Bladder Cancer

Illustration of the bladder. Source: SEER training site.

Bladder cancer is a disease in which cancer (malignant) cells form in the tissues of the bladder. It is the second most common malignancy of the genitourinary tract.

Other Names

• Carcinoma of the bladder
• Malignant neoplasm of the bladder

Types

Bladder cancer is classified based on the type of cells that become malignant:

• Urothelial (transitional cell) carcinoma: Cancer that originates in cells from the innermost tissue layer of the bladder. In the United States, approximately 90% of cases of bladder cancer are urothelial carcinomas.^[1]
• Squamous cell carcinoma: This originates from squamous cells, which are thin, flat cells that may form in the bladder after long-term infection or irritation from chronic catheter use. In the Middle East and parts of Africa, this is the most common type of bladder cancer, accounting for about 75%. In these regions, it is most commonly due to infection with a parasite called Schistosoma.^[1]
• Adenocarcinoma: Less than 2% of bladder cancers. This type of cancer begins in glandular (secretory) cells that may form in the bladder after long-term irritation and inflammation such as a bladder infection. This type of cancer is the most common type seen in individuals with certain disorders, such as bladder exstrophy.
• Small cell carcinoma: This is a rare form of bladder cancer that may coexist with other types of bladder cancer, such as urothelial carcinoma.
• Other tumor types, such as pheochromocytoma and lymphoma, can also occur in the bladder.

Cancer is also named by how deep it has spread into the bladder wall. Cancer that is confined to the lining of the bladder (urothelium) is sometimes called superficial bladder cancer. Because researchers don't agree on the definition of this term, however, it is more accurate to use the T stage to describe it. Ta tumors do not invade beyond the inner layer of the bladder. T1 tumors invade through the first layer, the lamina propria. T2 tumors have gone through the lining of the bladder and into the muscle. T3 and T4 tumors have spread outside of the bladder. T2 to T4 tumors are often called invasive bladder cancer.

Signs and Symptoms

The most common symptom of bladder cancer is blood in the urine (hematuria). Blood that is found on urinalysis only is called microscopic hematuria. One study of 292 patients with microscopic hematuria showed that 16 of them had tumors of the urinary tract.^[2] Patients who have gross hematuria, or blood that they see in their urine, have a higher chance of having bladder cancer than those with microscopic hematuria.

Other symptoms of a problem in the bladder follow. These symptoms are more commonly due to other conditions affecting the bladder, such as urinary tract infection.

• Frequent urination due to irritation of the bladder
• Inability to urinate
• Pain during urination
• Lower back pain
• Fatigue due to anemia from blood loss in the urine
• Bone pain due to spread of cancer to the bone

Causes

Bladder cancer is caused by mutations in the DNA of bladder cells that allows them to grow uncontrollably. Many risk factors make this occurrence more likely, such as smoking, exposure to certain chemicals, and diet.

Diagnosis

Tests that examine the urine, vagina, or rectum are used to help detect and diagnose bladder cancer.

Exams and tests

The following tests and procedures may be used:

• Urinalysis: A test to check the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells. It is also used to look for signs of infection. Red blood cells in the urine are the most common laboratory abnormality in bladder cancer.
• Physical exam: If the tumor is small and superficial within the bladder, no mass may be felt on examination. However, with invasive cancer, a large mass may be felt. In an exam of the vagina and/or rectum, the doctor inserts gloved fingers into the vagina and/or rectum to feel for a mass.
• CT scan (CAT scan): A radiologic procedure that takes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A CT scan can be used for many different organ systems, and some organs are best visualized with injections of contrast material. A substance may be injected into a vein or swallowed to help the organs or tissues show up more clearly. The main advantage of a CT scan is to distinguish cancer confined to the bladder from cancer that has moved into and through the bladder wall.
• Intravenous pyelogram (IVP): A series of x-rays of the kidneys, ureters, and bladder to find out if cancer is present in these organs. Contrast material is injected into a vein, and makes its way through to the kidneys, ureters, and bladder. X-rays are then taken to see the anatomy of these organs.
• Cystoscopy: The diagnosis and initial staging of the disease is done by cystoscopy. This is a procedure to look inside the bladder and urethra to check for abnormal areas along the bladder wall. A cystoscope is inserted through the urethra and into the bladder. A cystoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for evidence of cancer. Washings of the bladder may also be done and sent to the lab where cells in the urine and bladder wall are examined to look for cancerous cells.
• Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. A biopsy for bladder cancer is usually done during cystoscopy under anesthesia. It may be possible to remove the entire tumor during biopsy.
• Urine cytology: Examination of urine under a microscope to check for abnormal cells.

Staging

Once bladder cancer has been diagnosed, further tests are performed to determine the exact tumor location and whether it has spread within the bladder or beyond to other parts of the body.

