can sometimes detect lumps in the wall of the bladder by examining the rectum and the pelvis. Metastases may also be detectable during a physical examination.

Cystoscopy and biopsy. The doctor places a cystoscope (a small, hollow viewing tube) through the urethra (urinary opening) to look into the bladder. If he or she sees abnormal tissue, he or she will do a biopsy, which involves removing a small piece of tissue and examining it under a microscope for cancer. A biopsy is the only definite way to diagnose bladder cancer and to tell which type it is.

Urine tests. The doctor tests a urine sample to determine if it contains tumor cells. If a patient is undergoing a cystoscopy (see above), an additional test may be performed that involves rinsing the bladder and collecting the liquid through the cystoscope or through another small tube that is inserted into the urethra. The urine specimen can be tested in a variety of ways. The most common way is to look at the cells in the specimen under a microscope; this is called urinary cytology. Voided urine (urine passed out of the body during normal urination) can also be examined by cytology. There are a variety of other urine cancer tests that involve molecular analysis and can be done with or instead of urinary cytology.

Intravenous pyelogram (IVP). A dye containing iodine is injected into the patient's bloodstream and filtered through the kidneys. The dye enters the urine. This helps the bladder to appear more clearly on an x-ray and can provide an outline of a tumor in the bladder wall.

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a patient's vein and is then carried by the blood and filtered by the kidneys, providing better detail on the image.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Newly Diagnosed.

To learn more about what to expect during common diagnostic tests, read Cancer.Net: Tests and Procedures.

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

One tool that doctors use to describe the stage is the TNM system. This system uses three criteria to judge the stage of the cancer: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to other parts of the body. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

• How large is the primary tumor and where is it located? (Tumor, T)



• Has the tumor spread to the lymph nodes? (Node, N)



• Has the cancer metastasized to other parts of the body? (Metastasis, M)

Tumor. Using the TNM system, the "T" plus a letter and/or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that describe more details about a patient's condition. This helps the doctor develop the best treatment plan for each patient. If there is more than one tumor, the lowercase letter "m" (multiple) is added to the "T" stage category. Tumor stage information is listed below.

TX: The primary tumor cannot be evaluated due to a lack of information.

T0: There is no evidence of a primary tumor in the bladder.

Ta: This refers to noninvasive papillary carcinoma. Cancer cells are grouped together and can typically be easily removed.

Tis: This stage involves carcinoma (cancer) in situ, or "flat tumor." This means that the cancer is only found in cells within the lining of the bladder. The doctor may also call it noninvasive/superficial bladder cancer or noninvasive flat carcinoma (the cancer is on or near the surface of the bladder). This type of bladder cancer often comes back after treatment, usually as another noninvasive cancer in the bladder.

T1: The tumor has invaded subepithelial connective tissue (the tissue below the membrane or covering of the bladder).

T2: The tumor has invaded the muscle.

T2a: The tumor has invaded the inner half of the muscle (which may be called the superficial muscle.)

T2b: The tumor has invaded the deep muscle of the bladder (the outer half of the muscle).

T3: The tumor has grown into the perivesical tissue (the fatty tissue that surrounds the bladder).

T3a: The tumor has grown into the perivesical tissue, as seen microscopically (through a microscope).

T3b: The tumor has grown into the perivesical tissue macroscopically. In other words, the tumor deposits are large enough to be seen during imaging tests or to be seen or felt by the doctor.

T4: The tumor has invaded any of the following: the abdominal wall, the pelvic wall, a man's prostate, or a woman's uterus or vagina.

T4a: The tumor has invaded the prostate, uterus, or vagina.

T4b: The tumor has invaded the pelvic wall or the abdominal wall.

Node. The "N" in the TNM staging system stands for lymph nodes, the tiny, bean-shaped organs that help fight infection. Lymph nodes near the bladder, within the true pelvis (called hypogastric, obturator, iliac, perivesical, pelvic, sacral, and presacral nodes), are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: The regional lymph nodes cannot be assessed due to a lack of information.

