What is bladder cancer?
The bladder, a hollow organ in the lower part of the abdomen, serves as a reservoir for urine until it is discharged out of the body through the urethra.
There are different types of bladder cancer. The cancer cell type can be transitional cell carcinoma, squamous cell carcinoma or adenocarcinoma—each named for the types of cells that line the wall of the bladder where the cancer originates.
- Most bladder cancers (more than 90 percent) start from the transitional cells, which occupy the innermost lining of the bladder wall. The cancers, which originate in these cells lining the bladder can, in some instances, invade into the deeper layers of the bladder (called the lamina propria), the thick muscle layer of the bladder, or through the bladder wall into the fatty tissues that surround the bladder.
- Squamous cells are thin flat cells that line the urethra and can form in the bladder after long bouts of bladder inflammation or irritation. Squamous cell carcinoma makes up about 5 percent of bladder cancers.
- Adenocarcinoma is a very rare type of bladder cancer that begins in glandular (secretory) cells in the lining of the bladder. Only 1 percent to 2 percent of bladder cancers are adenocarcinoma.
What are the stages of bladder cancer?
Bladder cancer can be either early stage (confined to the lining of the bladder) or invasive (penetrating the bladder wall and possibly spreading to nearby organs or lymph nodes).
The stages range from TA (confined to the internal lining of the bladder) to IV (most invasive). In the earliest stages (TA, T1 or CIS), the cancer is confined to the lining of the bladder or in the connective tissue just below the lining, but has not invaded into the main muscle wall of the bladder.
Stages II to IV denote invasive cancer:
- In Stage II, cancer has spread to the muscle wall of the bladder.
- In Stage III, the cancer has spread to the fatty tissue outside the bladder muscle.
- In Stage IV, the cancer has metastasized from the bladder to the lymph nodes or to other organs or bones.
A more sophisticated and preferred staging system is known as TNM, which stands for tumor, node involvement and metastases. In this system:
- Invasive bladder tumors can range from T2 (spread to the main muscle wall below the lining) all the way to T4 (tumor spreads beyond the bladder to nearby organs or the pelvic side wall).
- Lymph node involvement ranges from N0 (no cancer in lymph nodes) to N3 (cancer in many lymph nodes, or in one or more bulky lymph nodes larger than 5 cm).
- M0 means that there is no metastasis outside of the pelvis. M1 means that it has metastasized outside of the pelvis.
Symptoms and Causes
What are the warning signs of bladder cancer?
Some symptoms of bladder cancer are also symptoms of other conditions, and should prompt a visit to your physician. Blood in the urine is the most important warning sign. Pain during urination, frequent urination or difficulty urinating are other symptoms.
Diagnosis and Tests
What tests will I have if my doctor suspects bladder cancer or another urinary problem?
Your doctor will want to analyze your urine (urinalysis) to determine if an infection could be a cause of your symptoms. A microscopic examination of the urine, called cytology, will look for cancer cells.
A cystoscopy is the main procedure to identify and diagnose bladder cancer. In this procedure, a lighted telescope (cystoscope) is inserted into your bladder from the urethra to view the inside of the bladder and, when done under anesthesia, take tissue samples (biopsy), which are later examined under a microscope for signs of cancer. When this procedure is done in the doctor’s office, local anesthesia gel is placed into the urethra prior to the procedure to minimize the discomfort.
If the diagnosis of bladder cancer is made, then the next step is to remove the tumor for detailed staging and diagnosis.
Transurethral resection (TURBT) is a procedure done under general or spinal anesthesia in the operating room. A telescope is inserted into the bladder and the tumor is removed by scraping it from the bladder wall (a portion of the bladder wall is removed with it), using a special cystoscope (called a resectoscope). This procedure is diagnostic as well as therapeutic.
This often can be done as an outpatient procedure, with patients discharged from hospital the same day. After removal, the tumor is analyzed by a pathologist, who will determine the type of tumor, the tumor grade (aggressiveness) and the depth of invasion. The purpose of the procedure is to remove the tumor and obtain important staging information (such as the tumor grade and depth of invasion).
For some patients with invasive cancer, a CT scan of the abdomen and pelvis might be the next step to determine if there is any spread of the disease outside of the bladder.
Magnetic resonance imaging, which uses a magnet, radio waves, and a computer to take detailed images, can also be done, and is helpful in planning additional treatment.
A chest X-ray may also be performed to detect if any cancer has spread to the lungs. At times, a bone scan may be performed to look for metastasis (spread) of the cancer to the bone. Most of these tests are used selectively, i.e., only in certain patients with related symptoms.
Once bladder cancer is diagnosed, staging of the disease is done using the tests described above. The stage of the disease will determine the treatment course.
Management and Treatment
What are the treatment options for bladder cancer?
There are four types of treatment for patients with bladder cancer. These include:
- Intravesical chemotherapy or immunotherapy for superficial cancers
- Radiation therapy
Sometimes, combinations of these treatments will be used.
Surgery is a common treatment option for bladder cancer. The type of surgery chosen will depend on the stage of the cancer.
