BLADDER CANCER - A REVIEW

Introduction

Cancer of the bladder is the fourth most common cancer among men and the ninth most common cancer among women. About 38,500 men and 13,000 women will develop the disease each year. Cancer of the bladder may occur at any age, but it usually strikes those over 50 years old.

If detected and treated early, bladder cancer is almost always cured (the 5 year survival rate of early bladder cancer is 90%). Unfortunately, less than one in ten patients with advanced bladder cancer survive five or more years. Each year about 6,000 men and 3,000 women will die of the disease. During the past 30 years, the death rate for bladder cancer has declined slightly for men, more so for women.

What the bladder does

The bladder is a muscular sack that collects and stores urine. It is hollow and its shape depends on how much urine it holds. When it is empty it looks like a deflated balloon. As it fills, it becomes rounded and pushes up against the abdomen.

The bladder is lined by special cells, called transitional cells. These cells are unique in that they have the ability to expand and deflate, which makes sense as the bladder fills and empties of urine. Almost all bladder cancer arise in this lining layer. These cancers in time can grow and spread into the underlying bladder muscle. Cancers originating in the bladder muscle are very rare.

Urine is made up of wastes removed from the blood. This is done by the kidneys. The urine then travels down tubes known as ureters and then is stored in the bladder until it can be released from the body through another tube, the urethra.

What is cancer?

Cancer is a disease caused by the abnormal growth of cells. Cancer can occur in any part of the body. Normally the cells that make up the different parts of the body divide and reproduce in an orderly manner, so that we can grow, replace worn-out body tissue, and repair injuries. Sometimes, however, cells get out of control, divide more than they should, and form masses known as tumors.

Some tumors may interfere with body functions and need to be removed, but do not spread to other parts of the body. These are known as benign tumors. Malignant, or cancerous tumors, not only invade or destroy normal body tissue, but cells break away from the original tumor and go to other parts of the body. There they may form additional malignant tumors. This process is known as metastasis.

If bladder cancer spreads, it usually goes first to the lymph nodes in the pelvis. Bladder cancer also tends to spread to the lungs, liver, and bones.

Types of bladder cancer

Bladder cancers are classified according to the type of cell that has become cancerous and the grade. Generally, low-grade tumors are slow-growing, while high-grade tumors grow more quickly and are more likely to spread. Knowing the cell type and grade of bladder cancer are important in planning the right treatment. About 90% of cancers of the bladder involve transitional cells. Transitional cells are merely the name of the usual cell that lines the bladder wall and are not changing as the name would imply. Transitional cells are unique to the urinary tract and line the kidneys and ureters as well.

Other types of cells that cause bladder cancer include squamous cell cancers or adenocarcinomas.

Transitional-cell cancers of the bladder can be further divided into 'papillary' or 'solid' tumors.

Papillary, which means 'finger-like' are usually low grade which means that they grow slowly. Papillary tumors also usually grow towards the inside of the bladder, not towards the muscle lining. Sometimes, particularly if untreated, papillary tumors will invade into the bladder muscle and then spread into the body. Papillary tumors occur more than twice as often as solid tumors. There may be one papillary tumor or several. Patients with tumors in multiple areas are more likely to have the cancer come back, or recur, after treatment. In general, papillary cancers of the bladder have a recurrence rate of up to 50%. That means even if all the cancer is removed, new cancers will develop in other parts of the bladder in at least one-half of all patients at a later time. These recurrences can occur at any time within ten years, but usually within two years.

The solid tumors are usually high-grade and invade the bladder muscle very early. As mentioned earlier, cancers that have invaded the bladder wall are also more likely to spread beyond the bladder.

Who is at risk of developing bladder cancer?

Smokers are three times as likely to develop bladder cancer as nonsmokers. This link between smoking and bladder cancer is especially strong among men.

Bladder cancer is more common in highly industrialized areas and among workers exposed to certain chemicals. Certain aniline derivatives, benzidine, 2-napthylamine, and other chemicals used in dye manufacturing increase the risk to workers involved in the process. Painters and workers in the rubber, metal, textile, and leather industries are also at high risk.

The artificial sweeteners saccharin and cyclamates have been shown to cause bladder cancer in animals when given in very large doses. The link between these sweeteners and bladder cancer in humans has not been shown.

In the Middle East and Africa, certain parasitic worm infections have been linked with bladder cancer.

