About bladder cancer

What is bladder cancer?

What is the bladder?

The urinary bladder, or the bladder, is a hollow organ in the pelvis. Most of it lies behind the pubic bone of the pelvis, but when full of urine, it can extend up into the lower part of the abdomen. Its primary function is to store urine that drains into it from the kidney through tube-like structures called the ureters. The ureters from both the kidneys open into the urinary bladder. The bladder forms a low-pressure reservoir that gradually stretches out as urine fills into it. In males, the prostate gland is located adjacent to the base of the bladder where urethra joins the bladder. From time to time, the muscular wall of the bladder contracts to expel urine through the urinary passage (urethra) into the outside world. The normal volume of the full bladder is about 400 ml-600 ml, or about 2 cups.

What are the layers of the bladder?

The bladder consists of three layers of tissue. The innermost layer of the bladder, which comes into contact with the urine stored inside the bladder, is called the "mucosa" and consists of several layers of specialized cells called "transitional cells," which are almost exclusively found in the urinary system of the body. These same cells also form the inner lining of the ureters, kidneys, and a part of the urethra. These cells form a waterproof lining within these organs to prevent the urine from going into the deeper tissue layers.

The middle layer is a thin lining known as the "lamina propria" and forms the boundary between the inner "mucosa" and the outer muscular layer. This layer has a network of blood vessels and nerves and is an important landmark in terms of the staging of bladder cancer (described in detail below in the bladder cancer staging section).

The outer layer of the bladder comprises of the "detrusor" muscle and is called the "muscularis." This is the thickest layer of the bladder wall. Its main function is to relax slowly as the bladder fills up to provide low-pressure urine storage and then to contract to compress the bladder and expel the urine out during the act of passing urine. Outside these three layers is a variable amount of fat that lines and protects the bladder like a soft cushion and separates it from the surrounding organs such as the rectum and the muscles and bones of the pelvis.

Picture of the urinary system: kidneys, ureters, and bladder

What is bladder cancer?

Bladder cancer is an uncontrolled abnormal growth and multiplication of cells in the urinary bladder, which have broken free from the normal mechanisms that keep uncontrolled cell growth in check. Bladder cancer (like cancers of other organs) has the ability to spread (metastasize) to other body parts, including the lungs, bones, and liver.

Bladder cancer invariably starts from the innermost layer of the bladder (for example, the mucosa) and may invade into the deeper layers as it grows. Alternately, it may remain confined to the mucosa for a prolonged period of time. Visually, it may appear in various forms. Most common is a shrub-like appearance (papillary), but it may also appear as a nodule, an irregular solid growth or a flat, barely perceptible thickening of the inner bladder wall (see details in subsequent sections).

What is the burden of bladder cancer in the U.S.?

Bladder cancer has the dubious distinction of inclusion on the top 10 list of cancers, with an estimated 74,690 new cases occurring in 2013-2014 within the U.S. Bladder cancer is three to four times more likely to be diagnosed in men than in women and about two times higher in white men than in African-American men. Bladder cancer killed an estimated 15,210 people in 2013. In the U.S., the lifetime bladder cancer risk for men is about one in 26 and for women about one in 90.

What are the types of bladder cancer?

Bladder cancer is classified on the basis of the appearance of its cells under the microscope (histological type). The type of bladder cancer has implications in selecting the appropriate treatment for the disease. For example, certain types may not respond to radiation and chemotherapy as well as others. The extent of surgery required for maximizing the chances of cure may also be impacted by the histological type of the cancer. In addition, bladder cancers are often described based on their position in the wall of the bladder. Noninvasive bladder cancers are located in the inner layer of cells (transitional cell epithelium) but have not penetrated into deeper layers. Invasive cancers penetrate into the deeper layers such as the muscle layer. Invasive cancers are more difficult to treat.

The more common types of bladder cancer and their relative incidence are given below:

  • Urothelial carcinoma (previously known as "transitional cell carcinoma") is the most common type and comprises 90%-95% of all bladder cancers. This type of cancer has two subtypes, papillary carcinoma (growing finger-like projections into the bladder lumen) and flat carcinomas that do not produce fingerlike projections. Urothelial carcinoma (transitional cell carcinoma) is strongly associated with cigarette smoking.
  • Adenocarcinoma of the bladder comprises about 1%-2% of all bladder cancers and is associated with prolonged inflammation and irritation. Most adenocarcinomas of the bladder are invasive.
  • Squamous cell carcinoma comprises 1%-2% of bladder cancers and is also associated with prolonged infection, inflammation, and irritation such as that associated with longstanding stones in the bladder. In certain parts of the Middle East and Africa (for example, Egypt), this is the predominant form of bladder cancer and is associated with chronic infection caused by Schistosoma worm (a blood fluke, that causes schistosomiasis, also termed bilharzia or snail fever).
  • Other rare forms of bladder cancer include small cell cancer (in bladder nerves), pheochromocytoma (rare), and sarcoma (in muscle tissue).



What are the symptoms for bladder cancer?

Bladder cancer signs and symptoms may include:

If you have hematuria, your urine may appear bright red or cola colored. Sometimes, urine may not look any different, but Blood in urine may be detected during a microscopic exam of the urine.

People with bladder cancer might also experience:

  • Back pain
  • Frequent urination

But, these symptoms often occur because of something other than bladder cancer.

When to see a doctor

If you have blood in your urine (hematuria), make an appointment with your doctor to get it checked out. Also make an appointment with your doctor if you have other signs or symptoms that worry you.



What are the causes for bladder cancer?

Bladder cancer develops when cells in the bladder begin to grow abnormally. Rather than grow and divide in an orderly way, these cells develop mutations that cause them to grow out of control and not die. These abnormal cells form a tumor.