N0: No regional lymph node metastasis exists (meaning the cancer has not spread into the regional lymph nodes).

N1: There is metastasis in a single lymph node, with the size of its largest area being 2 centimeters (cm) or smaller.

N2: There is metastasis in a single lymph node, with a size greater than 2 cm but no more than 5 cm in its largest area. Or, the cancer has spread into more than one lymph node, with the size of each metastasis being 5 cm or smaller at its largest point.

N3: There is metastasis in at least one lymph node that measures more than 5 cm at its largest point.

Distant metastasis. The "M" in the TNM system indicates whether the cancer has spread to other parts of the body (to areas such as the lungs or the bones).

MX: Distant metastasis cannot be evaluated.

M0: The disease has not metastasized.

M1: There is distant metastasis.

Tumor grade. Doctors use the term grade to describe how much the tumor tissue appears like normal bladder tissue. A microscope is used to look at cells from the biopsy. The grade of a cancer can give the doctor an idea of how quickly the cancer may grow and spread. Normal bladder tissue usually has differentiated tissue (different types of cells grouped together). Cancerous bladder tissue is made up of cells that look more alike each other; this less differentiated tissue has fewer features of normal bladder tissue. Less differentiated cells tend to be more widely diffused (spread) and look like sheets of irregular cells without specific features of normal tissue. In general, the more differentiated the bladder tissue, the better the prognosis.

GX: The tumor grade cannot be identified.

G1: The cells look more like normal bladder tissue cells (well differentiated).

G2: The cells are somewhat different (moderately differentiated).

G3 The cells look unlike normal bladder tissue cells (poorly differentiated)

G4: The tumor cells do not resemble normal cells at all (undifferentiated).

Cancer stage grouping

Doctors assign the stage of the bladder cancer by combining the T, N, and M classifications.

Stage 0a: This is an early cancer that is only found on the surface of the inner (inside) lining of the bladder. Cancer cells are grouped together and can typically be easily removed. The cancer has not invaded the muscle or connective tissue of the bladder wall. This type of bladder cancer is also called noninvasive papillary transitional cell carcinoma (TCC).

Stage 0is: This stage of cancer, also known as flat or carcinoma in situ, is found only on the inner lining of the bladder. It has not grown inward toward the hollow part of the bladder, and it has not spread to the thick layer of muscle or connective tissue of the bladder. This is always a high-grade cancer (see above).

Larger image

Stage I: The cancer has grown through the inner lining of the bladder to the connective tissue layer (called the lamina propria). It has not spread to the thick layer of muscle in the bladder wall. It has not spread to the lymph nodes or any other organs.

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Stage II: The cancer has spread into the thick muscle wall of the bladder (also called invasive cancer). It has not reached the fatty tissue surrounding the bladder and has not spread to the lymph nodes or other organs.

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Stage III: The cancer has spread throughout the muscle wall to the fatty layer of tissue surrounding the bladder. It may also have spread to the prostate (in men) or the uterus and vagina (in women). It has not spread to the lymph nodes or other organs.

Larger image

Stage IV: The tumor has spread through the bladder wall into the walls of the abdomen or pelvis, and/or it has spread to nearby lymph nodes. It may also be found in parts of the body far away from the bladder, such as the bones, liver, or lungs.

Larger image

Recurrent cancer: Recurrent cancer is when the cancer has recurred (returned) after it has been treated. It may come back in its original location or in another part of the body.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, www.springer-ny.com.

The treatment of bladder cancer depends on the size and location of the tumor, whether the cancer has spread, and the person’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

Early stage cancers can often be treated locally (treatments that just involve the bladder) without removing the whole bladder. More advanced cancers often need systemic chemotherapy, which are drugs that circulate through the body to kill cancer cells. In advanced bladder cancer, it may or may not be necessary to remove the bladder during surgery. Radiation may also be used as an alternative to bladder removal.

Surgery

There are different types of surgery for bladder cancer treatment, depending on the stage of the disease.