- Transurethral resection of the bladder is used most often for early stage disease (TA, T1, or CIS). It is done under general or spinal anesthesia. In this procedure, a special telescope called a resectoscope is inserted through the urethra into the bladder. The tumor is then trimmed away with the resectoscope, using a wire loop, and the raw surface of the bladder is then fulgurated (destroyed with an electric current).
- Partial cystectomy is the removal of a section of the bladder. At times, it is used for a single tumor that invades the bladder wall in only one region of the bladder. This type of surgery retains most of the bladder. Chemotherapy or radiation therapy is often used in combination. Only a minority of patients will qualify for this bladder-sparing procedure.
- Radical cystectomy is complete removal of the bladder. It is used for more extensive cancers and those that have spread beyond the bladder (or several early tumors over a large portion of the bladder).
This surgery is often done using a robot, which removes the bladder and any other surrounding organs. In men, this is the prostate and seminal vesicles. In women, the ovaries, uterus and a portion of the vagina may be removed along with the bladder.
Because the bladder is removed, a procedure called a urinary diversion must be done so that urine can exit the body. A pouch constructed of intestine may be made inside the body, or a leak-proof bag worn outside the body may be used to collect urine. The procedure typically requires a hospital stay of five to six days, give or take a few either way.
Chemotherapy refers to the use of any of a group of drugs whose main effect is either to kill or slow the reproduction of rapidly multiplying cells. Cancer cells absorb chemotherapy drugs faster than normal cells do (but all cells are exposed to the chemotherapy drug). Chemotherapy drugs are delivered intravenously (through a vein) or can be delivered intravesically (directly into the bladder through a catheter threaded through the ureter), depending on the stage of the cancer.
Some common chemotherapy drugs that are used for the treatment of bladder cancer include:
Many of these drugs are used in combinations.
Side effects can occur with chemotherapy, and their severity depends on the particular drug used and the ability of the patient to tolerate the drugs. Common side effects from chemotherapy include:
- Nausea and vomiting
- Loss of appetite
- Hair loss
- Tiredness from anemia
- Vulnerability to infections
- Ulcers or sores in the mouth
Chemotherapy can be used alone, but is often used with surgery or radiation therapy.
Bladder cancer may be treated with intravesical (into the bladder through a tube inserted into the urethra) immunotherapy or chemotherapy.
Immunotherapy refers to using the body's own immune system to attack the cancer cells. A vaccine called Bacillus Calmette-Guérin (BCG) is commonly used for this purpose in the intravesical treatment of stages Ta, T1, or carcinoma in situ (limited to the innermost lining) bladder cancers. In the procedure, a solution containing BCG is retained in the bladder for a few hours before being drained.
Intravesical BCG is usually given once a week for six weeks, but sometimes long-term maintenance therapy is needed. Bladder irritation, pain or burning during urination, and low-grade fever and chills are possible side effects of intravesical BCG.
Intravesical chemotherapy with mitomycin C is another treatment option. Because the chemotherapy is given directly into the bladder, other cells in the body aren't exposed to the chemotherapy, which reduces the chances for side effects from the chemotherapy. It's also often given as a single dose after a tumor has been removed via cystoscopy.
Radiation therapy damages the DNA of cancer cells by bombarding them with high-energy X-rays or other types of radiation. It may be an alternative to surgery or used in combination with surgery or chemotherapy. Radiation therapy can be delivered externally or internally.
In external radiation therapy, the radiation source is a machine outside the body that directs a focused beam of radiation at the tumor. With better imaging technologies in use today, computer-guided radiation delivered from several angles minimizes radiation exposure to surrounding tissues and organs, limiting damage to these tissues. Fatigue, swelling of soft tissues and skin irritation are common side effects of external radiation.
Internal radiation therapy is not often used for bladder cancer. In this type of treatment, a radioactive pellet is inserted into the bladder through the urethra or an incision in the lower abdomen. Internal radiation requires a hospital stay during the course of treatment, which can be several days, after which the pellet is removed.
What are the risk factors for bladder cancer?
Some factors increase the risk of bladder cancer:
- Cigarette smoking is the biggest risk factor; it more than doubles the risk. Pipe and cigar smoking and exposure to second-hand smoking may also increase one's risk.
- Prior radiation exposure is the next most common risk factor (e.g., as treatment for cervical cancer, prostate cancer or rectal cancer).
- Certain chemotherapy drugs (e.g., cyclophosphamide) also increase the risk of bladder cancer.
- Environmental exposures increase the risk of bladder cancer. People who work with chemicals, such as aromatic amines (chemicals used in dyes) are at risk. Extensive exposure to rubber, leather, some textiles, paint, and hairdressing supplies, typically related to occupational exposure, also appears to increase the risk.
- Infection with a parasite known as Schistosoma haematobium, which is more common in developing countries and the Middle East. (This organism is not found in the United States.)
- People who have frequent infections of the bladder, bladder stones, or other diseases of the urinary tract, or who have chronic need for a catheter in the bladder, may be at higher risk of squamous cell carcinoma.
- Patients with a previous bladder cancer are at increased risk to form new or recurrent bladder tumors.
Other risk factors include diets high in fried meats and animal fats, and older age. In addition, men have a three-fold higher risk than women.