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bladder-cancer

Bladder Cancer

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What is Bladder Cancer?

The bladder is an expandable, hollow organ in the pelvis that stores urine (the body’s liquid waste) before it leaves the body during urination. The urinary tract is made up of the kidneys, ureters, bladder, and urethra and is lined with a layer of cells called the urothelium. This layer of cells is separated from the muscularis propria (bladder muscles) by the lamina propria (a thin, fibrous band).

 Bladder cancer begins when normal cells in the bladder lining, most commonly urothelial cells, change and grow uncontrollably, forming a mass called a tumor. A tumor can be benign (noncancerous) or malignant (cancerous, meaning is can spread to other parts of the body).

Types of bladder cancer

First, the type of bladder cancer depends on the type of cell where the cancer begins:

Urothelial carcinoma. Urothelial carcinoma accounts for about 90% of all bladder cancers and begins in the urothelium. Urothelial carcinoma is the common term for this type of bladder cancer. It was previously called transitional cell carcinoma or TCC.

Squamous cell carcinoma. This type accounts for about 4% of all bladder cancers and starts in squamous cells, which are thin, flat cells that form part of the bladder lining.

Adenocarcinoma. This type accounts for about 2% of all bladder cancers and begins in glandular cells.

There are other, less common cell types that can develop into bladder cancer, including sarcoma (which begins in the fat or muscle layers of the bladder) and small cell anaplastic cancer (a rare type of bladder cancer that is likely to spread to other parts of the body).

In addition to its cell type, bladder cancer may be described as noninvasive, non-muscle-invasive, or muscle-invasive.

Noninvasive. This type of bladder cancer usually does not extend through the lamina propria, while both types of invasive cancer can extend through the lamina propria. Noninvasive cancer may also be called superficial cancer, although that term is being used less often because it may incorrectly imply that this type of cancer is not serious. Noninvasive bladder cancer is less likely to spread and can often be managed with surgery to remove tumors and chemotherapy placed in the bladder .

Non-muscle-invasive. Non-muscle-invasive bladder cancer typically grows only into the lamina propria. It is called invasive, but it is not the deeply invasive type that can spread to the muscle layer.

Muscle-invasive. Muscle-invasive bladder cancer spreads into the bladder's muscularis propria and sometimes to the fatty layers or surrounding tissue outside the muscle.

It is important to note that both noninvasive and non-muscle-invasive bladder cancers have the possibility of spreading into the bladder muscle or to other parts of the body. Additionally, all cell types of bladder cancer can metastasize (spread) beyond the bladder. If the tumor has spread into the surrounding organs (the uterus and vagina in women, the prostate in men, and/or nearby muscles), it is called locally advanced disease. Bladder cancer also often spreads to the lymph nodes in the pelvis. If it has spread into the liver, bones, lungs, lymph nodes outside the pelvis, or other parts of the body, the cancer is called metastatic disease. This will be outlined more in Staging.

Symptoms & Signs

People with bladder cancer may experience the following symptoms or signs. Sometimes, people with bladder cancer do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. Bladder cancer usually does not cause symptoms that specifically indicate cancer. Most often, bladder cancer is diagnosed when a person tells his or her doctor about blood in the urine, also called hematuria. Gross hematuria means that enough blood is present in the urine to be visible to the patient. It is also possible there are small amounts of blood in the urine unable to be seen; this is called microscopic hematuria, and it can only be detected with a urine test.

General urine tests are not used to make a specific diagnosis of bladder cancer because hematuria can be a sign of several other conditions that are not cancer, such as an infection or kidney stones. One type of urine test that can indicate the presence of cancer is cytology, a test in which the urine is studied under a microscope to look for cancer cells.

If you are concerned about a symptom or sign on this list, please talk with your doctor.    

Hematuria

Pain during urination

Frequent urination

Feeling the need to urinate many times throughout the night

Feeling the need to urinate, but not being able to pass urine

Lower back pain on one side of the body

Symptoms of advanced bladder cancer may include pain, unexplained appetite loss, and weight loss.

Sometimes when the first symptoms of bladder cancer appear, the cancer has already spread to another part of the body. In this situation, the symptoms depend on where the cancer has spread. For example, cancer that has spread to the lungs may cause a cough or shortness of breath, spread to the liver may cause abdominal pain or jaundice (yellowing of the skin and whites of the eyes), and spread to the bone may cause bone pain or a bone break.

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Risk Factors

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The following factors may raise a person’s risk of developing bladder cancer:

Tobacco use. The most common risk factor is cigarette smoking, although smoking cigars and pipes can also raise the risk of developing bladder cancer. Smokers are four to seven times more likely to develop bladder cancer than nonsmokers. 

Age. The likelihood of being diagnosed with bladder cancer increases with age. More than 70% of people with bladder cancer are older than 65 years old.

Gender. Men are three to four times more likely to develop bladder cancer than women, but women are more likely to die from bladder cancer than men. Before smoking rates for women increased, men were five to six times more likely to develop bladder cancer than women.