Transurethral resection of the bladder (TURB) with fulguration. This procedure is often used with early-stage cancers. The surgeon inserts a cystoscope (see Diagnosis) through the urethra into the bladder and removes the cancer using a tool with a small wire loop or using a laser or fulguration (high-energy electricity). This procedure is done with an anesthetic, so it is not painful.

Cystectomy. This procedure is often used with more advanced (deeply invasive) cancer or a noninvasive cancer that has recurred (come back after treatment). In a radical cystectomy, a surgeon removes the whole bladder and may also remove nearby tissue and organs. In men, the prostate and urethra may be removed. In women, the uterus, fallopian tubes, ovaries, and part of the vagina may be removed. In men and women, lymph nodes in the pelvis are also removed; this is called a pelvic lymph node dissection. Recent research suggests that doing a thorough pelvic lymph node dissection is beneficial. In some situations, the surgeon will remove just part of the bladder, called a partial or segmental cystectomy.

Urinary diversion. If the bladder is removed, the doctor will make a new way to pass urine out of the body, by using a section of the small intestine to divert urine to a stoma or ostomy (an opening) to the outside of the body. The patient wears a bag attached to the stoma to collect and drain urine.

Increasingly, surgeons can make a urinary reservoir, which is a storage pouch that sits inside the body. This is created using a part of the small or large intestine. In some cases, in men and women, the surgeon is able to connect the pouch to the urethra, creating a neobladder, in which case the patient can void (pass urine out of the body) normally. In other cases, the pouch is connected to the skin on the abdomen by a small stoma creating a type of continent urinary reservoir; no urinary pad is necessary. The patient drains the pouch periodically by inserting a catheter (a thin tube) through the small stoma and then removing the catheter and covering the stoma with a bandage.

The side effects of bladder cancer surgery depend on the procedure. Patients should discuss the details of their surgery with their doctor to understand exactly what side effects may occur. In general:

• TURB may cause mild bleeding and discomfort after surgery.
• 
  
  
• Following cystectomy and urinary diversion surgery, patients may experience infections or urine leaks, and if a neobladder is created, they may sometimes be unable to urinate or completely empty the bladder.
• 
  
  
• If the bladder is removed (cystectomy), men may be unable to have erections after surgery (impotence). Sometimes, a nerve-sparing cystectomy can be performed. When this is done successfully, men can potentially retain their normal erections.
• 
  
  
• Sometimes surgery damages the nerves in the pelvis and causes loss of sexual feeling and orgasm for both men and women. Often, these problems can be fixed. Patients should talk with their doctor about any side effects they are experiencing.

Bladder preservation or substitution

Living without the bladder can affect a patient's quality of life. Finding ways to keep all, or part, of the bladder is important whenever possible, especially for cases when removing the bladder will not extend life.

• For some patients, certain chemotherapy and radiation therapy treatment plans may be an alternative to removing the bladder.
• 
  
  
• As explained above, sometimes surgeons can use part of the intestine to create a substitute for the bladder, by making a neobladder or continent urinary reservoir. In this way, the patient does not need a urinary bag and can have a better quality of life.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation therapy given from a machine outside the body.

Doctors may use radiation therapy to treat bladder cancer that has invaded the bladder muscle:

• Before surgery to shrink a tumor or instead of surgery. In these cases, chemotherapy is often also given to enhance the effect of radiation therapy.
• 
  
  
• After surgery, to destroy any remaining tumor
• 
  
  
• To relieve symptoms, such as pain, bleeding, or blockage
• 
  
  
• To treat an isolated metastasis, such as a metastasis to the brain or the bone.

Radiation therapy can cause side effects near the area being treated. In bladder cancer, side effects most commonly occur in the pelvic or abdominal area and may include: patches of skin that look sunburned; bladder irritation, with the need to pass urine frequently during the treatment period; bleeding from the bladder or rectum; fatigue (tiredness); nausea; diarrhea; hair loss around the area treated; and stomach cramps.

