Bladder Cancer

WHAT IS BLADDER CANCER?
Bladder cancer is a disease in which malignant (cancer) cells form in the tissues of the bladder.
The bladder is a hollow organ in the lower part of the abdomen. It is shaped like a small balloon and has a muscular wall that allows it to get larger or smaller. The bladder stores urine until it is passed out of the body. Urine is the liquid waste that is made by the kidneys when they clean the blood. The urine passes from the two kidneys into the bladder through two tubes called ureters. When the bladder is emptied during urination, the urine goes from the bladder to the outside of the body through another tube called the urethra.

There are three types of bladder cancer that begin in cells in the lining of the bladder. These cancers are named for the type of cells that become malignant (cancerous):
Transitional cell carcinoma: Cancer that begins in cells in the innermost tissue layer of the bladder. These cells are able to change shape depending on whether the bladder is full or empty and may be stretched without breaking apart. Most bladder cancers begin in the transitional cells.
Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells that may form in the bladder after long-term infection or irritation.
Adenocarcinoma: Cancer that begins in glandular (secretory) cells. Glandular cells in the lining of the bladder produce and release fluids such as mucus.
Cancer that is confined to the lining of the bladder is called superficial bladder cancer. Cancer that begins in the transitional cells may spread through the lining of the bladder and invade the muscle wall of the bladder or spread to nearby organs and lymph nodes; this is called invasive bladder cancer.
WHAT ARE THE RISK FACTORS FOR BLADDER CANCER?
Smoking, gender, and diet can affect the risk of developing bladder cancer.
Risk factors include the following:
Smoking.
Being exposed to certain substances at work, such as rubber, certain dyes and textiles, paint, and hairdressing supplies.
A diet high in fried meats and fat.
Being older, male, or white.
Having an infection caused by a certain parasite.
CAN BLADDER CANCER BE FOUND?
Screening
Screening tests or examinations are used to look for a disease in people who have not had that disease before and do not have any symptoms of that disease. Doctors do not specifically screen people for bladder cancer and it is not recommended by any professional organization. A routine urinalysis, however, might find blood in the urine, which can be a sign of bladder cancer. Once a person is diagnosed with bladder cancer, then their doctor will test them periodically to check for recurrence of the cancer.
Possible signs of bladder cancer include blood in the urine or pain during urination.
These and other symptoms may be caused by bladder cancer or by other conditions. A doctor should be consulted if any of the following problems occur:
Blood in the urine (slightly rusty to bright red in color).
Frequent urination, or feeling the need to urinate without being able to do so.
Pain during urination.
Lower back pain.
Tests that examine the urine, vagina, or rectum are used to help detect (find) and diagnose bladder cancer.
The following tests and procedures may b
Bladder tumor marker studies: These are chemical or immunologic (using antibodies) tests to detect specific substances released by bladder cancer cells into the urine. Some doctors find these tests useful, but most feel more research is needed before they should be used routinely.
Computed tomography (CT): The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, as does a conventional x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body (think of a loaf of sliced bread). The machine will take pictures of multiple slices of the part of your body that is being studied. Often after the first set of pictures is taken you will receive an intravenous injection of a "dye" or radiocontrast agent that helps better outline structures in your body. A second set of pictures is then taken.
CT scans take longer than regular x-rays and you will need to lie still on a table while they are being done. But just like other computerized devices, they are getting faster and your stay might be pleasantly short. The newest CT scanners take only seconds to complete the study. Also, you might feel a bit confined by the ring-like equipment you抮e in when the pictures are being taken.
The contrast "dye" is injected through an IV line. Some people are allergic to the dye and get hives, a flushed feeling, or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell your doctor if you have ever had a reaction to any contrast material used for x-rays. If you have, you may need medicine before you can have such an injection during your test.
You may also be asked to drink a contrast solution. This helps outline your intestine if your doctor is looking at organs in your abdomen. The CT scan will provide precise information about the size, shape, and position of a tumor, and can help find enlarged lymph nodes that might contain cancer.
Magnetic resonance imaging (MRI) scans: This procedure is similar to a CT scan, but uses powerful magnets and radio waves instead of x-rays to take detailed cross-sectional images. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. Not only does this produce cross sectional slices of the body like a CT scanner, it can also produce slices that are parallel with the length of your body.