The process used to determine the extent of the tumor is called staging. The staging of all cancers is important because it guides the treatment options that the doctor will use to treat the patient. When looking at how advanced the tumor is, the focus is whether the tumor is very superficial on the inner bladder wall, if it has extended beyond the muscular layer, or if it has extended beyond the bladder completely.

The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as masses or anything else suspicious. A history of the patient's health habits and past illnesses and treatments will also be taken.
• Cystoscopy: A procedure to look inside the bladder and urethra to check for abnormal areas. A cystoscope is inserted through the urethra into the bladder. A cystoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A contrast material may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.

Treatment

The treatment of bladder cancer depends on the stage.

Stage 0 (papillary carcinoma and carcinoma in situ)

In stage 0, abnormal cells are found in tissue lining the inside of the bladder. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is divided into stage 0a and stage 0is, depending on the type of the tumor:

• Stage 0a is also called papillary carcinoma, which may look like tiny mushrooms growing from the lining of the bladder.
• Stage 0is is also called carcinoma in situ, which is a flat tumor on the tissue lining the inside of the bladder.

Treatment of stage 0 may include the following:

• Transurethral resection with fulguration (burning of the tumor and its base)
• Transurethral resection with fulguration followed by intravesical biologic therapy or chemotherapy
• Segmental or radical cystectomy

Stage I

In stage I, cancer has formed and spread to the layer of tissue under the inner lining of the bladder.

Treatment of stage I bladder cancer may include the following:

• Transurethral resection with fulguration
• Transurethral resection with fulguration followed by intravesical biologic therapy or chemotherapy
• Segmental or radical cystectomy
• Radiation implants with or without external radiation therapy

Stage II

In stage II, cancer has spread to either the inner half or outer half of the muscle wall of the bladder.

Treatment of stage II bladder cancer may include the following:

• Radical cystectomy with or without surgery to remove pelvic lymph nodes
• Combination chemotherapy and radical cystectomy
• External radiation therapy combined with chemotherapy
• Radiation implants before or after external radiation therapy
• Transurethral resection with fulguration
• Segmental cystectomy

Stage III

In stage III, cancer has spread from the bladder to the fatty layer of tissue surrounding it, and may have spread to the reproductive organs (prostate, uterus, vagina).

Treatment of stage III bladder cancer may include the following:

• Radical cystectomy with or without surgery to remove pelvic lymph nodes
• Combination chemotherapy followed by radical cystectomy
• External radiation therapy combined with chemotherapy
• External radiation therapy with radiation implants
• Segmental cystectomy

Stage IV

In stage IV, cancer has spread from the bladder to the wall of the abdomen or pelvis. Cancer may have spread to one or more lymph nodes or to other parts of the body.

Treatment of stage IV bladder cancer may include the following:

• Radical cystectomy with surgery to remove pelvic lymph nodes
• External radiation therapy (may be as palliative therapy to relieve symptoms and improve quality of life)
• Urinary diversion as palliative therapy to relieve symptoms and improve quality of life
• Cystectomy as palliative therapy to relieve symptoms and improve quality of life
• Chemotherapy alone or after local treatment (surgery or radiation therapy)

Recurrent cancer

Recurrent bladder cancer is cancer that has come back after it has been treated. The cancer may return in the bladder or elsewhere in the body.

Treatment of recurrent bladder cancer depends on previous treatment and where the cancer has recurred. Treatment for recurrent bladder cancer may include the following:

• Surgery
• Chemotherapy
• Radiation therapy

Types of treatment

Different types of treatment are available for patients with bladder cancer. Some treatments are standard (the currently used treatment). Standard treatments include:

Surgery

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 (cauterize) the tumor away with high-energy electricity. This is known as fulguration.

This video shows the resection of a bladder tumor using a cystoscope.

• 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, or partial, 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 usually 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 may have already spread in the body. Treatment given after surgery, to increase the chances of a cure, is called adjuvant therapy.

Radiation 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 is 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

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.

Psychotherapy

Some studies have shown effects of psychotherapy on cancer, some have not. As yet, no specific studies have been done in bladder cancer. So far, we have no reasons to suggest that psychotherapy would be less useful in specific types of cancer. Spiegel and his collegues (1989) at Stanford university have seen double length of survival in women with breast cancer after group psychotherapy. These groups, initiated by Yalom, were directed at mutual support, emotional expression, and sharing and existential issues. Two studies by Goodwin (2001) and Kissane (2007)with oncologically less experienced therapists, did not see effects on survival, nor did Edelman (1999) using cognitive behavioral therapy (CBT). In colon cancer and other gastrointestinal cancers, positive effects of individual, peri-operative bedside psychotherapy were seen by Kuchler (2007). Fawzy and co-workers (1993) noticed longer disease-free periods in patients with melanoma after a course in problem-focused coping. Experiential, existential, and problem-focused counseling by oncologically experienced psychotherapsts may be a useful adjunct to treatment.

