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BLADDER CANCER OVERVIEW — Cancer of the urinary bladder is one of the most common cancers. The most common type of bladder cancer in the United States and western Europe is urothelial carcinoma, also known as transitional cell carcinoma (TCC). Other types of bladder cancer are also found occasionally, including squamous carcinoma and adenocarcinoma.
In other areas of the world, such as the Northern African and Mediterranean regions, squamous carcinoma may be seen more often in areas where schistosomiasis (a parasitic infection) is endemic, although urothelial cancer remains the most common bladder cancer there as well.
This topic will discuss the symptoms, diagnosis, and staging of urothelial cancer.
BLADDER CANCER RISK FACTORS — Bladder cancer is more common in males and older adults (the average age at diagnosis is 73 years). Other factors that may increase the risk of bladder cancer include [1]:
●Tobacco exposure – More than 50 percent of bladder cancers are caused by tobacco exposure including cigarettes, cigars, chewing tobacco, and likely e-cigarettes ("vaping") [2]. People who smoke cigarettes have a two- to fourfold increased risk of bladder cancer compared with never smokers, with long-term heavy smokers having a 6- to 10-fold increase in risk. Exposure to second-hand smoke also increases a person's risk [3,4].
●Chemical and environmental exposures – Being exposed to certain chemicals or industrial compounds in the workplace or the environment may significantly increase the risk of bladder cancer. Of particular risk are a type of dyes that include "azo" compounds. In most cases, it takes many years after the chemical exposure for the person to develop bladder cancer, although in many cases, direct causation is difficult to establish. Drinking water with high levels of arsenic or chlorinated trihalomethanes, a byproduct of drinking water disinfection, has been associated with bladder cancer. High levels and prolonged exposure to certain pesticides and fertilizers can also increase risk. Air pollution in residential areas close to oil refineries, which emit air pollutants such benzene and toluene, has also been associated with increased bladder cancer risk [5].
●Family history – A family history of bladder cancer (having a relative who has or had the disease) probably increases a person's risk of developing the cancer, especially in those who smoke cigarettes.
BLADDER CANCER SYMPTOMS — The initial signs and symptoms of bladder cancer are often mistaken for those of a urinary tract infection, enlarged prostate, or kidney stone. (See "Patient education: Urinary tract infections in adolescents and adults (Beyond the Basics)" and "Patient education: Kidney stones in adults (Beyond the Basics)".)
Symptoms often come and go, and are often not severe. The most common symptoms include the following:
Hematuria (blood in the urine) — The most common sign of bladder cancer is blood in the urine (hematuria). Hematuria caused by cancer is usually visible (turning the urine pink or red), intermittent, and not painful. However, people with microscopic hematuria (when blood is visible under a microscope but does not change the color of the urine) also may rarely have bladder cancer. (See "Patient education: Blood in the urine (hematuria) in adults (Beyond the Basics)".)
However, screening for blood in the urine is not recommended for the general population, because hematuria occurs commonly in people who do not have bladder cancer. In one study, only about 10 percent of people with visible hematuria and 2 to 5 percent of those with microscopic hematuria had bladder cancer [6,7].
Anyone with blood in their urine should be evaluated by a health care provider. The type of evaluation will depend on the person's age, sex, and risk factors for cancer [8]. Visible blood in the urine is most commonly associated with cancer, so people with this symptom (especially males who are smokers) should have a complete evaluation of the kidneys, ureters, bladder, and urethra. People who are found to have microscopic blood in their urine may require an evaluation but can also be observed if they are at low risk for cancer. (See 'Bladder cancer diagnosis' below.)
Pain — Pain may also be a sign of bladder cancer. Pain may develop in the flank (the sides of the mid-back), above the pubic bone, or in the perineum (the area between the genitals and anus). Pain in the flank region can develop when there is complete or partial blockage of the ureter (the tube connecting kidney to bladder) (figure 1) on that side, with the pain being due to back pressure of urine.
Pain can also occur during "voiding" (urinating); this is called dysuria.
Voiding symptoms — Although most people with bladder cancer do not have symptoms, some do have voiding (urinating) symptoms, such as needing to urinate frequently or urgently during the day or night and leaking urine on the way to the bathroom. However, most people with these symptoms do not have bladder cancer but another condition, such as overactive bladder, a urinary tract infection, or an enlarged prostate. (See "Patient education: Urinary tract infections in adolescents and adults (Beyond the Basics)" and "Patient education: Urinary incontinence in women (Beyond the Basics)".)
Other symptoms — Other symptoms of bladder cancer, such as fatigue, weight loss, and lack of appetite, usually are not present until the late (more advanced) stages of bladder cancer.
BLADDER CANCER DIAGNOSIS — Anyone who has signs or symptoms of bladder cancer should have a complete evaluation of the kidneys, ureters, bladder, and urethra, especially if they are over 50 years old. This evaluation includes one or more urine tests, cystourethroscopy (direct visual inspection of the urethra and bladder), and an imaging test of the kidneys and ureters.
Urine tests — Several urine tests may be recommended in people with bladder symptoms.
●Urinalysis is a test that uses a chemical dipstick that changes color in response to the presence of certain features in the urine, such as white blood cells, red blood cells, and glucose (sugar). The urine is also examined with a microscope.
●Urine cytology is a test in which an experienced pathologist examines a sample of urine with a microscope to see if there are abnormal-appearing cells shed from the lining of the bladder. A pathologist can often identify whether abnormal cells are actually cancerous.