Signs and symptoms

Blood in the urine is usually the first sign of bladder cancer. Many times, blood in the urine cannot be noticed by the individual, but is found by urinalysis done as part of a regular checkup or treatment for another medical condition. If blood can be seen in the urine, it may change the color of the urine from smoky to rusty to bright red. The blood may disappear for days or even weeks, only to reappear. Blood in the urine can be caused by a number of medical problems besides cancer. These include infection, benign tumors, and stones. If blood is noticed, a doctor should be consulted to determine its cause.

Early stage bladder cancer does not usually cause pain, but pain may sometimes occur along with the bleeding. The need to urinate may seem more urgent and frequent. Signs of late stage bladder cancer may include all of the above plus possible bowel problems, loss of appetite, and weight loss. Pain may be felt in the lower back and in the bones.

How the diagnosis is made

The diagnosis of bladder cancer begins with a complete medical history. The doctor will ask questions about the patient's overall health and bladder cancer risk factors, such as smoking and exposure to certain industrial chemicals.

To determine if cancer is present, some or all of the following tests may be done:

Urinalysis

is the complete analysis of the physical and chemical properties of a sample of urine. As part of the diagnostic workup for bladder cancer, it can reveal blood in the urine in amounts too small to be noticed by the patient, or can confirm that blood is still in the urine.

Intravenous pyelogram (IVP)

can help determine the source of the bleeding. A small amount of special X-ray dye is injected into the bloodstream. This dye is quickly absorbed by the kidneys. X-rays are then taken to track the dye as it makes its way through the urinary system. The images displayed on the X-rays can locate tumors and other sources of bleeding.

Cystoscopy

permits the doctor to actually look inside the bladder. A small slender tube, the cystoscope, is inserted into the bladder through the urethra, the final portion of the urinary system. The cystoscope is fitted with a lens and a light which allows the doctor to carefully examine the inner surface of the bladder and look for any abnormal areas.

Biopsy

is the removal and examination under a microscope of suspicious looking areas from the bladder. The cells are removed through the cystoscope. Since bladder cancer may be present in more than one area of the bladder, several samples of cells--from both normal and abnormal looking areas--will be removed for examination. Only a biopsy can tell for sure whether cancer is present.

CYTOLOGY is the study of individual cells. The inside of the bladder is irrigated with a salt-water solution. The cells suspended in the solution are examined for any abnormalities. PAP smear is an example of cytology when we look at scrapings from the female cervix.

Bimanual abdominal and rectal examination lets the doctor feel for any hard areas in part of the bladder. The doctor inserts a gloved finger into the vagina or rectum and then presses down gently on the abdomen. A hardened spot that can be felt may be a sign of a tumor.

Staging the disease

If the biopsy shows that the patient has bladder cancer, additional tests are done to see if the disease has spread to other parts of the body. The process of determining the extent of a tumor and planning the right treatment is known as STAGING the disease.

Because bladder cancer most often spreads to the lungs, liver, and bones, these areas are examined. This is done by chest x-ray, bone scans and CT or CAT (computed axial tomography) scans.

For a bone scan, the patient swallows or is injected with a small amount of radioactive material. (This does not mean the patient will become radioactive.) The way the material is absorbed by the cells of the bone can indicate if a tumor is there. A special camera tracks the material and displays the image on a screen.

ACT or CAT scan takes x-rays from different angles around the body. A computer then compiles all these images into a complete picture of a cross-section of the body. CAT scans of the pelvis and abdomen can be helpful in evaluating a bladder tumor, looking for enlarged lymph nodes, and planning radiation treatment.

Aspiration node biopsy

* The only way to tell for sure if cancer has spread to the lymph nodes is to biopsy the nodes themselves. This may be done by inserting a needle into nodes that appeared abnormal on x-rays or CAT scans, and withdrawing some cells. Because the cells are drawn out by a needle, this procedure is known as needle aspiration.

Pelvic Lymphadenectomy

* Surgery is usually needed to get samples of the lymph nodes in the pelvis. This procedure is known as pelvic lymphadenectomy. This can often be done with a special telescope or laparoscope inserted into the abdomen.

Treating the disease

Surgery, alone or combined with other therapies, is used to treat more than 90% of bladder cancer patients. Radiation and chemotherapy can increase the chances for a cure, help control metastatic disease, and prevent the disease from recurring, but are usually not used as the main or only treatment.

