Overview of Bladder Cancer
Medically reviewed by Dr. C.H. Weaver M.D. updated 9/2018
Bladder cancer is the fourth most common new cancer in men and the tenth in women. About 70,000 individuals will be diagnosed with bladder cancer this year.
The bladder is a hollow organ in the lower abdomen. Its primary function is to store urine, the waste that is produced when the kidneys filter the blood. Urine passes from the two kidneys into the bladder through two tubes called ureters and urine leaves the bladder through another tube called the urethra. The bladder has a muscular wall that allows it to get larger and smaller as urine is stored or emptied.
The wall of the bladder is lined with several layers of cells called transitional cells. Cancer arising from these cells makes up more than 90% of all bladder cancers and these are referred to as transitional cell carcinomas. Because transitional cell carcinomas are the most common type of bladder cancer, the information in this section only addresses treatment of transitional cell cancer of the bladder.(1,2,3)
Symptoms & Signs of Bladder Cancer
The most common sign of bladder cancer is hematuria or blood in the urine, which will turn the urine rust or red in color. Other signs and symptoms of bladder cancer may include pain during urination and frequent urination. Most patients with bladder cancer do not have symptoms other than hematuria. Unfortunately, most bladder cancers are not diagnosed until they have become very large. As a result, research is ongoing in order to develop urine tests that would enable earlier detection of bladder cancer when it is small and more easily treated. There are several promising tests under evaluation, but currently none are reliable enough for routine use.(1,2,3)
People with bladder cancer may experience the following symptoms or signs. Sometimes however individuals with bladder cancer may not have any of these changes
- Hematuria -blood in the urine
- Pain or burning sensation during urination
- Frequent urination
- Urgency to urinate many times throughout the night
- Feeling the need to urinate, but not being able to pass urine
- Lower back pain on one side of the body
Having these symptoms does not necessarily mean a person has bladder cancer. Infections, benign tumors, bladder stones, or other problems also can cause these symptoms. Anyone with these symptoms should see a doctor so that the problem can be caught early.(1,2)
Cause of Bladder Cancer
Bladder cancer occurs predominantly in elderly men and less frequently in women and younger men. Many bladder cancers are thought to be caused by exposure to cancer-causing agents that pass through the urine and come into contact with the bladder lining. The most important risk factor for bladder cancer is smoking, which increases risk by at least four-fold.(1,2)
Risk Factors for Bladder Cancer
A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will.
Although most bladder cancers develop sporadically, which means for no known reason the following factors may raise a person’s risk for developing bladder cancer:(1,2,3)
Age: The chance of getting bladder cancer increases with age. Bladder cancer affects primarily people in their sixties and seventies. People younger than 40 rarely get this disease, but it does happen occasionally.
Cigarette smoking: Cigarette smoking is directly responsible for most cases of bladder cancer, causing about half of all bladder cancer deaths in men and about one-third of those in women.
Working in certain industries: Some workers have a higher risk of getting bladder cancer because of carcinogens (cancer-causing agents) in the workplace. Workers in the rubber, dye, chemical, and leather industries are at increased risk as are hairdressers, machinists, metal workers, printers, painters, textile workers, and truck drivers.
Race: Whites get bladder cancer twice as often as African Americans and Latinos. The lowest rates are among Asians.
Gender: Men are three times more likely than women to develop bladder cancer. Women are more likely to die from the disease, however, because they are often not diagnosed in the early stage.
Pioglitazone (Actos) use: People who have taken the diabetes drug pioglitazone for more than 1 year may have a higher risk of developing bladder cancer.
Prior history of bladder cancer: People who have already had bladder cancer once are more likely to develop bladder cancer again.
Schistosomiasis: Individuals infected with this parasite are more likely to develop squamous cell bladder cancer.
Lynch syndrome: People with hereditary nonpolyposis colorectal cancer or HNPCC appear to be at increased risk of developing bladder cancer.
