The urinary bladder is a hollow muscular organ and is a part of the urinary system. Urine is made in the kidneys and travels down two tubes called ureters to the bladder. The bladder stores urine, allowing urination to be controlled. The bladder is lined by layers of muscle tissue that stretch to hold urine. During urination, the bladder muscles squeeze, and two sphincters (valves) open to allow urine to flow out.

Fig. 1a: Female urinary system                      Fig. 1b: Male urinary system

The wall of the bladder has 4 main layers.

  1. The innermost lining is called the urothelium or transitional epithelium.
  2. Beneath the urothelium is a thin layer of connective tissue, blood vessels, and nerves.
  3. Next is a thick layer of muscle.
  4. Outside of this muscle, a layer of fatty connective tissue separates the bladder from other nearby organs.

Fig. 2: Layers of the bladder wall

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.

Types of bladder cancer include:

  1. 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.
  2. 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. . 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.

Some bladder cancers include more than one type of cell.

Causes

Causes of bladder cancer include:

  1. Smoking and other tobacco use
  2. Exposure to chemicals, especially working in a job that requires exposure to chemicals
  • Past radiation exposure
  1. Chronic irritation of the lining of the bladder
  2. Parasitic infections

Bladder cancer occurs in men more frequently than it does in women and usually affects older adults, though it can happen at any age.

Signs and symptoms

Bladder cancer signs and symptoms may include:

  • Blood in urine (hematuria)
  • Painful urination
  • Pelvic pain

If you have hematuria, your urine may appear bright red. 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.

Risk factors

Factors that may increase bladder cancer risk include:

  • 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 is 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 certain anti-cancer drugs 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.

Prevention

Although there’s no guaranteed way to prevent bladder cancer, you can take steps to help reduce your risk. For instance:

  • Don’t smoke.Not smoking means that cancer-causing chemicals in smoke cannot collect in your bladder. If you don’t smoke, don’t start. If you smoke, talk to your doctor about a plan to help you stop. Support groups, medications and other methods may help you quit.
  • Take caution around chemicals.If you work with chemicals, follow all safety instructions to avoid exposure.
  • Choose a variety of fruits and vegetables.Choose a diet rich in a variety of colorful fruits and vegetables. The antioxidants in fruits and vegetables may help reduce your risk of cancer.

Diagnosis

  1. Urinalysis:One way to test for bladder cancer is to check for blood in the urine (hematuria). This can be done during a urinalysis, which is a simple test to check for blood and other substances in a sample of urine. This test is sometimes done as part of a general health check-up. Blood in the urine is usually caused by benign (non-cancer) problems, like infections, but it also can be the first sign of bladder cancer. Large amounts of blood in urine can be seen if the urine turns pink or red, but a urinalysis can find even small amounts.
  2. Cystoscopy: A urologist uses a cystoscope, which is a long, thin, flexible tube with a light and a lens or a small video camera on the end. The cystoscope has a lens that allows your doctor to see the inside of your urethra and bladder, to examine these structures for signs of disease. Fluorescence cystoscopy (also known asblue light cystoscopy) may be done along with routine cystoscopy. For this exam, a light-activated drug is put into the bladder during cystoscopy. It’s taken up by cancer cells. When the doctor then shines a blue light through the cystoscope, any cells containing the drug will glow (fluoresce). This can help the doctor see abnormal areas that might have been missed by the white light normally used.

Fig. 3a: Female cystoscopy

Fig. 3b: Male cystoscopy

3.     Transurethral resection of bladder tumor (TURBT)

If an abnormal area (or areas) is seen during a cystoscopy, it needs to be biopsied to see if it’s cancer. A biopsy is when tiny pieces (called samples) of the abnormal-looking tissue are taken out and tested for cancer cells. If bladder cancer is suspected, a biopsy is needed to be sure of the diagnosis. The procedure used to biopsy an abnormal area is a transurethral resection of bladder tumor (TURBT), also known as just a transurethral resection (TUR). During this procedure, the doctor removes the tumor and some of the bladder muscle around the tumor. The removed samples are then sent to a lab to look for cancer. If cancer is found, testing can also show if it has invaded (spread into) the muscle layer of the bladder wall.

