Carlos G. Arcangeli, MD & Mark A. Rosen, MD

Adult and Pediatric Urology

Bladder Cancer

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Female urinary tractIntroduction

Cancer of the bladder is the fourth most common cancer among men and the ninth most common cancer among women. About 39,500 men and 14,900 women will develop bladder cancer each year in the United States. Cancer of the bladder may occur at any age, but it usually strikes those over 50 years old. The most common cause of bladder cancer in the U.S. is cigarette smoking, but there are also certain chemicals in hair dyes, petroleum products, and others that may cause bladder cancer. If detected and treated early, bladder cancer is almost always cured (the 5-year survival rate of early bladder cancer is 90%). Unfortunately, bladder cancer that spreads to other parts of the body is a very serious cancer, and less than one in ten patients with metastatic bladder cancer survive five or more years . Each year about 6,000 men and 3,000 women will die of the disease. During the past 30 years, the death rate for bladder cancer has declined slightly due to earlier detection and better treatment.

What the bladder does

The bladder is a muscular sac that collects and stores urine. It is hollow and its shape depends on how much urine it holds. When it is empty it looks like a deflated balloon. As it fills, it becomes rounded and pushes up against the abdomen. Urine is made up of water and wastes removed from the blood by the kidneys. The urine then travels down tubes known as ureters and is stored in the bladder until it can be released from the body through the urethra. Cancer causing substances are excreted in the urine and come in contact with the cells that line the bladder.

The bladder is lined by special cells, called transitional cells. These cells are unique in that they have the ability to expand and deflate, which makes sense as the bladder fills and empties of urine. Almost all bladder cancers arise in this lining layer. Most bladder tumors form finger-like (called papillary) growths that project from the bladder lining into the inside of the bladder. Bladder tumors can be solitary or in multiple areas of the bladder at the same time. Some tumors are more solid growths, and these are more likely to be aggressive tumors that invade into the underlying bladder muscle. Occasionally bladder cancer presents as a flat, red area of cancer cells which start in the transitional cell lining of the bladder but don’t form a growth into the bladder lumen. This type of bladder cancer, called carcinoma-in-situ (CIS), is a serious type of bladder cancer. Cancers originating in the bladder muscle are very rare.

Superificial bladder tumors

Types of Bladder Cancer

The health risk posed by a bladder cancer and the recommended treatment options are determined by three factors: the cell type, the tumor grade, and the tumor stage.

Cell Type

Bladder cancers are classified according to the type of cell that has become cancerous. About 90% or more of cancers of the bladder involve transitional cells which line the bladder wall. Transitional cells are unique to the urinary tract and line the kidneys and ureters as well. Other types of cells that are found less frequently in bladder cancer include squamous cell cancers or adenocarcinomas.

Grade

The grade is defined by the pathologist from the bladder biopsy. The grade gives us an idea of how fast the cancer might be growing or how aggressive it might be. High grade cancers grow faster and spread earlier than low grade cancers. The current system of grading uses three different grades: well-differentiated, moderately differentiated, and poorly differentiated (or Grade I, II or III). Well-differentiated means the cancer has more resemblance to normal bladder tissue and therefore usually does not grow or spread quickly. Poorly differentiated tumors do not resemble normal bladder and usually grow quickly and spread to other tissues earlier. The tumor grade is a good indicator of the likelihood that tumors will come back in the bladder after they are initially removed.

Stage

Bladder cancer staging system

The tumor stage is the extent of the tumor within the bladder and whether or not it has spread to tissues around the bladder or to other parts of the body. The bladder has an inner lining of transitional cells, a layer of loose tissue and blood vessels under the lining called the lamina propria, and then bladder muscle, which squeezes to push out the urine. The most important factor is bladder tumor staging is whether the tumor invades into the bladder wall or simply grows from the lining of the bladder.

Stage Ta

Tumors that don’t invade at all are considered stage Ta, and these tumors are by far the most common form of bladder cancer. These tumors form a growth that projects into the bladder cavity, but the tumors do not invade into the bladder wall and do not spread. They can bleed or cause bothersome urinary symptoms, but they are usually not a serious medical problem. Most of these tumors can be treated simply by removing them through a telescope, and more invasive surgery or chemotherapy is usually not necessary. Most patients with superficial tumors will not go on to develop serious, invasive cancer, but two-thirds will have recurrence of tumor in the bladder during their lifetime. Patients with recurrent superficial tumors may require treatment with a medication placed into the bladder to prevent recurrence.

Stage T1

Stage T1 tumors invade into the middle layer of the bladder wall. These are serious tumors because they have a high chance of recurring as malignant cancers in the future. All patients with stage T1 tumors should undergo repeat biopsy to be sure that they don’t have an invasive, malignant cancer. If a second biopsy also show stage T1 patients should undergo treatment with a medication placed into the bladder (called BCG) to lower the risk of serious recurrence. Patients with stage T1 tumors require very close followup because they are at high risk of developing life-threatening cancer.