Surgery

Surgery for early or superficial bladder cancer

Most early bladder cancers are biopsied and removed through an endoscope, a thin telescopic tube inserted into the urethra and then into the bladder. This is usually referred to as 'transurethral resection'. This type of removal is effective for those cancers, usually the papillary type, which have NOT invaded into the bladder muscle. An electric cutting knife 'or loop' attached to the endoscope is used to remove the tumors. In some instances, lasers, or very intense light beams, are being used to destroy bladder tumors. Several tumors may be removed during a single operation and the procedure can be repeated as often as necessary. An anesthetic, such as general anesthesia or spinal, is necessary for any transurethral resection.

Surgery for advanced or deep bladder cancer

Patients with more advanced disease, that which has grown into the bladder muscles, often need to have the bladder removed, a procedure known as a total or radical cystectomy. This of course means that the urine must be diverted away from the bladder. Options for diversion are discussed below.

Patients who have had superficial bladder tumors removed transurethrally and, despite further treatment, continue to develop many tumors scattered over the lining of the bladder are at high risk of developing invasive cancer and having it spread to other parts of the body. For that reason these patients may also have a total cystectomy.

In select cases where the cancer cells have invaded deep into the bladder wall, but only in a limited part, a partial cystectomy can be done. This spares enough bladder so that the urine does not need to be diverted. Only 1 in 10 patients with advanced disease are candidates for partial cystectomy.

When doing a total cystectomy for cancer in women, the uterus, ovaries, fallopian tubes, part of the vagina, and urethra are usually removed. In men, the prostate gland and the seminal vesicles (which produce the semen) are usually removed. Some men may also have the urethra removed (note: not the penis, only lining of the urine channel that runs through the penis).

Urinary diversion after total cystectomy

Once the bladder is removed, the patient needs another way pass urine out of the body. This is known as urinary diversion and many options are available.

Ileal conduit or urostomy

The ureters can be rerouted or diverted to a tube made from a piece of the small intestine or ileal conduit. A piece of small intestine with its blood supply attached is separated from the main flow of the bowel contents. This piece is connected on one end to the ureters and on the other end to an opening made on the outside of the body, usually to the right and below the belly button. The opening created is called a stoma. A disposable bag is then attached over the opening on the outside of the body. Before leaving the hospital, the patient learns how to change the bag and how to clean and take care of the stoma.

Continent diversion or neobladder

A long piece of intestine, can also be used to construct a new bladder. Small intestine, or colon or both are used to construct neobladders.

In men in whom the urethra is still intact, the neobladder and urethra are reattached and the urinary system works much as it did before.

In all women and those men in whom the urethra needs to be removed, reattachment to the urethra is impossible. In these cases, the 'neobladder' is brought up to the abdomen with a special non-leaking valve so that urine does not leak out. This requires the patient to pass a small rubber tube into the neobladder every 4-6 hours to empty the stored urine.

Creating and putting in place a neobladder to the urethra provides more comfort and ease to the male patients than having a stoma, but the operation is somewhat riskier and can only be used for some patients. Creating and putting in place a neobladder to the abdomen provides more cosmetic appeal to the patient than having a stoma, but the operation is also riskier. Before the bladder is removed, the patient should discuss with the doctor what will be done to divert the urine and what effect it could have on the patient's lifestyle.

Chemotherapy
Intravesical chemotherapy

(Intra=into, vesical=bladder, chemo=chemical)

Intravesical chemotherapy refers to chemical treatments that are installed into the bladder through the urethra using a catheter or rubber tube. These procedures are usually done in the office and require only 5 minutes to perform. The tube is removed immediately, but the medications must be kept in the bladder for about two hours.

Most commonly, intravesical chemotherapy is used for patients whose tumors have been completely removed but who are at high risk of having recurrences or new tumors develop at a later time.

On occasion, intravesical chemotherapy is used to treat multiple bladder tumors that could not be completely removed by surgery.

Chemotherapy given directly into the bladder does not usually cause side effects like chemotherapy taken orally or injected into a muscle or vein. Because the therapy is limited to the bladder most of the side-effects are the irritative effects on the bladder, such as frequency, urgency and burning with urination. Most of these effects dissipate after the treatments are discontinued. The frequency and duration of treatments vary with different medications. Currently used drugs include names such as BCG, Thio-Tepa, Mitomycin-C, Adriamycin, Interferon. Each has unique properties and side effects which will be discussed by your Urologist before use.

Systemic chemotherapy

Systemic chemotherapy means that the medication is allowed to enter the blood stream, either by injection or by ingestion. These are medications that have the ability to kill cells that are multiplying quickly such as cancer cells. Many normal body cells also multiply quickly and can be harmed as well. Hopefully, the strong drugs used in systemic chemotherapy will cause more damage to cancer cells than to normal cells.