4.     Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to make pictures of the inside of your body. If you have bladder cancer, your doctor may order some of these tests to see if the cancer has spread to tissues and organs near the bladder, to nearby lymph nodes, or to distant parts of your body. If an imaging test shows enlarged lymph nodes or other possible signs of cancer spread, some type of biopsy might be needed to confirm the findings.

       i.          Intravenous pyelogram (IVP)

An intravenous pyelogram (IVP), also called an intravenous urogram (IVU), is an x-ray of all of the urinary system taken after injecting a special dye into a vein. This dye is removed from the bloodstream by the kidneys and then passes into the ureters and bladder. X-rays are done while this is happening. The dye outlines these organs on the x-rays and helps show urinary tract tumors. It is important to tell your doctor if you have any allergies or have ever had a reaction to x-ray dyes, or if you have any type of kidney problems. If so, your doctor might choose to do another test instead.

     ii.          Retrograde pyelogram

For this test, a catheter (thin tube) is put in through the urethra and up into the bladder or into a ureter. Then a dye is injected through the catheter to make the lining of the bladder, ureters, and kidneys easier to see on x-rays. This test is not used as often as IVP, but it may be done (along with ultrasound of the kidneys) to look for tumors in the urinary tract in people who cannot have an IVP.

    iii.          Ultrasound

Ultrasound uses sound waves to create pictures of internal organs. It can be useful in determining the size of a bladder cancer and whether it has spread beyond the bladder to nearby organs or tissues. It can also be used to look at the kidneys. This is usually an easy test to have, and it uses no radiation.

  1. Ultrasound-guided needle biopsy:Ultrasound can also be used to guide a biopsy needle into a suspected area of cancer in the abdomen or pelvis.

     v.          Computed tomography (CT) scan

A CT scan uses x-rays to make detailed cross-sectional pictures of your body. A CT scan of the kidney, ureters, and bladder is called a CT urogram. It can provide detailed information about the size, shape, and position of any tumors in the urinary tract, including the bladder. It can also help show enlarged lymph nodes that might contain cancer, as well as other organs in the abdomen (belly) and pelvis.

  1. CT-guided needle biopsy:CT scans can also be used to guide a biopsy needle into a suspected tumor. This is not done to biopsy tumors in the bladder, but it can be used to take samples from areas where the cancer may have spread. To do this, you lie on the CT scanning table while the doctor advances a biopsy needle through your skin and into the tumor.

  vii.          Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI images are very useful in showing cancer that has spread outside of the bladder into nearby tissues or lymph nodes. A special MRI of the kidneys, ureters, and bladder, known as an MRI urogram, can be used instead of an IVP to look at the upper part of the urinary system.

viii.          Chest x-ray

A chest x-ray may be done to see if the bladder cancer has spread to the lungs. This test is not needed if a CT scan of the chest has been done.

    ix.          Bone scan

A bone scan can help look for cancer that has spread to bones. This test is usually not done unless you have symptoms such as bone pain, or if blood tests show the cancer might have spread to your bones. For this test, you get an injection of a small amount of low-level radioactive material, which settles in areas of damaged bone throughout your body. A special camera detects the radioactivity and creates a picture of your skeleton. A bone scan may suggest cancer in the bone, but to be sure, other imaging tests such as plain x-rays, MRI scans, or even a bone biopsy might be needed.

Your doctor uses information from these procedures to assign your cancer a stage. The stages of bladder cancer are indicated by Roman numerals ranging from 0 to IV. The lowest stages indicate a cancer that is confined to the inner layers of the bladder and that hasn’t grown to affect the muscular bladder wall. The highest stage — stage IV — indicates cancer has spread to lymph nodes or organs in distant areas of the body.

Treatment

Treatment options for bladder cancer depend on a number of factors, including the type of cancer, grade of the cancer and stage of the cancer, which are taken into consideration along with your overall health and your treatment preferences.