Immunotherapy

Immunotherapy uses materials made by the body or in a laboratory to boost patients' natural defenses against cancer. It is also called biologic therapy or biologic response modifier (BRM) therapy. For many cancers, immunotherapy drugs are given intravenously. Currently, the most common immunotherapy drug for bladder cancer is BCG. A weakened bacterium called bacillus Calmette-Guerin (BCG), which is similar to a form of the germ that causes tuberculosis, is placed directly into the bladder through a catheter (called intravesical therapy; see below). BCG attaches to the inside lining of the bladder and attracts the patient's immune cells to the bladder to fight the tumor. BCG can cause flu-like symptoms, chills, mild fever, fatigue, a burning sensation in the bladder, and bleeding from the bladder. Interferon, another immunotherapy drug that can be given as intravesical therapy, is sometimes combined with BCG if the disease does not respond initially to BCG alone.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. For bladder cancer, doctors may decide to use one of two types of chemotherapy: intravesical (local) or systemic (whole body) treatment. In general, earlier-stage cancers are more likely to be treated with local chemotherapy and more advanced cancers with systemic chemotherapy.

Intravesical therapy. In this type of therapy, drugs are placed into the bladder through a catheter inserted in the bladder through the urethra. Local treatment kills only noninvasive tumor cells. It cannot reach tumor cells in the bladder wall or that have spread to other organs. The most common drug that is given in intravesical treatment is an immunotherapy drug called BCG (see above), other times, chemotherapy agents are used. The most common chemotherapy used is mitomycin C (Mitomycin, Mutamycin); thiotepa (Thioplex) and doxorubicin (Adriamycin, Rubex) have also been used. Intravesical therapy can cause bladder irritation, bladder infections, temporary inability to urinate, or blood in the urine. Rarely, patients experience fevers or chills.

Systemic chemotherapy. In this type of chemotherapy, patients receive drugs orally (by mouth) or intravenously (given through an IV). Intravenous chemotherapy is either injected directly into a vein or through a catheter. The drugs enter the bloodstream and travel to all parts of the body. Since most chemotherapy kills some healthy cells as well as cancer cells, side effects are common. Most side effects can be treated with medications and go away after treatment is over. Side effects of systemic chemotherapy can include nausea and vomiting, loss of appetite, hair loss, mouth sores, anemia (low blood cell count), fatigue, bleeding or bruising after minor injuries, and increased chance of infection.

In bladder cancer, many of the available chemotherapy regimens are still being tested in clinical trials to help determine which drugs, or which drug combinations, work the best in treating bladder cancer. Of the known drugs, usually a combination of drugs works better than one drug alone. The question of whether and in what situations is it best to give chemotherapy before or after surgery is also being tested in clinical trials.

A combination of drugs, called MVAC, has been used as the standard treatment for bladder cancer for many years, based on the results of clinical trials from the 1990s. MVAC has been useful in bladder cancer in delaying recurrence, extending life and sometimes achieving cure, but it has severe side effects. Other drugs are now in clinical trials to determine if there is a combination of drugs that works better and has fewer side effects. MVAC uses four drugs: methotrexate (MTX, Amethopterin, Rheumatrex, Trexall), vinblastine (Velban), doxorubicin (Adriamycin, Rubex), and cisplatin (Platinol). More recent clinical trials have shown that the combination of a newer drug gemcitabine (Gemzar), plus cisplatin, gives similar anticancer effects to the MVAC combination but with fewer side effects. Clinical trials are currently studying this new combination with the addition of other chemotherapy agents, such as paclitaxel (Taxol), docetaxel (Taxotere), and ifosfamide (Ifex).

Chemotherapy for locally advanced bladder cancer

Locally advanced bladder cancer refers to invasive bladder cancer that has spread beyond the boundaries of the bladder to surrounding organs or to the pelvic lymph nodes. Researchers are studying new combinations of chemotherapy that are more effective in managing bladder cancer. Treatments may include:

• Combinations of different drugs
• 
  
  
• Known drugs tested in different doses
• 
  
  
• Drugs or drug combinations given before or after surgery
• 
  
  
• Drugs or drug combinations given along with radiation therapy. If radiation therapy is combined with chemotherapy, it may make chemotherapy more effective through an effect called radiosensitizing.