If your doctor suspects that the cancer has spread beyond the bladder, MRI scans are sometimes used to detect cancer in tissues next to the bladder, in nearby lymph nodes, or in distant organs. In such cases, either a CT or MRI scan may be used.
A contrast material might be injected just as with CT scans, but is used less often. MRI scans take longer -- often up to an hour. Also, you have to be placed inside a tube-like piece of equipment, which is confining and can upset people with claustrophobia. The machine makes a thumping noise that you may find annoying. Some places will provide headphones with music to block this out. MRI images are particularly useful in examining pelvic tumors. MRI scans are also helpful in detecting cancer that has spread to the brain or spinal cord.
Ultrasound: This test, also known as ultrasonography, uses sound waves to create "echoes" of internal organs. The pattern of echoes reflected by tissues can be useful in determining the size of a bladder cancer and whether it has spread beyond the bladder.
Bone scans: In this imaging test, a small amount of a radioactive substance is injected into a vein. This substance accumulates in areas of bone where the cancer has spread. These areas can then be looked at with a special camera. However, other cancers and some noncancerous bone diseases can also cause abnormal bone scan results.
Positron Emission Tomography (PET) scans: PET scanning is a technique that uses radioactive substances to show areas of cancer that may not otherwise be seen on more usual tests such as CT scan or MRI. It may also be able to distinguish benign tumors or masses from cancerous ones.
Although PET scans are being used as part of research projects in bladder cancer, it is not yet certain how valuable they are in helping to manage the care of patients with bladder cancer.
Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy for bladder cancer is usually done during cystoscopy. It may be possible to remove the entire tumor during biopsy.
Urine cytology: Examination of urine under a microscope to check for abnormal cells.
Bladder cancers are graded, from 1 to 4, based on how they look under the microscope.
Low-grade (1) cancers look more like normal bladder tissue. They usually have a good prognosis. These are called well-differentiated cancers.



Normal urothelium with umbrella cells covering the orderly epithelial layer of urothelial (transitional) cells. Nuclei are regular and bland and cytoplasm is abundant (magnification 200_)
Low-grade papillary urothelial carcinoma. A low-power view demonstrates the papillary configuration and architectural disorder. The urothelial layer often is thickened, and papillary fronds may be partially fused (magnification 25_).
Low-grade papillary urothelial carcinoma. A high-power view demonstrates the cytologic atypia present in low-grade urothelial carcinoma. Nuclear pleomorphism and hyperchromasia are demonstrated within a disordered urothelial layer (magnification 400_)

Grade 2 cancers are called moderately differentiated.
High-grade (3-4) cancers look less like normal tissue. They are more likely to invade the bladder wall and to spread outside the bladder and tend to be associated with a less favorable prognosis. These cancers are called either poorly differentiated or undifferentiated.



Normal urothelium (400?). The larger umbrella cell layer can be easily seen, covering a normal appearing urothelium. Slight nuclear irregularities within the urothelial cell layer, often previously termed mild dysplasia, should be classified as normal
High-grade papillary urothelial carcinoma. Increased architectural and cytologic disorder is apparent even at low power. Marked variation is noted in cellular and nuclear details, and cellular dyscohesion is apparent (magnification 100_)
High-grade papillary urothelial carcinoma. A high-power view of the marked cytologic and nuclear atypia present. Numerous cells are separated from the urothelial component (magnification 400_)
It is not unusual for people with one bladder cancer to develop additional cancers in other areas of the bladder or elsewhere in the urinary system. For this reason, the doctor may biopsy several different areas of the bladder lining.

HOW IS BLADDER CANCER TREATED?
Once your cancer has been diagnosed and staged, you must make a decision quickly, but it is important to give yourself time to absorb the information you have just learned.
You will want to weigh the benefits of each treatment against its possible side effects and/or risks. The treatment you choose should also take into account your general health, age, and personal preferences, as well as the cell type and stage of your cancer.
The main types of treatment for cancer of the bladder are surgery, radiation therapy, immunotherapy, and chemotherapy. Based on the stage of the cancer, one type or a combination of types of treatment may be recommended.