Race. White people are more than twice as likely to be diagnosed with bladder cancer as black people, but black people are twice as likely to die from the disease.

Chemicals. Chemicals used in textile, rubber, leather, dye, paint, or print industries; some naturally occurring chemicals; and chemicals called aromatic amines can increase the risk of bladder cancer.

Chronic bladder problems. Bladder stones and infections may increase the risk of bladder cancer. Bladder cancer may be more common for people who are paralyzed from the waist down and have had many urinary infections.

Cyclophosphamide (Cytoxan, Clafen, Neosar) use. People who have taken the chemotherapy drug cyclophosphamide have a higher risk of developing bladder cancer.

Pioglitazone hydrochloride (Actos) use. Recently, the U.S. Food and Drug Administration warned that people who have taken the diabetes drug pioglitazone hydrochloride for more than one year may have a higher risk of developing bladder cancer.  

Personal history. People who have already had bladder cancer once are more likely to develop bladder cancer again.

Fluid intake. People who do not regularly drink enough liquids may have a higher risk of bladder cancer. 

Schistosomiasis. People who have some forms of this parasitic disease (found particularly in parts of Africa and the Mediterranean region) are more likely to develop bladder cancer.

Arsenic. Arsenic is a naturally-occurring substance that can cause health problems if consumed in large amounts. In drinking water, it has been associated with an increased risk of bladder cancer. The chance of being exposed to arsenic depends on where you live and whether you get your water from a well or from a system that meets the standards for acceptable arsenic levels.

Diagnosis

Doctors use many tests to diagnose cancer and find out if it has metastasized. Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. A biopsy is the removal of a small amount of tissue for examination under a microscope. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Type of symptoms

Previous test results

The earlier bladder cancer is found, the better the chance for successful treatment. However, there is not yet a test that is accurate enough to screen the general population for bladder cancer, so most people are diagnosed with bladder cancer once they have symptoms. As a result, some patients have later stage disease when the cancer is first found, although most people diagnosed have noninvasive bladder cancer.

The following tests may be used to diagnose and learn more about the extent of bladder cancer:

Urine tests. The doctor tests a urine sample to find out if it contains tumor cells. If a patient is undergoing a cystoscopy (see below), an additional test may be performed that involves rinsing the bladder and collecting the liquid through the cystoscope or through another small tube that is inserted into the urethra. The sample can be tested in a variety of ways. The most common way is to look at the cells under a microscope, called urinary cytology. Urine passed out of the body during normal urination can also be examined by cytology. There are other urine tests using molecular analysis that can be done to help find cancer, usually at the same time as urinary cytology.

Cystoscopy and TURBT. This is the key diagnostic procedure for this disease. It allows the doctor to see inside the body with a thin, lighted, flexible tube called a cystoscope. Flexible cystoscopy is performed in the doctor's office and does not require an anesthetic (medication that blocks the awareness of pain). This short procedure can detect growths in the bladder and determine the need for a biopsy or surgery.

If abnormal tissue is found, the doctor will do a biopsy. This procedure is called a transurethral bladder tumor resection or TURBT. During a TURBT, the doctor can remove the tumor and a sample of the bladder muscle near the tumor. A TURBT is used to diagnose bladder cancer and find out how deeply it has grown into the layers of the bladder. After the TURBT is done, the urologist will also evaluate the bladder to see if any masses can be felt. This is called an exam under anesthesia or EUA. The sample removed during the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). A TURBT is also a treatment for a non-muscle-invasive tumor. 

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows abnormalities or tumors. Sometimes, a contrast medium (special dye) is injected into a patient’s vein to provide better detail. The patient should tell the staff giving this test beforehand if he or she is allergic to iodine or other contrast mediums.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium may be injected into a patient’s vein to create a clearer picture.

Stages and Grades

Staging is a way of describing where the cancer is located, if or where it has invaded or spread, and whether it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

For bladder cancer, the stage is determined based on the results of the sample removed during a TURBT  and whether the cancer has spread to other parts of the body, which is determined by imaging tests, a physical examination, and laboratory tests.

       

One tool doctors use to describe the stage is the TNM system. This system judges three factors: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to other parts of the body. The results are combined to determine the stage of cancer for each person. There are five stages of bladder cancer: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

   How large is the primary tumor and how deeply has it invaded the tissue? (Tumor, T)

   Has the tumor spread to the lymph nodes? (Node, N)

   Has the cancer metastasized to other parts of the body? (Metastasis, M)

Tumor. Using the TNM system, the "T" plus a letter and/or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. If there is more than one tumor, the lowercase letter "m" (multiple) is added to the "T" stage category. Specific tumor stage information is listed below.

TX: The primary tumor cannot be evaluated.

T0: There is no evidence of a primary tumor in the bladder.