Arsenic exposure: Arsenic when found in drinking water has been associated with an increased risk of bladder cancer.(1,2)
Family history: People with family members who have bladder cancer are more likely to get the disease. Researchers are studying changes in certain genes that may increase the risk of bladder cancer.
Radiation Exposure: The use of radiation therapy for treating uterine cancer is associated with an increased risk of developing and dying from bladder cancer.4
Some risk factors, such as a genetic mutation within a gene called the p53 gene, are associated with a poor outcome following treatment with chemotherapy and/or radiation therapy. Therefore, physicians may look for the presence of such risk factors upon a diagnosis of bladder cancer in order to best plan a treatment regimen. Research is ongoing to identify risk factors that are associated with a poor outcome, as well as factors that indicate that some patients may require less treatment. By identifying such factors, physicians are better able to tailor treatment to meet the needs of individual patients.
Diagnosis & Tests for Bladder Cancer
If a patient has symptoms that suggest bladder cancer, the doctor will perform an evaluation that includes a complete physical exam and some lab tests. The physical exam may include a rectal or vaginal exam. In addition an outpatient procedure called a cystoscopy is usually used to diagnose bladder cancer. During a cystoscopy, the physician (a urologist) inserts a thin, lighted tube (cystoscope) into the bladder through the urethra to examine the internal lining of the bladder. The doctor can remove samples of tissue from the bladder with the cystoscope. A pathologist then examines the tissue under a microscope. The removal of tissue to look for cancer cells is called a biopsy. A biopsy is the only sure way to tell whether cancer is present. For a small number of patients, the doctor removes the entire cancerous area during the biopsy. For these patients, bladder cancer is diagnosed and treated in a single procedure.
When bladder cancer is diagnosed, the urologist will want to learn the stage or extent of the cancer, as well as the grade (aggressiveness) of the cancer as determined by its appearance under the microscope. Grade is important because it indicates how closely the cancer resembles normal tissue and suggests how fast the cancer is likely to grow. Low-grade cancers more closely resemble normal tissue and are likely to grow and spread more slowly than high-grade cancers.
Precision Medicine & Personalized Bladder Cancer Care
The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision medicines are being developed for the treatment of cervical cancer and patients should ask their doctor about whether testing is appropriate.
Staging of Bladder Cancer
When diagnosed with bladder cancer further tests are necessary to determine the extent of spread (stage) of the cancer. Cancer’s stage is a key factor in determining the best treatment. The stage of bladder cancer may be determined at the time of diagnosis or it may be necessary to perform additional tests.
Imaging tests: Tests such as X-rays, CT scans, magnetic resonance imaging (MRI) and positron emission tomography (PET) are used to help determine the stage and whether the cancer has spread beyond the bladder.
- Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
- Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
- Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
Intravenous pyelogram: (IVP) is a procedure which involves the injection of dye (contrast) into the blood. When the contrast travels through the kidneys and ureters, it allows these organs to be visualized with X-rays (fluoroscopy).
Urine tests: The laboratory checks the urine for blood, cancer cells, and other signs of disease. The most common urine test for bladder cancer is a urine cytology, similar to a Pap test.
Cystoscopy: The doctor uses a thin, lighted tube called a cystoscope to look directly into the bladder. The doctor inserts the cystoscope through the urethra to examine the lining of the bladder. The patient may need anesthesia for this procedure.
Stages of Bladder Cancer
Determining the stage and genomic profile of the cancer determines what treatment options exist. Cancers confined to the inner lining of the bladder are called “superficial” and comprise 70-80% of all bladder cancers. Cancers that have spread into the bladder wall are called “deep” bladder cancers and those that have spread to lymph nodes and/or distantly to lungs, liver or other organs are referred to as “metastatic.”(1,2)
Stage 0 (T0): Patients with stage 0 bladder cancer have the earliest stage of cancer that involves only the innermost layers of cells in the bladder. Depending upon the appearance of the cells under the microscope, stage 0 transitional bladder cancer is pathologically classified as either noninvasive papillary carcinoma or carcinoma in situ (CIS), both of which are considered to be “superficial” bladder cancers.
