Bladder cancer is highly treatable, especially when detected early. Approaches to bladder cancer treatment include chemotherapy, biological therapy, radiation therapy and a number of options for bladder cancer surgery. The best treatment is determined by the individual and the nature of his or her cancer.
Epidemiology is the characterization of a disease as it affects populations. It identifies those who may be susceptible and the risk factors that influence the disease’s occurrence. The incidence has already been noted. Risk factors include age, race, gender, family medical history, personal medical history, environmental factors and smoking. Of all these, smoking poses the greatest risk for bladder cancer.
Age is a factor. The cancer is relatively rare in people under age 40 (less than 1% of cancers) but appears more frequently in those 60 and older. Most bladder cancers are diagnosed in people in their late 60s. Whites are 1.5 times more likely to develop the cancer than other races. Asians are at the least risk. Men are more than twice as likely as women to develop bladder cancer. People whose families have a history of bladder cancer are at greater risk. These people do not inherit bladder cancer. Rather they inherit a certain susceptibility to the disease.
Chronic urinary infection, kidney and bladder stones, and chronic bladder infections tend to raise the risk of bladder cancer. Environmental factors, such as arsenic in drinking water, and chemicals involved in specific occupations increase risks. The cancer is seen more frequently in hairdressers, machinists, printers, painters, truck drivers and people who work in rubber, chemical, textile, metal and leather industries. The Chinese herb Aristolochia fangchi contained in some diet pills has been tied to both kidney failure and bladder cancers.
Smoking creates the greatest risk for bladder cancer. The National Cancer Institute estimates that smoking may be responsible for 48% of bladder cancer deaths among men and 28% of such deaths among women.
The urinary tract consists of two kidneys, two ureters which drain urine from the kidneys into the bladder for storage, and the urethra which drains the bladder. The bladder is surrounded by lymph nodes, small specialized organs which feed cells with immune system functions into the blood stream. In women, the uterus lies just behind the bladder. In men, the prostate lies at the base of the bladder.
All these organs can be affected by bladder cancer and some of the therapy and surgery employed to treat it. The bladder wall is made of four layers: the inner layer (mucosa), a basement membrane or layer of connective tissue (lamina propria), a wall of muscle (detrusor muscle), and an outer layer of perivesical fat (serosa).
Age is a factor. The cancer is relatively rare in people under age 40 (less than 1% of cancers) but appears more frequently in those 60 and older. Most bladder cancers are diagnosed in people in their late 60s. Whites are 1.5 times more likely to develop the cancer than other races. Asians are at the least risk. Men are more than twice as likely as women to develop bladder cancer. People whose families have a history of bladder cancer are at greater risk. These people do not inherit the cancer. Rather they inherit a certain susceptibility to the disease.
Chronic urinary infection, kidney and bladder stones, and chronic bladder infections tend to raise the risk of bladder cancer. Environmental factors, such as arsenic in drinking water, and chemicals involved in specific occupations increase risks. The cancer is seen more frequently in hairdressers, machinists, printers, painters, truck drivers and people who work in rubber, chemical, textile, metal and leather industries.
Smoking creates the greatest risk. The National Cancer Institute estimates that smoking may be responsible for 48% of bladder cancer deaths among men and 28% of such deaths among women.
A diagnosis of bladder cancer begins with a discussion of the patient’s medical history. This is followed by a physical exam in which the doctor will feel the abdomen and pelvis for any physical signs bladder cancer tumors. The doctor may also include a rectal or vaginal exam. Study of a urine sample will determine if blood or cancer cells are present. In some cases the doctor will order an intravenous pyelogram. A harmless dye is injected into a vessel. The dye collects temporarily and improves the quality of the x-rays that follow.
Other imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) may be employed. Cytoscopy is common. This involves threading a thin tube through the urethra into the bladder. Miniaturized fiber optics provide light to allow the doctor to examine the bladder from within the cavity. Other miniaturized technology in the tube allows him to gather minute bladder tissue samples that will be sent to a pathologist who will study them for the presence of cancer cells.