Recently, an important clinical trial has shown that the use of intravenous chemotherapy (the MVAC regimen, mentioned above) before radical cystectomy improves survival for patients with invasive bladder cancer. It appears that this type of initial chemotherapy, termed neoadjuvant chemotherapy, shrinks the tumor within the bladder and may also kill small metastatic deposits of disease that have spread beyond the bladder. It is important to note that it does not appear that single-agent chemotherapy is helpful in improving the survival of patients with locally advanced bladder cancer.

Chemotherapy for metastatic bladder cancer

Metastatic bladder cancer refers to cancer that is diagnosed after it has spread beyond the lymph nodes. The term advanced bladder cancer may be used; this can also refer to a cancer that has recurred after all local treatments (such as a cystectomy or radiation therapy) have failed and which poses a serious threat to the patient's survival.

There are no methods to permanently cure metastatic bladder cancer in most people. In these cases, the goal of treatment switches to slowing the spread of cancer, achieving shrinkage of tumor (temporary remission), relieving symptoms, and extending life as long as possible. With advances in treatment, most patients with advanced bladder cancer can expect to live many months or even years-longer than they could just a few years ago. As outlined above, the MVAC and gemcitabine-cisplatin regimens are the current standard approaches in treatment; clinical trials are studying whether modifications of these regimens or the use of novel treatment regimens will improve survival rates, quality of life, and duration of life. Since there are relatively few treatment options for metastatic bladder cancer, clinical trials are often the best option for treatment. Clinical trials compare the best treatments available (standard treatments) with newer treatments that may be more effective. Investigating new treatments involves careful monitoring using scientific methods and all participants are followed closely to track progress.

The medications used to treat cancer are constantly being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.

Doctors and scientists are always looking for better ways to treat patients with bladder cancer. A clinical trial is a way to test a new treatment in order to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy drugs, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress is treating bladder cancer. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with bladder cancer.

To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient's options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are more common to bladder cancer and its treatments. For more detailed information on managing these and other side effects of cancer and cancer treatment, visit the Cancer.Net Managing Side Effects section.

Anemia. Anemia is common in patients with cancer, especially those receiving chemotherapy. Anemia is an abnormally low level of red blood cells (RBCs). RBCs contain hemoglobin (an iron protein) that carries oxygen to all parts of the body. If the level of RBCs is too low, parts of the body do not get enough oxygen and cannot work properly. Most people with anemia feel tired or weak. The fatigue (tiredness) associated with anemia can seriously affect quality of life and make it more difficult for patients to cope with cancer and treatment side effects.

Appetite loss. Appetite changes are common with cancer and cancer treatment, including chemotherapy. Individuals with a poor appetite or appetite loss may eat less than usual, not feel hungry at all, or feel satiated (full) after eating only a small amount. Ongoing appetite loss can lead to weight loss, malnutrition, and loss of muscle mass and strength. The combination of weight loss and loss of muscle mass, also called wasting, is referred to as cachexia.

Diarrhea. Diarrhea is frequent, loose, or watery bowel movements. It is a common side effect of certain chemotherapy or of radiation therapy to the pelvis, such as in women with uterine, cervical, or ovarian cancers.

Hair loss (alopecia). A potential side effect of radiation therapy and chemotherapy is hair loss. Radiation therapy and chemotherapy cause hair loss by damaging the hair follicles responsible for hair growth. Hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area. The hair may fall out entirely, gradually, or in sections. In some cases, the hair will simply thin-sometimes unnoticeably-and may become duller and dryer. Losing one's hair can be a psychologically and emotionally challenging experience and can affect a patient's self-image and quality of life. However, the hair loss is usually temporary, and the hair often grows back.