Surgery
Transurethral surgery: For early stage or superficial bladder cancers, a transurethral resection (TUR) is most common. This means that the operation is done using a cystoscope placed into the bladder through the urethra while you are under regional or general anesthesia. For this surgery there is no need to cut into the abdomen.
After surgery, additional steps may be taken to ensure that the tumor has been completely destroyed. Any remaining cancer may be treated using the cystoscope and burning the base of the tumor (fulguration). Cancer can also be destroyed using the cystoscope and a high-energy laser.
The side effects of transurethral bladder surgery are generally mild and do not usually last long. There may be some bleeding and discomfort right after surgery.
Cystectomy: When the bladder cancer is invasive, the diseased area is removed by cutting completely through the bladder wall. For this surgery, it is necessary to cut through the abdomen. In rare cases if the cancer is not very large, it may be possible to remove it and only part of the bladder. This operation is called a partial cystectomy.
Recent studies have shown that patients with this more conservative approach to locally advanced bladder cancer have done well, and that patients who do not respond to the treatment can have their bladders removed with a radical cystectomy at a later date.
If the cancer is larger or if more than one area of cancer is present, a radical cystectomy is done.
General anesthesia is used for a partial or radical cystectomy. You will need to stay in the hospital for about 7 to 10 days. You can usually go back to your usual activities in about 4 to 6 weeks.
The complications and side effects of a radical cystectomy (removing the bladder and nearby organs) are more serious. There is a risk of excessive bleeding, urinary tract infections, urine leakage (incontinence), and blockage of urine flow.
Reconstructive surgery: If your whole bladder is removed, you will need another way to store and remove urine. Several types of reconstructive surgery can be done depending on your medical situation and personal preferences.
One possibility is a urostomy. In this situation the urine drains into a bag attached to the outside of the abdomen. In the ileal conduit procedure, a short piece of the small intestine (small bowel) or part of the large intestine (colon) is removed and relocated as a passageway (conduit) for urine to pass from the kidneys to the outside of the body.
Another type of urostomy is the continent diversion. Here, the pouch created from the piece of intestine has a valve created.
New methods or reconstructive surgery can route the urine back into the urethra, restoring close to normal urination. One method is the creation of what is called a neobladder in which a urinary reservoir made of a piece of intestine is sewn to the urethra. This allows the patient to urinate normally.
Sexual Effects of Radical Cystectomy and Urostomy
After radical bladder surgery, a man no longer produces semen, because this operation also removes the prostate gland, which produces most of the seminal fluid. The sperm cells made in his testicles mature but they have no way to exit the body. Instead, the body simply reabsorbs the sperm cells with no ill effects.
It is common for men to have nerve damage that often causes them to become impotent, or unable to have an erection. This function may return with time.
It is normal to have concerns about your sex life after having a urostomy. With some simple planning, sex can be pleasurable and less stressful. Having your appliance fit correctly and emptying it before sexual activity, reduces the chances of a major leak. A pouch cover or small ostomy pouch can be worn during intercourse. Even a sash can keep the pouch out of the way. Wearing a T-shirt may be even more comfortable. To reduce rubbing against the appliance, choose positions for sexual activity that keep your partner's weight off the appliance.
Intravesical Immunotherapy
Intravesical therapy means that a treatment is placed directly into the bladder through a catheter rather than being given by mouth or injected into a vein. The most common form of intravesical therapy used in bladder cancer is immunotherapy. This treatment causes the body's own natural defenses (immune system) to attack the bladder cancer.
Bacillus Calmette-Guerin (BCG) is considered the most effective intravesical immunotherapy that is very useful for treating low-stage bladder cancer. BCG, a bacterium that is sometimes used to vaccinate people against tuberculosis, is given directly into the bladder through a catheter. The body's immune system responds to BCG. Immune system cells are attracted to the bladder and activated by BCG, which in turn affects the bladder cancer cells. It is usually given once a week for 6 weeks. Sometimes long-term "maintenance" BCG therapy is given. BCG therapy may be given along with a transurethral resection of the tumor.