Blue Light Technology in Bladder Cancer Therapy
Cleveland Clinic is among the first centers in the United States to use a new technology called Cysview that allows doctors to clearly see cancerous growths in the bladder. The Cysview system is an extension of traditional cystoscopy, in which a thin, tube-like telescope called a cystoscope is carefully passed up the urethra (the tube through which urine leaves your body) and into the bladder.
Cystoscopy lets the doctor inspect your bladder lining closely for any abnormal growths or suspicious areas, which can be removed for further examination using tiny surgical tools passed through the scope. Cysview blue light cystoscopy uses a fluorescent dye to highlight growths when the patient is placed under a special light. During the procedure, the bladder is examined in white and blue light. Cysview accumulates in the tumor cells and glows pink under blue light. The tumor cells are highlighted and stand out against normal bladder tissue, which keeps its blue appearance.
Types of Bladder Cancer
Bladder cancers are characterized by type, stage and grade. This characterization will help determine the therapy that is most likely to be successful.
Transitional cell (urothelial) carcinoma
Transitional cell (urothelial) carcinoma has its origins in the transitional cells that line the bladder. These cells are also found in kidneys, ureters, and the urethra. About 90 percent of bladder cancers are transitional cell carcinoma.
Squamous cell carcinoma
Squamous cell carcinoma begins in thin flat cells that can be found throughout the body including the bladder. About 6 to 8 percent of bladder cancers are squamous cell cancers. Adenocarcinoma- Adenocarcinoma begins in glandular cells in other body organs and spreads to the bladder. Adenocarcinomas account for about 2% of bladder cancers.
Bladder tumors may take different forms. Superficial urothelial tumors may or may not be invasive. They seldom spread deeply into the bladder wall. Papillary urothelial tumors are slender projections resembling the arm of a cactus that grow from the bladder wall toward the center of the bladder. Those that grow only toward the center are called noninvasive papillary urothelial tumors. Papillomas are benign (non-threatening) urothelial tumors, the removal of which can usually be accommodated by simple surgical procedures such as transurethral resection of the bladder (TURB). These tumors can recur in the bladder or elsewhere in the urinary tract.
Patients who have experienced the removal of papillomas undergo re-examinations at regular intervals to check for recurrence. Papillary urothelial carcinoma is an abnormal papillary tumor. Its cells have irregular sizes, shapes and arrangements. When these abnormalities are slight, the tumor is called "low grade." They seldom invade the bladder wall but often return following removal. The risk of bladder wall invasion is greater when cells in these tumors show greater abnormal characteristics. Flat urothelial tumors (carcinoma in situ or CIS) affect only the cells in the interior bladder lining. In the great majority of instances, these cancers are limited to the lining. When they invade the muscle layer they are called flat invasive urothelial carcinomas.
Stage refers to the extent of the cancer. There are several staging systems. The most commonly used is the TNM system in which T stands for tumor, N stands for lymph node involvement and M stands for metastases or the spread of cancer cells to locations distant from the bladder. A more general staging system rates cancers as Stage 0 through Roman numeral IV. See Table.
Thus, a tumor graded as T2aN0M0 would indicate a tumor that reaches from the inner mucosa layer through the connective tissue and up to half way into the muscle wall but shows no evidence of lymph node involvement or metastases.
Pathologists "grade" the cancer according to nature of the cancer cells within the tissue samples they have received from biopsies. There are three grades: low grade or well-differentiated cells; middle-grade or moderately differentiated cells, and high-grade or poorly differentiated cells. These three categories are represented by the Roman numerals I, II, III. Low grade cells (Grade I) may vary in size but most look relatively normal. Only a few of these cells will be multiplying within a tissue sample. Middle grade (Grade II) are more uneven in both appearance and size. An increased ratio of these cells will be multiplying in a tissue sample. High grade cells (Grade III) comprise the most aggressive form of bladder cancer. They are distorted, vary greatly in size, and a significant number will be multiplying.