Infection. An infection occurs when harmful bacteria, viruses, or fungi (such as yeast) invade the body and the immune system is not able to destroy them quickly enough. Patients with cancer are more likely to develop infections because both cancer and cancer treatments (particularly chemotherapy and radiation therapy to the bones or extensive areas of the body) can weaken the immune system. Symptoms of infection include fever (temperature of 100.5°F or higher); chills or sweating; sore throat or sores in the mouth; abdominal pain; pain or burning when urinating or frequent urination; diarrhea or sores around the anus; cough or breathlessness; redness, swelling, or pain, particularly around a cut or wound; and unusual vaginal discharge or itching.

Menopausal symptoms in women. Up to 40% of women experience menopausal symptoms as a result of bladder cancer or its treatments. Menopausal symptoms may depend on the type of therapy and may include hot flashes; night sweats; vaginal dryness, itching, irritation, or discharge; painful sexual intercourse; difficulties with bladder control; depressed feelings; and insomnia.

Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by a chemotherapeutic drug directly, the reduced immunity brought on by chemotherapy, or radiation treatment to the head and neck area.

Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy.

Nervous system disturbances. Nervous system disturbances can be caused by many different factors, including cancer, cancer treatments, medications, or other disorders. Symptoms that result from a disruption or damage to the nerves caused by cancer treatment (such as surgery, radiation treatment, or chemotherapy) can appear soon after treatment or many years later. See Managing Side Effects: Nervous System Disturbances for the most common symptoms.

Pain. Depending on the stage of disease, 30% to 75% of all patients experience pain from cancer. About 85% to 95% of cancer pain can be treated successfully. Pain can make other aspects of cancer seem worse, such as fatigue, weakness, sleep disturbance, and confusion. Pain can come from the tumor itself or may be a result of cancer treatment. Pain from a tumor can be a result of the tumor growing and spreading to the bones or other organs and putting pressure on and damaging nerves. Pain from surgery is normal and may persist for months or years. Common procedures that cause pain afterward include mastectomy (removal of the breast and, occasionally, the surrounding tissue), chest surgery, neck surgery, and amputation of a limb (stump pain). Phantom pain is perceived pain in an organ or limb that has been removed. Pain may develop after radiation therapy and go away on its own. It can also develop months or years after treatment, especially after radiation therapy to the chest, breast, or spinal cord. Certain chemotherapy can cause pain along with numbness in the fingers and toes. Usually this pain goes away when treatment is finished, but sometimes the damage can be permanent.

Sexual dysfunction. Sexual dysfunction is common in all people, affecting up to 43% of women and 31% of men. It may be even more common in patients with cancer, as a result of treatments, the tumor, or stress. Many people, with or without cancer, find it intimidating to discuss sexual problems with their doctors. Sexual problems are most commonly caused by body changes from cancer surgery, chemotherapy or radiation therapy, hormone changes, fatigue, pain, nausea and/or vomiting, medications that reduce libido (desire for sex), fear of recurrence, stress, depression, and anxiety. Symptoms of sexual dysfunction generally fall into four categories: desire disorders, arousal disorders, orgasmic disorders, and pain disorders.

After treatment for bladder cancer ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years. For bladder cancer, follow-up care typically includes a general physical examination, cystoscopy, urine cytology, x-rays, and routine blood tests to make sure the bladder is properly functioning and to check for signs that the cancer has come back. Tell your doctor about any new symptoms, such as pain during urination, blood in the urine, frequent urination, or an immediate need to urinate. These symptoms may be signs that the cancer has come back or signs of other medical conditions.

For patients with a urinary diversion, follow-up care may include checking for infection with urine tests, checking and correcting problems of urinary continence (controlling urination), checking for recurrent cancer in the upper urinary tract, and checking for changes in kidney function with blood tests and x-rays.

People recovering from bladder cancer are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. For bladder cancer survivors who smoke, quitting smoking can help recovery and reduce the risk of cancer recurrence. Learn more about Quitting Smoking.

Moderate exercise can help you rebuild your strength and energy level. Talk with your doctor about helping you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment.