Biologic therapy

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.

Prevention

Raw broccoli is a rich source of isothiocyanates, which have been shown to prevent cancer. Source: FreeDigitalPhotos.net

An effective regimen for preventing bladder cancer is not yet known. Studies have suggested that megadose vitamins, vitamin A, vitamin B6, vitamin C, and vitamin E may be helpful for reducing the risk of bladder cancer or its recurrence. However, good quality studies are lacking.^[3]

Certain fruits and vegetables have also been associated with a lower risk of bladder cancer. These include cruciferous vegetables such as broccoli and cauliflower, leafy greens, apples, and citrus fruits.^[4] The effect of cruciferous vegetables is thought to be due to chemicals known as isothiocyanates, which are found in broccoli, cauliflower, and broccoli sprouts.^[5] Cooking destroys these compounds, however, so it is likely that the benefit will be strongest when raw vegetables are consumed.^[6]

Living with Bladder Cancer

Lifestyle changes

Patients with superficial bladder cancers have a high chance of recurrence (about 1/3). Usually, these recurrences are confined to the surface of the bladder and do not spread.^[7]

Quitting smoking has been shown to lower the chance of bladder cancer coming back.^[8][9]

Long-term care

Patients who have been diagnosed with non-invasive bladder cancer are advised to undergo cystoscopies on a regular basis to check whether the tumor has come back and treat it if it has.

Patients who undergo cystectomy (removal of the bladder) have a new means of emptying urine created. Depending on the type of urinary diversion, they will have to learn a new way of emptying and caring for their urinary tract.

Chances of Developing Bladder Cancer

Risk factors

Risk factors for bladder cancer include the following:

• Smoking^[10]
• Being exposed to certain substances at work^[11]
• Certain dietary patterns have been linked to an increased risk of bladder cancer. One study showed that the highest risk diet was one high in coffee, tea, and added sugar. Diets high in red meat, fried eggs, potatoes, and red wine also were associated with an increased risk of developing bladder cancer.^[12]
• Being older, male, or white
• Having an infection caused by Schistosoma, a parasite common in northern Africa

Genetics

Several genes have been found to be important in bladder cancer. One of these is p53, which is more commonly seen in patients with aggressive bladder cancer. Researchers have proposed that measuring the expression of this gene may allow physicians to better predict their patients' prognoses.^[13]

Heredity

A family history of bladder cancer increases the chance of developing it two-fold. However, most cases of bladder cancer are not thought to be hereditary. Certain families do have hereditary forms of bladder cancer, however.^[14]

Related Problems

Related disorders

A review of 476 patients who underwent removal of their bladders to treat bladder cancer showed that 4.6% of them later developed cancer of the kidney or ureters. Risk factors for this included more bladder tumors, involvement of the urethra in men, and the presence of carcinoma in situ.^[15]

Clinical Trials

New types of treatment are being tested in clinical trials. These include the following:

Chemoprevention

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

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. Fiberoptic 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.

Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available here.

Research

Multiple tumor markers are being studied for bladder cancer. Tumor markers may be used to diagnose cancer earlier, to better estimate a patient's prognosis, and to follow patients for cancer recurrence (and maybe avoiding the need for multiple cystoscopies).^[16]

Expected Outcome

Survival rates

Patients with carcinoma in situ who have a complete response to intravesical chemotherapy with bacillus Calmette-Guérin have approximately a 20% risk of disease progression at 5 years; patients with incomplete response have approximately a 95% risk of disease progression. Several treatment methods (i.e., transurethral surgery, intravesical medications, and cystectomy) have been used in the management of patients with superficial tumors, and each method can be associated with 5-year survival in 55%-80% of patients treated.^[17]

Patients who undergo cystectomy for bladder cancer that has not spread outside of the bladder have five-year survival rates of 75%-80%.^[18] Patients with more deeply invasive tumors, which are also usually less well differentiated, and those with lymphovascular invasion experience 5-year survival rates of 30%-50% following radical cystectomy. When the patient presents with locally extensive tumor that invades pelvic viscera or with metastases to lymph nodes or distant sites, 5-year survival is uncommon, but considerable symptomatic palliation can still be achieved.^[17]

Recovery time

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 age and general health of the patient.