Treatment with BCG may cause flu-like symptoms (mild fever, chills, and fatigue), as well as a burning sensation in the bladder. A persistent high fever may indicate life-threatening spread of BCG infection throughout the body. In such cases, prompt medical care should be sought. Usually these infections respond to treatment with an antibiotic drug used to treat tuberculosis called isoniazid.
Interferon Therapy
Interferons are a family of substances naturally produced by several types of cells. Interferon-alpha is the type most often used in treating bladder cancer. Interferon is occasionally used in the intravesical treatment of bladder cancer.
Possible side effects include muscle aches, bone pain, headaches, problems with thinking and concentration, fatigue, nausea, and vomiting. These problems are temporary and usually improve after treatment is completed. Other drugs may be given along with the interferon to lessen these side effects.
Chemotherapy
Chemotherapy is the use of medicines to treat disease. In cancer treatment, chemotherapy uses anticancer medications to destroy cancer cells.
The effect chemotherapy has on normal cells depends on which medication is used, the dose of the medication, how the medication is introduced into the body, as well as the individual patient. Chemotherapy used to treat bladder cancer can be either intravesical or systemic (affecting cells throughout the body).
Chemotherapy may be used to shrink a large tumor so that it can be removed by surgery or a less extensive operation. When chemotherapy is given before surgery, this is known as neoadjuvant chemotherapy. It can also be given after surgery or radiation (as adjuvant therapy) to prevent the growth of stray cancer cells remaining in the body. IN most cases, these stray cancer cells cannot be recognized by routine tests such as x-rays but are assumed to be present.
Intravesical chemotherapy: In intravesical chemotherapy, a urinary catheter is used to place anticancer drugs directly into the bladder. These medications reach cancer cells near the bladder lining but do not reach cancer cells that are in the kidneys, ureters, and urethra, cancer cells that may have invaded deeply into the bladder wall, or cancer cells that have spread to other organs.
For this reason, intravesical chemotherapy is used only for noninvasive (stage 0) or minimally invasive (stage I) bladder cancers. This treatment uses drugs that kill actively growing cancer cells. Many of the same drugs are given systemically (by mouth or into a vein) to treat more advanced stages of bladder cancer. Mitomycin and thiotepa are the drugs used most often for intravesical chemotherapy.
One of the main advantages of intravesical chemotherapy is that the drugs do not usually spread throughout the body. This limits the unwanted side effects that can occur with systemic chemotherapy, which affects other organs. Thiotepa, which is less often used, has occasionally been absorbed from the bladder and caused toxicity in the rest of the body.
The main side effects of intravesical chemotherapy are irritation and a burning feeling in the bladder.
Systemic chemotherapy: Systemic chemotherapy uses anticancer drugs that are injected into a vein or given by mouth. These medicines travel through the bloodstream to all parts of the body. In contrast to intravesical chemotherapy, systemic chemotherapy can attack cancer cells that have already spread beyond the bladder to lymph nodes and other organs.
These drugs kill cancer cells but can also damage some normal cells. This damage to normal cells can cause side effects.
A combination of chemotherapy drugs is more effective than any single drug in treating bladder cancer. Chemotherapy combinations are often abbreviated by the first letter of each of the drugs. The combinations used most often for bladder cancer are:
M-VAC (methotrexate, vinblastine, doxorubicin [Adriamycin], and cisplatin) and
MCV (methotrexate, cisplatin, and vinblastine).
GemCIS (gemcitabine and cisplatin)
Other drugs sometimes used in systemic chemotherapy of bladder cancer include cyclophosphamide and paclitaxel.
Factors that help determine whether or not a person will respond to chemotherapy include the patient’s performance status (how well they can accomplish activities of daily living, among other things), whether the cancer has spread to organs such as the liver, lung or bone, and whether certain blood test results are elevated.
Newer agents, including docetaxel, gemcitabine, and paclitaxel, as first-line agents, had response rates of 40% to 70% with potentially less toxicity. For example, isofamide + paclitaxel + cisplatin resulted in 79% of response rate in 29 patients with untreated advanced patients.
There are other types of bladder cancer, including squamous cell carcinoma and adenocarcinoma that occur uncommonly in the bladder. These types of cancers are usually treated with drugs that work on the same types of tumors elsewhere in the body.