Stage I (T1): Patients with stage I bladder cancer have cancer that invades beneath the surface of the bladder into connective tissue, but does not invade the muscle of the bladder and has not spread to lymph nodes. This is also classified as a “superficial bladder cancer.”
Stage II (T2): Patients with stage II bladder cancer have cancer that invades through the connective tissue into the muscle wall, but has not spread outside the bladder wall or to local lymph nodes. Patients with cancer invading the inner half of the muscle of the bladder wall have a better outcome than patients with invasion into the deep muscle (outer half of the muscle of the bladder wall). Stage II bladder cancer is classified as a “deep” or “invasive” bladder cancer.
Stage III (T3): Patients with stage III bladder cancer have cancer that invades through the connective tissue and muscle and into the immediate tissue outside the bladder and/or invades the prostate gland in males or the uterus and/or vagina in females. With stage III bladder cancer, there is no spread to lymph nodes or distant sites. Stage III bladder cancer is also classified as a “deep” or “invasive” bladder cancer.
Stage IV (T4): Patients with stage IV bladder cancer have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall and/or has lymph node involvement and/or spread to distant sites. Stage IV bladder cancer is also referred to as “metastatic” bladder cancer. Recurrent Bladder Cancer: Patients with recurrent bladder cancer have cancer that has returned following initial treatment with surgery, radiation, chemotherapy or immunotherapy.
Recurrent: Patients with recurrent bladder cancer have cancer that has returned following initial treatment with surgery, radiation, chemotherapy or immunotherapy.
Screening/Prevention of Bladder Cancer
Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person´s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity or Genetic Factors
At this time, researchers have not identified any genetic factors that contribute to the development of bladder cancer.
- Family history. People with family members who have bladder cancer are more likely to get the disease. Researchers are studying changes in certain genes that may increase the risk of bladder cancer.
Environmental or Non-Genetic Factors
- Age. The chance of getting bladder cancer increases with age. Bladder cancer affects primarily people in their sixties and seventies. People younger than 40 rarely get this disease, but it does happen occasionally.
- Certain Diabetes Medications: A class of diabetes drugs called thiazolidinediones (TZDs) may increase the risk of bladder cancer.
- Cigarette smoking. Cigarette smoking is directly responsible for most cases of bladder cancer, causing about half of all bladder cancer deaths in men and about one-third of those in women.
- Working in certain industries. Some workers have a higher risk of getting bladder cancer because of carcinogens (cancer-causing agents) in the workplace. Workers in the rubber, dye, chemical, and leather industries are at increased risk as are hairdressers, machinists, metal workers, printers, painters, textile workers, and truck drivers.
- Race. Whites get bladder cancer twice as often as African Americans and Latinos. The lowest rates are among Asians.
- Gender. Men are three times more likely than women to develop bladder cancer. Women are more likely to die from the disease, however, because they are often not diagnosed in the early stage.
Screening and Early Detection
There is currently no standard screening test for bladder cancer. The following tests however may be used for screening for a recurrence in individuals with a history of bladder cancer
- Urine cytology
- Urine test for hematuria (blood in the urine)
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for developing that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type.
 National Cancer Institute. Bladder and Other Urothelial Cancers (PDQ®): Screening. Health Professional Version. Available at:http://www.cancer.gov/cancertopics/pdq/screening/bladder/HealthProfessional(Accessed May 5, 2008).
 Pashos CL, Botteman MF, Laskin BL, Redaelli A. Bladder Cancer: Epidemiology, Diagnosis, and Management. Cancer Practice 2002;10:311-322.
 National Cancer Institute. Bladder Cancer (PDQ®): Treatment. Health Professional Version. Available
 Baack Kukreja JE, Scosyrev E, Brasacchio RA, et al: Bladder cancer incidence and mortality in patients treated with radiation for uterine cancer. BJU International. Published early online. DOI: 10.1111/bju.12543