History

Research conducted by Alan Yagoda in the 1970s and 1980s revolutioned the treatment of bladder cancer with chemotherapy. His discovery of the effectiveness of the MVAC regimen improved five-year bladder cancer survival rates from 10% to 66%.^[19]

Epidemiology

Incidence

In 2008, the National Cancer Institute estimates that there will be 68,810 new cases of bladder cancer and 14,100 deaths due to bladder cancer. About 70%-80% of patients with a new diagnosis of bladder cancer have superficial disease (Tis, Ta, or T1).^[17]

Public Health

The American Urologic Association has issued guidelines on the evaluation of patients who have microscopic hematuria (blood in the urine).^[20]

Other Resources

National Cancer Institute

• U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer any questions.
• The NCI's Live Help online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

References

1. ↑ ^{1.0 1.1} Johansson SL, Cohen SM. Epidemiology and etiology of bladder cancer. Semin Surg Oncol. 1997 Sep-Oct;13(5):291-8. Abstract
2. ↑ Mishriki SF, Nabi G, Cohen NP. Diagnosis of urologic malignancies in patients with asymptomatic dipstick hematuria: prospective study with 13 years' follow-up. Urology. 2008 Jan;71(1):13-6. Abstract
3. ↑ Busby JE, Kamat AM. Chemoprevention for bladder cancer. J Urol. 2006 Nov;176(5):1914-20. Abstract
4. ↑ Sacerdote C, Matullo G, Polidoro S, et al. Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder cancer. Mutagenesis. 2007 Jul;22(4):281-5. Epub 2007 May 21. Abstract
5. ↑ Munday R, Mhawech-Fauceglia P, Munday CM, et al. Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res. 2008 Mar 1;68(5):1593-600. Epub 2008 Feb 29. Abstract
6. ↑ Tang L, Zirpoli GR, Guru K, et al. Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):938-44. Abstract
7. ↑ Ozono S, Hinotsu S, Tabata S, et al; Nara Uro-Oncology Research Group. Treated natural history of superficial bladder cancer. Jpn J Clin Oncol. 2001 Nov;31(11):536-40. Abstract | Full Text
8. ↑ Chen CH, Shun CT, Huang KH, et al. Stopping smoking might reduce tumour recurrence in nonmuscle-invasive bladder cancer. BJU Int. 2007 Aug;100(2):281-6; discussion 286. Epub 2007 Apr 5. Abstract | Full Text
9. ↑ Fleshner N, Garland J, Moadel A, et al. Influence of smoking status on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the bladder. Cancer. 1999 Dec 1;86(11):2337-45. Abstract | Full Text
10. ↑ Alberg AJ, Kouzis A, Genkinger JM, et al. A prospective cohort study of bladder cancer risk in relation to active cigarette smoking and household exposure to secondhand cigarette smoke. Am J Epidemiol. 2007 Mar 15;165(6):660-6. Epub 2007 Jan 4. Abstract | Full Text
11. ↑ Bosetti C, Boffetta P, La Vecchia C. Occupational exposures to polycyclic aromatic hydrocarbons, and respiratory and urinary tract cancers: a quantitative review to 2005. Ann Oncol. 2007 Mar;18(3):431-46. Epub 2006 Aug 25. Abstract | Full Text
12. ↑ De Stefani E, Boffetta P, Ronco AL, Deneo-Pellegrini H, Acosta G, Mendilaharsu M. Dietary patterns and risk of bladder cancer: a factor analysis in Uruguay. Cancer Causes Control. 2008 Jul 1. [Epub ahead of print]. Abstract
13. ↑ George B, Datar RH, Wu L, Cai J, Patten N, Beil SJ, et al. p53 gene and protein status: the role of p53 alterations in predicting outcome in patients with bladder cancer. J Clin Oncol. 2007 Dec 1;25(34):5352-8. Abstract
14. ↑ Mueller CM, Caporaso N, Greene MH. Familial and genetic risk of transitional cell carcinoma of the urinary tract. Urol Oncol. 2008 Jun 16. [Epub ahead of print]. Abstract
15. ↑ Wang P, Luo JD, Wu WF, et al. Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy. Braz J Med Biol Res. 2007 Jul;40(7):979-84. Abstract | Full Text
16. ↑ Kim WJ, Bae SC. Molecular biomarkers in urothelial bladder cancer. Cancer Sci. 2008 Apr;99(4):646-52. Abstract
17. ↑ ^{17.0 17.1 17.2} National Cancer Institute Web site. Bladder Cancer Treatment.
18. ↑ Malkowicz SB, van Poppel H, Mickisch G, et al. Muscle-invasive urothelial carcinoma of the bladder. Urology. 2007 Jan;69(1 Suppl):3-16. Abstract
19. ↑ William P. Didusch Center for Urologic History. Chemotherapy.
20. ↑ American Family Physician Web site. Asymptomatic Microscopic Hematuria in Adults: Summary of the AUA Best Practice Policy Recommendations.

External Links

American Urological Association

• Patient Education Site

National Cancer Institute

• [1]HealthShare Groups Patient/Family Support