Chemotherapy drugs kill cancer cells but also damage some normal cells. Therefore, careful attention must be given to avoiding or minimizing side effects, which depend on the type of drugs, the amount taken, and the length of treatment. Temporary side effects might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores.
Because chemotherapy can damage the blood-producing cells of the bone marrow, it may lower the patient抯 blood cell counts. This can result in:
infection (due to a shortage of white blood cells)
bleeding or bruising after minor cuts or injuries (due to a shortage of blood platelets)
fatigue (due to low red blood cell counts)
Most side effects disappear once treatment is stopped. There are treatments that can prevent or lessen most of the immediate side effects. For example, several drugs (antiemetics) can prevent or reduce nausea and vomiting.
A new group of drugs called growth factors can help the bone marrow recover after chemotherapy and can treat problems resulting from low blood counts. Some growth factors increase production of white blood cells by the bone marrow. These drugs are sometimes used to prevent or treat infections in patients with low white blood cell counts. Anemia (too few red blood cells) may be treated with red blood cell transfusions or with erythropoietin, a growth factor that increases production of red blood cells.
Radiation Therapy
Radiation therapy uses high-energy radiation to kill cancer cells.
External beam radiation therapy focuses radiation from outside of the body on the cancer. Local or interstitial radiation therapy uses a small pellet of radioactive material placed directly into the cancer.
After surgery, radiation can kill small deposits of cancer cells that may not be visible during surgery. The combination of radiation therapy and chemotherapy given after transurethral bladder surgery is sometimes able to completely destroy cancers that would otherwise require cystectomy for complete removal. Thus a bladder-sparing approach helps avoid the substantial physical and emotional consequences of bladder removal.
If a tumor is positioned so that surgery is difficult, radiation may be used before surgery to shrink the tumor, making surgery easier. This is done less often these days than in the past. Radiation also might be used to ease (palliate) the symptoms of advanced cancer, such as urine blockage, bleeding, and pain.
Mild skin irritation, nausea, bladder irritation, diarrhea, or fatigue may occur following radiation therapy. These symptoms are usually temporary. If you have these or other side effects from radiation therapy, you should discuss them with your health care team. They can suggest ways to lessen many of these discomforts.
Photodynamic therapy
Photodynamic therapy is a relatively new weapon in the fight against bladder cancer. In photodynamic therapy (PDT), photosensitizers, or light-sensitive molecules, are injected into the bloodstream and absorbed by cells throughout the body. These agents remain in cancer cells longer than in normal cells. A cystoscope is then inserted through the urethra into your bladder, where it shines a red laser light onto the tumor. When the cancer cells are exposed to laser light, the photosensitizers are activated and cause cell damage and death. Effectiveness
Photodynamic therapy is only effect against superficial forms of bladder cancer. Its effects do not penetrate to deeper areas of the bladder.Side Effects
Phototherapy may cause the following side effects:
Severe photosensitivity (greatly increased tendency to sunburn)
Flu-like symptoms (achiness, fatigue)
Fever, chills
Nausea
Urinary symptoms:
Frequent need to urinate
Urgent need to urinate
Pain/burning with urination
Blood urine
Special Considerations
Because photodynamic therapy makes you more sensitive to sunlight, check with your doctor regarding appropriate sun precautions. You should avoid being outside during the sunniest times of day (about 10 in the morning until late afternoon). If you do have to go outside, always use a sun block with SPF of at least 30, and wear protective clothing and a wide-brimmed hat.
Treatment Options by Stage
Most of the time the doctor only knows the clinical stage ?that is, the size of the bladder tumor and how deep into the bladder wall it penetrates. It is unlikely that the doctor would know whether the cancer has spread to lymph nodes unless they are very large and show up on an imaging study.
Stage 0
This early stage of bladder cancer is almost always first treated with transurethral resection (TUR) alone, or TUR followed by intravesical immunotherapy, or intravesical chemotherapy.
Intravesical therapy is usually not given for stage 0a bladder cancer unless the cancer is classified as high grade (its cells look very abnormal under a microscope).