Some of the rapidly dividing cells systemic chemotherapy can harm include those of the bone marrow, hair and those lining the stomach. That is why systemic chemotherapy often causes anemia, bleeding, hair loss, nausea and vomiting, increased likelihood of developing infections and mouth sores. Most of these side effects disappear once treatment is stopped. Since each person reacts differently to treatment, the side effects will differ.

The doctor, usually a Medical Oncologist, must be very careful about how large the dose is and how often it is given.

Studies are now going on to see if giving systemic chemotherapy before or after removing the bladder (total cystectomy) could improve survival results. This idea is still being tested and the treatments are experimental only.

Radiation

The aim of radiation therapy is to destroy cancer cells by injuring their ability to divide, while causing the least amount of damage possible to other cells. Radiation may be used to help shrink bladder tumors before removal, to destroy any cancer cells remaining after surgery, and to relieve pain for patients not healthy enough to have surgery. It may also be used as the only treatment for patients not able to endure cystectomy and chemotherapy.

New studies suggest that combined radiation and chemotherapy might be better than cystectomy for some patients. Other studies are looking at the combined use of surgery, chemotherapy, and radiation to control tiny pockets of metastatic disease among patients with advanced bladder cancer. Both these approaches are still considered experimental.

Most radiation therapy given for bladder cancer is external beam, meaning the radiation is beamed from a source outside the body. Radiation can also be given off by radioactive pellets implanted inside the body through thin tubes.

Side effects of radiation include skin changes, nausea and vomiting, and a tired or sluggish feeling. These generally go away once treatment is stopped.

Support for the patient

Providing the best care for the patient means not only treating the cancer, but easing the side effects and all the physical and emotional strains. This calls for a teamwork approach among the surgeon, the doctors who will plan radiation and chemotherapy, the pharmacists, nurses, social workers, and other health care workers.

Dietitians can help patients make any needed dietary changes so that their nutritional needs are met during and after treatment. Nurses often provide emotional support and teach the patient and other members of the family "do's and don'ts" of home health care. Patients whose bladders had to be removed and who pass urine through a stoma can get help and advice on cleaning and taking care of the stoma from a stoma therapist.

Radical surgery and radiation can impair sexual function. A majority of men will be unable to have an erection after surgery. In some cases, where an attempt to spare the nerves to the penis is possible, the ability is recovered over time. If erections do not return satisfactorily, there are other means, such as implanting a prosthesis in the penis, that can restore sexual function. In men, because the prostate has been removed, no semen will be ejaculated and all men will be unable to father children. A women who has had part of her vagina removed may have it reconstructed using tissue from the intestine. For both men and women, any loss of sexual function can cause emotional distress and an understanding and supporting partner can help the patient through this difficult time.

Psychological counseling can help patients and family members to cope with the disease and its effects on their lives. Patients and family members may find it helpful to join a group offering emotional support and advice on coping with bladder cancer.

American Cancer Society programs that offer support to cancer patients include Can Surmount and I Can Cope. In addition, the American Cancer Society's Cancer Response System, a free telephone information service, can refer patients to other local resources. Patients and family members should stay actively involved in choosing the right treatment. They have a right to know everything about the treatment and should ask questions.

Follow-up care

Follow up depends on the stage and type of disease that is being treated.

For patients with superficial bladder cancers that are removed with telescopic surgery, urinalysis and cystoscopy should be done on a regular basis. Usually every three to four months for the first year and then less often, but at least once a year. Based on the results of cystoscopy and cytology, further tests may be ordered.

For patients after total cystectomy for advanced disease, frequent follow-up exams are needed to see if the disease has recurred or spread to other parts of the body. These exams should be done every three to six months during the first three years after treatment. Most bladder cancers that recur do so during the first three years. Patients whose bladders have been removed will be examined to see if the rest of the urinary system is disease free and if the urinary diversion is working properly.

Expected survival times

The outlook for patients for early-stage bladder cancer that has not invaded the bladder wall is very good. About 90% of those patients live for five or more years with localized diagnosis and treatment. For patients whose cancer has spread to areas near the bladder, the 5 year survival rate is 45%. For those with advanced disease that has spread far from the bladder, the 5-year survival rate is 10%.

How to help guard against bladder cancer

• Don't smoke. If you do, make plans to quit right away. If you need help in quitting, call the American Cancer Society.
• As part of your overall defense against cancer, have regular medical checkups.
• If you notice blood in your urine, or any other change in bladder habits, see your doctor.