Research for bladder cancer is ongoing. The following advancements may still be under investigation in clinical trials and may not be approved or available at this current time. Always discuss all diagnostic and treatment options with your doctor.

Laparascopic cystectomy. There have been many innovations in surgery, and one of the important recent changes has been the demonstration that major operations (such as removal of the bladder) can sometimes be performed through smaller incisions. To do this, an instrument known as a laparoscope, which consists of a visual apparatus and cutting equipment housed in a flexible tube, is inserted through a much smaller incision than usual, and is used to surgically remove the bladder. While the operation usually takes longer than a standard approach to cystectomy, the incision is smaller and thus the recovery time may be shorter. Several studies are in progress to determine whether laparoscopic cystectomy is as safe as the standard "open" surgical approach and whether the cure rates are the same.

Photodynamic therapy (PDT). PDT may be useful in treating early stages of bladder cancer. During photodynamic therapy, a patient receives an injection of a nontoxic chemical, which collects in the tumor for a few days. The doctor then focuses a special laser light on the cancer, which changes the collected chemical to a new agent that can kill the tumor with very little harm to normal cells.

Molecular testing. Tests identifying genetic or protein abnormalities that signal bladder cancer may help predict a bladder cancer recurrence or predict which patients will need more aggressive forms of treatment. DNA abnormalities may also help predict prognosis of people with bladder cancer.

Targeted treatments. New treatments based on what is known about genetics and how changes in genes cause cancer to develop are already available for some cancers. These are called targeted treatments because they can pick out one signal, or target, in the process of cancer formation and repair it without killing healthy cells. Research is underway to determine how this approach may be useful in treating bladder cancer.

New chemotherapy/combinations. As described in the Treatment section, researchers are investigating new drugs and new combinations of current chemotherapy.

Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:

General questions

• What is my diagnosis?
  
  
• What is the stage of my cancer? What does this mean?
  
  
• What are my treatment options?
  
  
• What clinical trials are open to me?
  
  
• What treatment do you recommend? Why?
  
  
• What is the goal of this treatment?
  
  
• Do I need treatment right away?

For patients who need surgery

• Will my bladder be removed?
  
  
• Do you have experience with making urinary reservoirs, and can I have that type of surgery?
  
  
• What are the possible side effects of my surgery, in the short term and the long term?
  
  
• Will I need to stay in the hospital for this surgery? If so, for how long?

For patients who need chemotherapy/immunotherapy

• What type of therapy will I be receiving?
  
  
• How will it be delivered (through an IV, a catheter, or a pill)?
  
  
• What does the preparation for this treatment involve?
  
  
• What side effects can I expect from this treatment?
  
  
• What can be done to relieve the side effects?

For patients who need radiation therapy

• What type of radiation therapy is recommended?
  
  
• What is the goal of the radiation therapy?
  
  
• How long will it take to give the radiation therapy?
  
  
• What side effects can I expect from this treatment?
  
  
• What can be done to relieve the side effects?

After treatment

• What are the chances that the tumor will return?
  
  
• What follow-up tests do I need, and how often do I need them?

American Urological Association Foundation
1000 Corporate Blvd., Ste. 410
Linthicum, MD  21090
Toll Free: 800-828-7866
Phone: 410-689-3990
www.UrologyHealth.org

Bladder Cancer Advocacy Network (BCAN)
4813 St. elmo Ave.
Bethesda, MD  20814
Phone: 301-215-9099
www.bcan.org

National Cancer Institute (NCI)
Public Inquiries Office
Bldg. 31, Rm. 10A31
31 Center Dr., MSC 2580
Bethesda, MD  20892-2580
Phone: 301-435-3848
Toll Free: 800-4-CANCER
TTY: 800-332-8615
www.cancer.gov

United Ostomy Associations of America (UOAA)
P.O. Box 66
Fairview, TN  37062-0066
Toll Free: 800-826-0826
www.uoaa.org

View all of Cancer.Net's Patient Information Resources.