There are four primary categories of bladder cancer treatment: chemotherapy, intravesical therapy, radiation therapy (radiotherapy), and surgery. Sometimes these are applied as a sole therapy and sometimes combinations of therapies will be used. The proper course of bladder cancer treatment is determined only after careful characterization of bladder cancer and consultation between the patient and his or her physician.
When considering bladder cancer treatment, a variety of factors come into play, including the nature of the cancer, the age and health of the patient, other conditions that may exist, and patient preference of bladder cancer treatment following patient education. Often other specialists will be called in to consult on the treatment. This insures that the treatment that is eventually determined is tailored to the patient and his or her cancer.
In general, superficial tumors of the bladder lining are treated with surgery and/or medical therapy. Invasive tumors that have penetrated one or more of the bladder’s walls require surgery that removes a portion or all of the bladder. Medical therapy and/or radiation treatments may be applied. The bladder is usually not removed when a cancer metastasizes. Chemotherapy is the standard treatment for metastatic bladder cancer.
Chemotherapy - Chemotherapy drugs take advantage of cancer cells’ propensity to grow faster than other cells. Since they are growing, they greedily absorb nutrients. During bladder cancer treatment, cancer cells also absorb anti-cancer drugs at a much higher rate than normal cells. This is how chemotherapeutic agents destroy cancer while leaving normal cells unharmed. Chemotherapeutic agents are administered intravenously, sometimes as sole agents, sometimes in combination, and sometimes in tandem with the administration of one therapy followed by another in a few days or weeks. Because the agents are administered intravenously, they reach all parts of the body and can have strong side-effects. Chemotherapy is usually indicated in patients with Stage IV bladder cancers and frequently as follow-up therapeutic treatment in Stage III surgical patients as a means to prevent recurrence.
The most commonly used agents are methotrexate, vinblastine, doxorubicin, cyclophosphamide, paclitaxel, carboplatin, cisplatin, ifosfamide and gemcitabine. These drugs are often used in combinations. The combination of gemcitabine and cisplatin has been shown to have fewer side effects than the MVAC regimen (methotrexate, vinblastine, doxorubicin and cisplatin) and is perhaps more frequently used. A paclitaxel-carboplatin is also frequently used. All these agents produce some degree of side effects in the course of bladder cancer treatment.
Selection of a bladder cancer treatment regimen depends on the nature of the cancer and the health of the patient, i.e. whether he or she has other diseases or conditions. The most effective regimen is given priority. Then side effects are considered. Side effects include tiredness, nausea and vomiting, diarrhea or constipation, hair loss, susceptibility to infections, and oral responses such as mouth ulcers, sore mouth and changes in sense of taste. Many of these side effects can be moderated or eliminated by other drugs.
Intravesical therapy - Intravesical therapy is the introduction of chemotherapeutic agents or biological agents (immunotherapy) in a fluid directly into the bladder through a catheter (flexible tube) threaded through the ureter. The process reduces or eliminates many of the side effects seen with intravenous therapy. Biological therapy or immunotherapy is the intravesical administration of a special non-infectious strain of the Bacillus Calmette-Guerin bacteria. It is not known in great detail how the virus works against cancer. It does not appear to attack cancer cells directly but rather produces a response from the immune system that targets and destroys cancer cells specifically.
Radiation - Radiation, like chemotherapy, takes advantage of cancer’s cells propensity to grow rapidly. The cancer cells’ constantly changing status makes them exceedingly susceptible to radiation treatment which destroys their DNA but leaves normal cells relatively unharmed. New imaging technologies allow tumors to be identified with improved clarity and computer-guided, focused radiation delivery systems minimize radiation exposure to adjacent organs and tissues.