Carcinoma-in-situ (CIS)

Carcinoma-in-situ, or CIS, is an aggressive but early stage of bladder cancer. CIS sometimes causes blood in the urine, and sometimes it causes bothersome urinary frequency or incontinence. It looks like a flat red area on the bladder wall instead of a tumor, but it has a high risk of becoming a life-threatening cancer in the future. All patients with CIS should have bladder treatments with BCG to lower the risk of recurrence.

Invasive cancer

Tumors that invade into the muscle layer of the bladder or deeper (labeled T2a, T2b, T3,and T4 in the image above) are life-threatening, malignant cancers. They represent about 15% of bladder cancers and may require major surgery, chemotherapy, or radiation treatments.

Who is at risk of developing Bladder Cancer?

Bladder cancer was one of the first cancers for which carcinogens were found to play a role in causing the disease. Smokers are three times as likely to develop bladder cancer as nonsmokers. 3 of every 5 cases of bladder cancer is linked to smoking. Bladder cancer is more common in highly industrialized areas and among workers exposed to certain chemicals. Certain aniline derivatives, benzidine, 2-napthylamine, and other chemicals used in dye manufacturing increase the risk to workers involved in the process. Painters, hair stylists, and workers in the rubber, metal, textile, and leather industries are also at high risk. The artificial sweeteners saccharin and cyclamates have been shown to cause bladder cancer in animals when given in very large doses. The link between these sweeteners and bladder cancer in humans has not been shown. In the Middle East and Africa, certain parasitic worm infections have been linked with bladder cancer.

Signs and Symptoms of Bladder Cancer

Blood in the urine is usually the first sign of bladder cancer. Many times the amount of blood in the urine is so small that the patient will not see it but it is found by urinalysis done as part of a regular checkup or treatment for another medical condition. If blood can be seen in the urine, it may change the color of the urine from yellow to smoky to rusty to bright red. The bleeding may disappear for weeks or even months. Blood in the urine can be caused by a number of medical problems besides cancer, including infection, prostate enlargement,benign tumors, kidney stones and a number of kidney diseases. If blood is noticed, a doctor should be consulted to determine its cause. Early stage bladder cancer does not usually cause pain, but may cause frequent urination or incontinence.

How the diagnosis of bladder cancer is made

The diagnosis of bladder cancer begins with a complete medical history. The doctor will ask questions about the patient’s overall health and bladder cancer risk factors, such as smoking and exposure to certain industrial chemicals. To determine if cancer is present, some or all of the following tests may be done:

Urinalysis

Urinalysis is the analysis of the physical and chemical properties of a sample of urine. As part of the diagnostic workup for bladder cancer, it can reveal blood in the urine in amounts too small to be noticed by the patient, or can confirm that blood is still in the urine.

X-Rays

X-rays can help determine the source of the bleeding. The most common test is a CT scan of the abdomen, in which a small amount of special x-ray dye is injected into the bloodstream. This dye is quickly absorbed by the kidneys. A CT scan then takes images of the entire abdomen, including the kidneys and bladder. In some cases ultrasound may be used instead of a dye test.

Cystoscopy

Cystoscopy permits the doctor to actually look inside the bladder. A small slender telescope, called a cystoscope, is passed through the urethra into the bladder. The urologist can carefully examine the inner surface of the bladder and look for any abnormal areas. This is usually done in the doctor’s office using a local anesthetic (a jelly like substance with anesthetic in it). The procedure takes only a few minutes to perform.

Resection and Biopsy

Tumor resection and biopsy is the removal and examination under a microscope of suspicious looking areas from the bladder. The cells are removed with special cystoscopes that allow biopsy of tissue. These procedures are usually performed in the hospital with an anesthetic. Since bladder cancer may be present in more than one area of the bladder, several samples of bladder—from both normal and abnormal looking areas—may be removed for examination. Only a biopsy can tell for sure whether cancer is present. The biopsies from areas that do not have cancer ( called ‘random biopsies’) will often give valuable information about the long-term chances of cancer recurrence.

Cytology

Cytology is a test to look for cancer cells in the urine. Some of the lining cells of the bladder wash off in the urine and these cells are examined by a skilled pathologist to look for cancer cells. BTA TEST and NMP-22 are new urine tests that are able to indicate in many cases the presence of bladder cancer cells. The tests are done on a voided urine specimen and can be done quickly in the doctor’s office or laboratory. BTA and NMP-22 are able to detect unique proteins (or antigens) that many bladder cancers produce.

Bladder Cancer Treatment

The treatments for superficial bladder cancer and invasive cancers differ greatly. Superficial bladder tumors are usually treated with minor, outpatient surgery to remove the tumor, whereas invasive cancers are treated with surgery, chemotherapy, or both. Radiation and chemotherapy can increase the chances for curing invasive bladder cancer, help control metastatic disease, and prevent the disease from recurring, but they are usually not used as the main or only treatment. Click here to read more about bladder cancer treatments.

How to help guard against Bladder Cancer

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