Causes of bladder cancer include:

  • Smoking and other tobacco use
  • Exposure to chemicals, especially working in a job that requires exposure to chemicals
  • Past radiation exposure
  • Chronic irritation of the lining of the bladder
  • Parasitic infections, especially in people who are from or have traveled to certain areas outside the United States

It's not always clear what causes bladder cancer, and some people with bladder cancer have no obvious risk factors.

Types of bladder cancer

Different types of cells in your bladder can become cancerous. The type of bladder cell where cancer begins determines the type of bladder cancer. The type of bladder cancer determines which treatments may work best for you.

Types of bladder cancer include:

  • Urothelial carcinoma. Urothelial carcinoma, previously called transitional cell carcinoma, occurs in the cells that line the inside of the bladder. Urothelial cells expand when your bladder is full and contract when your bladder is empty. These same cells line the inside of the ureters and the urethra, and tumors can form in those places as well. Urothelial carcinoma is the most common type of bladder cancer in the United States.
  • Squamous cell carcinoma. Squamous cell carcinoma is associated with chronic irritation of the bladder, for instance from an infection or from long-term use of a urinary catheter. Squamous cell bladder cancer is rare in the United States. It's more common in parts of the world where a certain parasitic infection (schistosomiasis) is a common cause of bladder infections.
  • Adenocarcinoma. Adenocarcinoma begins in cells that make up mucus-secreting glands in the bladder. Adenocarcinoma of the bladder is rare in the United States.

Some bladder cancers include more than one type of cell.



What are the treatments for bladder cancer?

About 50% of all bladder cancers may be caused by cigarette smoking. The longer and heavier the exposure, greater are the chances of developing bladder cancer. The toxic chemicals in cigarette smoke, many of which are known cancer-causing substances (carcinogens), travel in the bloodstream after being absorbed from the lungs and get filtered into the urine by the kidneys. They then come in contact with the cells in the inner lining of the urinary system, including the bladder, and cause changes within these cells that make them more prone to developing into cancer cells. Quitting smoking decreases the risk of developing bladder cancer but takes many years to reach the level of people who have never smoked. However, as time passes after the quit date, the risk progressively decreases. In view of the above, it is extremely important for patients with bladder cancer to stop smoking completely since the chances of the cancer coming back after treatment are higher in those people who continue to smoke.

People who smoke also have a higher risk of many other types of cancer, including leukemia and cancers of the lung, lip, mouth, larynx, esophagus, stomach, and pancreas. Smokers also have a higher risk of diseases like heart attacks, peripheral vascular disease, diabetes, stroke, bone loss (osteoporosis), emphysema, and bronchitis.

Age and family history are other risk factors as is male sex. About 90% of people with bladder cancer are over age 55, though in exceptional cases the disease may surface in the third or fourth decade of life. Men are more prone to developing bladder cancer probably due to a higher incidence of smoking and exposure to toxic chemicals. A close relative with a history of bladder cancer may increase the predisposition for the development of this disease.

Exposure to toxic chemicals such as arsenic, phenols, aniline dyes, and arylamines increase the risk of bladder cancer. Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest risk. Recently, the drug pioglitazone (Actos), used to treat type 2 diabetes, has been suspected to increase a person’s risk to develop bladder cancer.

Radiation therapy (such as that for prostate or cervical cancer) and chemotherapy with cyclophosphamide (Cytoxan) has been shown to increase the risk for development of bladder cancer. Moreover, it may also delay the diagnosis of bladder cancer in patients presenting with symptoms of bleeding in urine since this bleeding may be incorrectly attributed by the patient and/or the physician to the bladder irritation caused by the chemotherapy or radiation (radiation cystitis).

Learn more about: Cytoxan

Long-term chronic infections of the bladder, irritation due to stones or foreign bodies, and infections with the blood fluke prevalent in certain regions of the world (as mentioned earlier) are some other factors which predispose to bladder cancer.



What are the risk factors for bladder cancer?

Factors that may increase bladder cancer risk include:

  • Smoking. Smoking cigarettes, cigars or pipes may increase the risk of bladder cancer by causing harmful chemicals to accumulate in the urine. When you smoke, your body processes the chemicals in the smoke and excretes some of them in your urine. These harmful chemicals may damage the lining of your bladder, which can increase your risk of cancer.
  • Increasing age. Bladder cancer risk increases as you age. Bladder cancer can occur at any age, but it's rarely found in people younger than 40.
  • Being white. White people have a greater risk of bladder cancer than do people of other races.
  • Being a man. Men are more likely to develop bladder cancer than women are.
  • Exposure to certain chemicals. Your kidneys play a key role in filtering harmful chemicals from your bloodstream and moving them into your bladder. Because of this, it's thought that being around certain chemicals may increase the risk of bladder cancer. Chemicals linked to bladder cancer risk include arsenic and chemicals used in the manufacture of dyes, rubber, leather, textiles and paint products.
  • Previous cancer treatment. Treatment with the anti-cancer drug cyclophosphamide increases the risk of bladder cancer. People who received radiation treatments aimed at the pelvis for a previous cancer have an elevated risk of developing bladder cancer.
  • Chronic bladder inflammation. Chronic or repeated urinary infections or inflammations (cystitis), such as might happen with long-term use of a urinary catheter, may increase the risk of a squamous cell bladder cancer. In some areas of the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis.
  • Personal or family history of cancer. If you've had bladder cancer, you're more likely to get it again. If one of your first-degree relatives — a parent, sibling or child — has a history of bladder cancer, you may have an increased risk of the disease, although it's rare for bladder cancer to run in families. A family history of hereditary nonpolyposis colorectal cancer, also called Lynch syndrome, can increase the risk of cancer in the urinary system, as well as in the colon, uterus, ovaries and other organs.



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