Ta: This refers to noninvasive papillary carcinoma. This kind of growth often is found on a small section of tissue that easily can be removed with TURBT and tends to be recurrent.

Tis: This stage is carcinoma (cancer) in situ, or "flat tumor." This means that the cancer is only found in cells within the lining of the bladder. The doctor may also call it non-muscle-invasive/superficial bladder cancer or noninvasive flat carcinoma (the cancer is on or near the surface of the bladder). This type of bladder cancer often comes back after treatment, usually as another noninvasive cancer in the bladder.

T1: The tumor has spread to the subepithelial connective tissue (the tissue below the inside lining of the bladder).

T2: The tumor has spread to the muscle of the bladder wall.

T2a: The tumor has spread to the inner half of the muscle of the bladder wall (which may be called the superficial muscle.)

T2b: The tumor has spread to the deep muscle of the bladder (the outer half of the muscle).

T3: The tumor has grown into the perivesical tissue (the fatty tissue that surrounds the bladder).

T3a: The tumor has grown into the perivesical tissue, as seen through a microscope.

T3b: The tumor has grown into the perivesical tissue macroscopically, meaning that the tumor(s) is large enough to be seen during imaging tests or to be seen or felt by the doctor.

T4: The tumor has spread to any of the following: the abdominal wall, the pelvic wall, a man’s prostate or seminal vesicle (the tube(s) that carry semen), or a woman’s uterus or vagina.

T4a: The tumor has spread to the prostate, uterus, or vagina.

T4b: The tumor has spread to the pelvic wall or the abdominal wall.

Node. The “N” in the TNM staging system stands for lymph nodes, the tiny, bean-shaped organs that help fight infection. Lymph nodes near where the cancer started, within the true pelvis (called hypogastric, obturator, iliac, perivesical, pelvic, sacral, and presacral lymph nodes), are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: The regional lymph nodes cannot be evaluated.

N0: The cancer has not spread to the regional lymph nodes.

N1: The cancer has spread to a single regional lymph node in the pelvis.

N2: The cancer has spread to more than one regional lymph node in the pelvis.

N3: The cancer has spread to the common iliac lymph nodes, which are located behind the major arteries in the pelvis, above the bladder.

Distant metastasis. The "M" in the TNM system indicates whether the cancer has spread to other parts of the body.

M0: The disease has not metastasized.

M1: There is distant metastasis.

Cancer stage grouping

Doctors assign the stage of the bladder cancer by combining the T, N, and M classifications.

Stage 0a: This is an early cancer that is only found on the surface of the inner lining of the bladder. Cancer cells are grouped together and can often be easily removed. The cancer has not invaded the muscle or connective tissue of the bladder wall. This type of bladder cancer is also called noninvasive papillary urothelial carcinoma (Ta, N0, M0).

Stage 0is: This stage of cancer, also known as flat or carcinoma in situ, is found only on the inner lining of the bladder. It has not grown in toward the hollow part of the bladder, and it has not spread to the thick layer of muscle or connective tissue of the bladder (Tis, N0, M0). This is always a high-grade cancer (see Grading, below).

Stage I: The cancer has grown through the inner lining of the bladder to the lamina propria. It has not spread to the thick layer of muscle in the bladder wall or to lymph nodes or other organs (T1, N0, M0).

Stage II: The cancer has spread into the thick muscle wall of the bladder (also called invasive cancer or muscle-invasive cancer). It has not reached the fatty tissue surrounding the bladder and has not spread to the lymph nodes or other organs (T2, N0, M0).

Stage III: The cancer has spread throughout the muscle wall to the fatty layer of tissue surrounding the bladder. It may also have spread to the prostate in a man or the uterus and vagina in a woman. It has not spread to the lymph nodes or other organs (T3 or T4a, N0, M0).

Stage IV: Any of these conditions:

The tumor has spread to the pelvic wall or the abdominal wall but not to the lymph nodes or other parts of the body (T4b, N0, M0).

The tumor has spread to one or more regional lymph nodes but not to other parts of the body (any T, N1-3, M0).

The tumor may or may not have spread to the lymph nodes but has spread to other parts of the body (any T, any N, M1).

Recurrent cancer: Recurrent cancer is cancer that comes back after treatment. If there is a recurrence, the cancer may need to be staged again (called re-staging) using the system above.

Grading 

Tumor grade. In addition to the TNM system, the cancer may also be evaluated and assigned a grade (G).Doctors use the term “grade” to describe how much the tumor tissue looks like normal bladder tissue under a microscope. Many urologic surgeons classify grading based on the chance that the cancer will recur (come back after treatment) or progress (grow and spread), and plan their treatment based on the grade, using the following categories:

Papilloma. This is also called benign papillary urothelial neoplasm of low malignant potential (PUNLMP). These types of cancer may recur but have a low risk of progressing.

Low grade. These types of cancer are more likely to recur and progress compared with PUNLMP.

High grade. These types of cancer are the most likely to recur and progress.

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