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 (which resembles skin cancer under the microscope) and adenocarcinoma (which has a glandular pattern, similar to bowel cancer, under the microscope).

In other areas of the world, such as the Northern African and Mediterranean regions, squamous carcinoma is seen more often, although urothelial cancers (or TCC) remain the most common tumors there as well.

This topic will discuss the symptoms, diagnosis, and staging of transitional cell carcinoma.

BLADDER CANCER RISK FACTORS

Bladder cancer is more common in men and in those who are older (the median age at diagnosis is 69 years). Other factors that may increase the risk of bladder cancer include:

• Exposure to chemicals — Being exposed to certain chemicals or industrial compounds in the workplace or the environment can 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.
• Cigarette smoke — People who smoke cigarettes have a two to four-fold increased risk of bladder cancer compared to never smokers, with long-term heavy smokers having a six to ten-fold increase in risk. Exposure to second-hand smoke also increases the risk [1,2].
• Family history — A family history of bladder cancer 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 or kidney stone. (See "Patient information: Urinary tract infections in adolescents and adults (Beyond the Basics)" and "Patient information: Kidney stones in adults (Beyond the Basics)".)

Symptoms often come and go and are 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 does not cause pain. However, people with microscopic hematuria (when blood is visible with a microscope but does not change the color of the urine) also may rarely have bladder cancer. (See "Patient information: Blood in the urine (hematuria) in adults (Beyond the Basics)".)

However, 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 [3,4].

Anyone who is over 40 years old who has visible blood in the urine should have a complete evaluation of the kidneys, ureters, bladder, and urethra. (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 space between the vagina or penis and rectum). 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 patients are asymptomatic, voiding symptoms, such as needing to urinate frequently or urgently during the day or night and leaking urine on the way to the bathroom, are seen in some people with bladder cancer. 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 information: Urinary tract infections in adolescents and adults (Beyond the Basics)" and "Patient information: Urinary incontinence in women (Beyond the Basics)".)

Others symptoms — Other symptoms of bladder cancer, such as fatigue, weight loss, and lack of appetite are not usually present until the late 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 the person is greater than 40 years old. This evaluation includes one or more urine tests, cystourethroscopy, 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 (IVP, CT scan, or kidney ultrasound) depends upon the individual situation.

• IVP — In an IVP (intravenous pyelogram), a radiopaque dye (one that is seen on x-ray) is injected into a vein. The dye collects in and is excreted by the kidneys. As the dye passes through the kidney and into the bladder, the urinary tract and any masses are visible on x-ray.
  
  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. You may be pre-treated before an IVP to avoid having an allergic reaction or may have an alternate test.
• CT scan — Computed tomography, or CT scan, is an imaging test that examines the structure of the kidneys, ureters, and bladder. The CT 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.

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 abnormal or cancerous cells are present.

Patients who are referred for a second opinion to a specialized bladder cancer center may have a repeat cystoscopy to characterize the tumor in more detail and to help in planning of treatment [5].

BLADDER CANCER STAGING AND GRADING

The treatment and prognosis of bladder cancer depend upon its stage, grade, and risk that the cancer will recur.

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 CT scan or magnetic resonance image (MRI) of the pelvis.

The most commonly used system for staging is the TNM system (tumor, node, metastasis) [6]. Combinations of the T, N, and M classifications are grouped together (stage groupings) to describe four stages of disease. The tumor (T) stages are defined as follows:

• T0: No tumor is found in the bladder.
• Ta: The tumor is only found on the inner lining of the bladder.
• T1: the tumor has invaded the lamina propria (tissue under the lining of the bladder)
• 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 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.

In noninvasive tumors, the grade may be low or high, while almost all invasive cancers (tumor stage T1 and greater) are high grade.

Low risk versus high risk — Several factors are used to describe a bladder cancer as low risk or high risk, based upon the likelihood of cancer recurrence. These factors include the size, number, and appearance of the tumor(s), if it recurs, and how deeply it invades into the bladder.

A person whose cancer is low risk may be able to have less aggressive treatment and follow up, whereas a person with high 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 information: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)" and "Patient information: Bladder cancer treatment; 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 information: 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 information: Urinary tract infections in adolescents and adults (Beyond the Basics)
Patient information: Kidney stones in adults (Beyond the Basics)
Patient information: Blood in the urine (hematuria) in adults (Beyond the Basics)
Patient information: Urinary incontinence in women (Beyond the Basics)
Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer (Beyond the Basics)
Patient information: Bladder cancer treatment; 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.

Adjuvant chemotherapy for muscle invasive urothelial (transitional cell) carcinoma of the bladder
Chemoprevention of bladder cancer
Clinical presentation, diagnosis, and staging of bladder cancer
Epidemiology and etiology of urothelial (transitional cell) carcinoma of the bladder
Etiology and evaluation of hematuria in adults
Experimental systemic therapy of metastatic bladder cancer
Laparoscopic/robotic-assisted radical cystectomy
Neoadjuvant treatment and bladder preservation options for muscle-invasive urothelial (transitional cell) bladder cancer
Nonurothelial bladder cancer
Pathology of bladder neoplasms
Radical cystectomy and bladder-sparing treatments for urothelial (transitional cell) bladder cancer
Screening for bladder cancer
Treatment of non-muscle-invasive bladder cancer
Urinary diversion and reconstruction following cystectomy

The following organizations also provide reliable health information.

• National Cancer Institute

     (www.cancer.gov/cancertopics/types/bladder)

• The National Library of Medicine

     (www.nlm.nih.gov/medlineplus/bladdercancer.html)

• American Society of Clinical Oncology

     (www.cancer.net/portal/site/patient)

• American Cancer Society

     (www.cancer.org/Cancer/BladderCancer/DetailedGuide/bladder-cancer-risk-factors)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

     (http://cancer.about.com/forum)

• The Bladder Cancer Advocacy Network

(http://www.bcan.org/)

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