Intravesical immunotherapy or chemotherapy is usually recommended for stage 0is (flat carcinoma in situ).
The prognosis for people with stage 0a bladder cancer is excellent. These noninvasive papillary cancers are nearly always cured by appropriate treatment and long-term follow-up care. Although you are likely to develop one or more superficial cancers elsewhere in your urinary system, these new cancers are rarely deeply invasive or life threatening. The 5-year survival rate for stage 0a cancer is better than 95%.
The long-term prognosis for stage 0 is bladder cancer (also known as carcinoma in situ or flat non-invasive cancer) is not quite as favorable, because the cancer has a greater risk of eventually developing into a cancer with muscle invasion. The 5-year survival rate is also about 95%.
For the patients with unresectable bladder cancer, Photodynamic therapy may be choice.
Stage I
Treatment options are the same as for stage 0 bladder cancer. In rare instances, radiation therapy might be used.

Stage II
Radical cystectomy, with or without removal of nearby lymph nodes, is recommended for most patients with stage II bladder cancer. In some patients, partial cystectomy or TUR with fulguration may be suitable, but patients must be carefully evaluated before this choice is made.
Although cancer at this stage shows no recognizable spread beyond the bladder, in some cases, there may be tiny deposits of cancer (micrometastases) growing elsewhere in the body that are too small to detect by staging tests. These micrometastases may eventually grow to become life threatening. This risk is greater with more deeply invasive cancers and higher-grade cancers. Often chemotherapy is given either before surgery (neoadjuvant) or after (adjuvant) to lower the chance the cancer will come back in a distant site.
Another option is radiation, combined with intravenous chemotherapy after transurethral resection. This bladder-sparing approach may be as effective as surgery for cancers that are not too large. If the cancer recurs and cannot be controlled by local treatment, cystectomy can still be done. The disadvantage is that you will have to undergo frequent and careful follow-up examinations. Sometimes radiation is given first and followed with chemotherapy.
Radiation is a reasonable treatment instead of radical cystectomy for patients who cannot undergo a major operation because of other serious medical conditions.
Stage III
Radical cystectomy, with or without removal of nearby lymph nodes, is recommended for most patients with stage III bladder cancer. Radiation is a reasonable alternative to radical cystectomy if you cannot undergo a major operation because of other serious medical conditions. Partial cystectomy is seldom an option for patients with stage III bladder cancer.
Stage IV
For stage IV bladder cancers without distant metastases, the two main options are radical cystectomy or external beam radiation therapy. Systemic chemotherapy may be given as well.
For stage IV bladder cancers with distant metastases, options include radical cystectomy, external beam radiation therapy, and systemic chemotherapy, given alone or along with these other treatments.
Recurrent Bladder Cancer
Prognosis and treatment depend on the type of prior treatment, and the location and extent of the recurrent cancer.
For example, it is not uncommon for superficial bladder cancers to recur locally in the bladder, either in the same site as the original cancer or at other sites in the bladder. These tumors are evaluated and treated the same way as the original tumor. On the other hand, tumors that recur in distant sites may require other treatment, such as chemotherapy or radiation therapy.

WHAT IS PROGNOSIS OF BLADDER CANCER?
Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) depends on the following:
The stage of the cancer (whether it is superficial or invasive bladder cancer, and whether it has spread to other places in the body). Bladder cancer in the early stages can often be cured.
The type of bladder cancer cells and how they look under a microscope.
The patient’s age and general health.
Treatment options.
CAN AN BLADDER CANCER BE PREVENTED?
At this time, there is no certain way to prevent bladder cancer. The best plan is to avoid risk factors when that is possible.
Do Not Smoke
Smoking is believed to cause nearly half the deaths from bladder cancer among men and more than a third among women.
Avoid Occupational Exposure to Certain Chemicals
If you work with a class of chemicals called aromatic amines, be sure to follow good work safety practices. Industries where these chemicals are commonly used include the makers of rubber, leather, printing materials, textiles, and paint products.
Drink Plenty of Liquids
There is some evidence that drinking large amounts of fluids- mainly water- can lower a person risk of bladder cancer.
Diet
A diet high in fruits and vegetable seems to protect against bladder cancer.