Surgical Options - As with the other therapies, the nature of the bladder cancer surgery depends on the nature of the cancer. People with Stage 0 or Stage I disease are most often treated with transurethral resection of the bladder (TURB). The procedure is performed under general or spinal anesthesia. A thin tube is inserted through the urethra. Miniaturized fiber optics and miniaturized surgical instruments are threaded through the tube to remove cancerous tissue.
Partial cystectomy - Removal of only a portion of the bladder is a viable option when a tumor is invasive but all evidence indicates that it is a solitary tumor limited to a defined region of the bladder. The procedure reduces the size of the bladder but preserves a significant portion. Partial cystectomies may be accompanied by radiation and chemotherapy treatment. It is possible to increase bladder volume by incorporating tissue taken from another location, usually the intestine. Since the tissue is derived from the patient, there is seldom concern about tissue rejection.
The National Cancer Institute reports that an increasing number of urologists are supporting the concept of bladder preservation. Patient undergoing this conservative approach have done well and are not excluded from undergoing complete removal of the bladder (radical cystectomy) should the cancer recur at a later date.
Robotic Radical Cystectomy: A New Frontier in Treatment of Bladder Cancer
Radical cystectomy - This procedure involves complete removal of the bladder. An incision is made in the abdomen and the bladder and adjacent organs are carefully examined to determine the status of the cancer and see if it may have spread to adjacent structures and organs. The bladder is removed along with any other organs that may be affected.
Reconstructive procedures - Several options are available to the patient who has lost a bladder. In a procedure called urostomy, a segment of intestine is removed and reattached to the ureters. This leads urine from the kidneys an opening (stoma) near the belly button. A light, leak proof bag is attached to the stoma to collect urine. The bag can be emptied as needed.
A segment of intestine can also be formed into a small pouch or a larger "neobladder." The pouch or bladder is placed in the cavity left by the bladder and stores urine. A conduit, again made from intestine, leads to a stoma in the abdomen but in this instance a valve allows the pouch to be drained whenever he or she wishes. No bags are involved. The neobladder may be attached to the urethra to allow urine to be drained normally. The application of these procedures is dependant upon a number of factors. They are not available to all patients but these bladder cancer treatments can be successfully implemented in many.
Treatment option overview
There are different types of treatment for patients with bladder cancer.
Different types of treatment are available for patients with bladder cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.
Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.
Four types of standard treatment are used:
One of the following types of surgery may be done:
Transurethral resection (TUR) with fulguration: Surgery in which a cystoscope (a thin lighted tube) is inserted into the bladder through the urethra. A tool with a small wire loop on the end is then used to remove the cancer or to burn the tumor away with high-energy electricity. This is known as fulguration.
Radical cystectomy: Surgery to remove the bladder and any lymph nodes and nearby organs that contain cancer. This surgery may be done when the bladder cancer invades the muscle wall, or when superficial cancer involves a large part of the bladder. In men, the nearby organs that are removed are the prostate and the seminal vesicles. In women, the uterus, the ovaries, and part of the vagina are removed. Sometimes, when the cancer has spread outside the bladder and cannot be completely removed, surgery to remove only the bladder may be done to reduce urinary symptoms caused by the cancer. When the bladder must be removed, the surgeon creates another way for urine to leave the body.
Segmental cystectomy: Surgery to remove part of the bladder. This surgery may be done for patients who have a low-grade tumor that has invaded the wall of the bladder but is limited to one area of the bladder. Because only a part of the bladder is removed, patients are able to urinate normally after recovering from this surgery.
Urinary diversion: Surgery to make a new way for the body to store and pass urine.
Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy after surgery to kill any cancer cells that are left. Treatment given after surgery, to increase the chances of a cure, is called adjuvant therapy.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Bladder cancer may be treated with intravesical (into the bladder through a tube inserted into the urethra) chemotherapy. The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
New types of treatment are being tested in clinical trials. These include the following:
Chemoprevention is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or to reduce the risk that cancer will recur (come back).
Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiber optic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue.