When cells that make up the bladder—the hollow organ that stores urine—begin to grow out of control, they can form a tumor. Most bladder cancers start in the innermost lining of the bladder (urothelium or transitional epithelium). As the cancer cells grow into or through the other layers in the bladder wall, it can be difficult to treat. Over time, the cancer may spread beyond the bladder to other parts of the body.

Symptoms can include:

• Blood in the urine (hematuria) is the most common symptom, often without pain
• Frequent and urgent need to urinate
• Pain during urination
• Pain in the lower abdomen
• Back pain

Urothelial carcinoma (also known as transitional cell carcinoma) is the most common type of bladder cancer. This cancer starts in the urothelial cells that line the inside of the bladder. Cancerous cells may also spread to other parts of the urinary tract that contain urothelial cells in their lining, including part of the kidneys, the ureters and urethra.

Squamous cell carcinoma makes up about one to two percent of all bladder cancers, but are almost always an invasive form of the disease.

Adenocarcinoma is a highly invasive form of bladder cancer that is only about one percent of all bladder cancers. These cancer cells have a lot in common with colon cancers.

Small cell carcinoma is extremely rare and makes up less than one percent of bladder cancers. They form in nerve-like cells called neuroendocrine cells and usually grow quickly.

Sarcoma cells form in the muscle cells of the bladder and are very rare.

Researchers are still not certain what causes bladder cancer, but there are several risk factors that can trigger the disease. Some of these risk factors—race, ethnicity, age, gender, family history or congenital birth defects—cannot be controlled. Caucasians, men, people over 55, people born with rare bladder birth defects and individuals with a family history of bladder cancer are at greater risk.

Still, there are many risk factors associated with bladder cancer that individuals can control.

• Smoking causes about half of all bladder cancers in men and women. Smokers are nearly three times more likely to be diagnosed with the disease than non-smokers.
   
• Exposure to industrial chemicals often used to make rubber, leather, textiles, paint and printing products increases the risk for bladder cancer.

• Certain medicines and herbal supplements including the diabetes medication pioglitazone (Actos) and dietary supplements containing aristolochic acid have been linked to an increased risk of urothelial cancers.
   
• Arsenic in drinking water boosts an individual’s risk of bladder cancer.
   
• Fluid consumption is linked to bladder cancer. People who drink a lot of fluids (especially water) have lower rates of bladder cancer. Emptying the bladder more often helps flush toxic chemicals from the bladder.

Bladder cancer is diagnosed using a variety of tools.

A medical history and physical exam assess overall general health and any risk factors. Sometimes, a bladder tumor can be felt during a physical exam.

Urinalysis checks for blood and other substances in a sample of urine.

Urine cytology looks for the presence of cancer and pre-cancer cells using a microscope.

Urine cultures determine if a bacterial infection might be causing symptoms rather than cancer.

Urine tumor marker tests confirm the presence of bladder cancer. One or more tests may be used, including NMP22 (also known as BladderChek), BTA Stat, Immunocyt  and UroVysion.

Cystoscopy offers a view inside the bladder via a long, thin tube with a light and a lens or a small video camera on the end. A fluorescence cystoscopy (blue light cystoscopy) may be done along with routine cystoscopy to fill the bladder with a light-activated drug that is absorbed by cancer cells. When the physician shines a blue light through the cystoscope, cancer cells will glow—allowing abnormal areas of the bladder to be visible.

Transurethral resection of bladder tumor (TURBT) collects biopsy samples of abnormal-looking bladder tissue spotted during a cystoscopy. This tissue is sent to a lab to be examined by a pathologist. During the procedure, the physician removes the tumor and some of the bladder muscle around the tumor. Samples from several different parts of the bladder may be collected, especially if cancer is suspected but a tumor isn’t visible.

Biopsy confirms the presence or absence of bladder cancer. If cancer is detected, the pathologist indicates whether it is non-invasive or invasive and determines the cancer’s grade. Non-invasive cancer is confined to the inner layers of cells. Invasive cancer has spread to the deeper layers of the bladder. Grade is assigned based on how the cancer cells look under a microscope.

• Low-grade cancers look more like normal bladder tissue. People with these cancers usually have a good prognosis.
   
• High-grade cancers look less like normal tissue. High-grade cancers are more likely to grow into the bladder wall and spread outside the bladder. These cancers can be harder to treat.

Imaging tests such as x-rays, magnetic resonance imaging (MRI), sound waves (ultrasound) and tests that use radioactive substances to create pictures of the inside of the body may all be used to determine if the cancer has spread to tissues and organs near the bladder, nearby lymph nodes or distant parts of the body.

After studying biopsy samples of the bladder tumor under a microscope, a pathologist determines the grade and stage of the tumor. Staging reveals how much of the tissue contains cancer. The stages of bladder cancer include:

T0 - there is no evidence of a primary tumor in the bladder

Ta - tumor is contained in the bladder lining and is not found in any layers of the bladder

Tis - carcinoma in situ (CIS) is a high-grade, but “flat” cancer

T1 - the tumor has invaded the bladder lining, into the second layer, but has not reached the muscle layer 

T2 - the tumor extends into the muscle layer of the bladder

T3 - the tumor extends beyond the muscle layer and into tissue surrounding the bladder—usually fat surrounding the bladder

T4 - the tumor has spread to other areas near the bladder such as the prostate in men or vagina in women