Imaging tests — Imaging tests can help to detect any masses or abnormalities in the kidneys, ureters, bladder, or urethra. The optimal imaging test (computed tomography [CT] scan, magnetic resonance imaging [MRI], or kidney ultrasound) depends upon the individual situation.
●CT scan – CT scan is an imaging test that examines the structure of the kidneys, ureters, and bladder. The CT scan can show the extent of a cancer, determine if there is a blockage in the urinary tract, and determine if the cancer has spread outside the bladder. CT scans usually require the use of contrast dye.
There is a small risk of having an allergic reaction to the dye. People who are allergic to contrast dye, iodine, or shellfish should let the radiology specialist know of their allergy before the test. They might be pretreated before the dye is given to avoid a reaction, or it may be possible to have an alternate test.
●MRI – MRI of the kidney, ureters, and bladder may provide additional information in staging bladder cancer and can be used in people with allergies to contrast dye [9].
●Kidney ultrasound – This test is good for evaluating the kidneys but may miss cancers of the lining of the urinary tract or small kidney tumors. Kidney ultrasound avoids radiation and use of contrast materials. It is used to evaluate people with low risk for cancer who have microscopic blood in the urine [8].
Cystoscopy — Cystoscopy, also called cystourethroscopy, is a procedure that is done to examine the lining of the urethra and bladder. It can be done by a urologist in an office setting or in an operating room. When performed in the office, a numbing gel is applied to the urethra to decrease discomfort. A small tube with a camera (cystoscope) is then inserted into the bladder through the urethra.
Using the cystoscope, the physician examines the lining of the bladder and urethra. If abnormal tissue is seen, a biopsy can be taken. Biopsies may be done in the office or in the operating room. The biopsy specimen(s) is examined with a microscope to determine if cancerous cells are present.
People who are referred for a second opinion to a specialized bladder cancer center may need to have a repeat cystoscopy to characterize the tumor in more detail and to help in planning of treatment [10].
BLADDER CANCER STAGING AND GRADING — The treatment and prognosis of bladder cancer depend upon its stage, its grade, and the risk that the cancer will recur [11].
Staging — Bladder cancer staging is based upon how far the cancer has penetrated into the tissues of the bladder, whether the cancer involves lymph nodes near the bladder, and whether the cancer has spread beyond the bladder to other organs.
After the diagnosis of bladder cancer is confirmed, one or more tests may be performed to stage the disease. This may include a chest x-ray, and computed tomography (CT) scan or magnetic resonance image (MRI) of the pelvis.
The most commonly used system for staging is the TNM system (Tumor, Node, Metastasis) [12]. Combinations of the T, N, and M classifications are grouped together (stage groupings) to describe four stages of disease. The T stages are defined as follows:
●T0: No tumor is found in the bladder.
●Ta: The tumor is only found on the inner lining (mucosa) of the bladder.
●Tis: Carcinoma in situ is a noninvasive but high-grade and typically flat lesion.
●T1: The tumor has invaded the lamina propria (tissue under the lining of the bladder) but without involvement of muscle.
●T2: The tumor has grown into the muscle layer of the bladder, either superficially (stage T2a) or deeply (stage T2b). Stage 2 and higher tumors are considered to be muscle-invasive cancers.
●T3: The tumor has grown through the bladder muscle into the fat layer surrounding the bladder.
●T4: The tumor has spread to surrounding organs, such as the prostate, bowel, vagina, or uterus.
Grading — A cancer's grade refers to how the cancer cells appear under the microscope. Grade is one factor used to predict how likely the cancer is to recur after treatment and, ultimately, the person's chance of surviving his or her cancer. Bladder tumors are classified as either low or high grade. Low-grade cancers can recur but rarely invade. High-grade cancers are more likely to recur and become invasive.
In noninvasive tumors, the grade may be low or high, while almost all invasive cancers (tumor stage T1 and greater) are high grade.
Risk grouping (low, intermediate, or high risk) — Several factors are used to describe a bladder cancer as low, intermediate, or high risk based upon the likelihood of cancer recurrence and progressions. These factors include the size, number, and appearance of the tumor(s), if it recurs, and how deeply it invades into the bladder. These risk groupings impact the type of treatment used by clinicians.
A person whose cancer is low risk may be able to have less aggressive treatment and follow-up, whereas a person with higher-risk bladder cancer may require more aggressive treatment and more frequent follow-up.
BLADDER CANCER TREATMENT — The treatment of bladder cancer is discussed separately. (See "Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)" and "Patient education: Bladder cancer treatment; muscle invasive cancer (Beyond the Basics)".)
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Bladder cancer (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Urinary tract infections in adolescents and adults (Beyond the Basics)
Patient education: Kidney stones in adults (Beyond the Basics)
Patient education: Blood in the urine (hematuria) in adults (Beyond the Basics)
Patient education: Urinary incontinence in women (Beyond the Basics)
Patient education: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)
Patient education: Bladder cancer treatment; muscle invasive cancer (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Chemoprevention of urothelial carcinoma of the bladder
Clinical presentation, diagnosis, and staging of bladder cancer
Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder
Etiology and evaluation of hematuria in adults
Non-urothelial bladder cancer
Pathology of bladder neoplasms
Radical cystectomy
Screening for bladder cancer
Treatment of primary non-muscle invasive urothelial bladder cancer
Urinary diversion and reconstruction following cystectomy
The following organizations also provide reliable health information.
●National Cancer Institute
(www.cancer.gov/types/bladder)
●The National Library of Medicine
(medlineplus.gov/bladdercancer.html)
●American Society of Clinical Oncology
●American Cancer Society