Bladder cancer treatment may include:

  1. Surgery,to remove cancerous tissue
  2. Reconstruction,to create a new way for urine to exit the body after bladder removal
  3. Chemotherapy in the bladder (intravesical chemotherapy) to increase the chance for a cure in a person having surgery to remove the bladder, or as a primary treatment in cases where surgery isn’t an option or for the whole body (systemic chemotherapy),to increase the chance for a cure in a person having surgery to remove the bladder, or as a primary treatment in cases where surgery isn’t an option
  4. Radiation therapy,to destroy cancer cells, often as a primary treatment in cases where surgery isn’t an option or isn’t desired
  5. Immunotherapy,to trigger the body’s immune system to fight cancer cells, either in the bladder or throughout the body
  6. Multimodality therapy, a combination of treatment approaches may be recommended by your doctor and members of your care team.
  7. Bladder cancer surgery

Approaches to bladder cancer surgery might include:

  1. Transurethral resection of bladder tumor (TURBT).TURBT is a procedure to remove bladder cancers confined to the inner layers of the bladder, those which aren’t yet muscle-invasive cancers. During the procedure, a surgeon passes a small wire loop through a cystoscope and into the bladder. The wire loop burns away cancer cells using an electric current. Alternatively, a high-energy laser may be used to destroy the cancer cells.

TURBT is performed under regional anesthesia — where medication given numbs only the lower part of your body — or general anesthesia — where medication puts you to sleep during the surgery. Because doctors perform the procedure through the urethra, you won’t have any cuts (incisions) in your abdomen.

As part of the TURBT procedure, your doctor may recommend a one-time injection of cancer-killing medication (chemotherapy) into your bladder to destroy any remaining cancer cells and to prevent a tumor from coming back. The medication remains in your bladder for up to an hour and then is drained.

  1. Cystectomy is surgery to remove all or part of the bladder. During a partial cystectomy, your surgeon removes only the portion of the bladder that contains a single cancerous tumor. Partial cystectomy may only be an option if cancer is limited to one area of the bladder that can easily be removed without harming bladder function.

A radical cystectomy is an operation to remove the entire bladder, part of the ureters and surrounding lymph nodes. In men, radical cystectomy typically includes removal of the prostate and seminal vesicles. In women, radical cystectomy also involves removal of the uterus, ovaries and part of the vagina.

Cystectomy carries a risk of infection and bleeding. In men, removal of the prostate and seminal vesicles may cause erectile dysfunction. But, your surgeon may be able to spare the nerves necessary for an erection. In women, removal of the ovaries causes infertility and premature menopause.

  1. Reconstruction, to create a new way for urine to exit the body after bladder removal
  1. Neobladder reconstruction.After a radical cystectomy, your surgeon must create a new way for urine to leave your body (urinary diversion). One option for urinary diversion is neobladder reconstruction. Your surgeon creates a sphere-shaped reservoir out of a piece of your intestine. This reservoir, often called a neobladder, sits inside your body and is attached to your urethra. In most cases, the neobladder allows you to urinate normally. A small number of people with a neobladder have difficulty emptying the neobladder and may need to use a catheter periodically to drain all the urine from the neobladder (See Fig. 4).

Fig. 4: Neobladder reconstruction

  1. Ileal conduit.For this type of urinary diversion, your surgeon creates a tube (ileal conduit) using a piece of your intestine. The tube runs from your ureters, which drain your kidneys, to the outside of your body, where urine empties into a pouch (urostomy bag) you wear on your abdomen (see Fig. 5).

Fig 5: Ileal conduit

  • Continent urinary reservoir.During this type of urinary diversion procedure, your surgeon uses a section of intestine to create a small pouch (reservoir) to hold urine, located inside your body. You drain urine from the reservoir through an opening in your abdomen using a catheter a few times each day.
  1. Chemotherapy

Chemotherapy uses drugs to kill cancer cells. Chemotherapy treatment for bladder cancer usually involves two or more chemotherapy drugs used in combination.

Chemotherapy drugs can be given:

  1. Through a vein in your arm (intravenously)
  2. Via a tube passed through your urethra directly to your bladder (intravesical therapy)

Chemotherapy is frequently used before bladder removal surgery to increase the chances of curing the cancer. Chemotherapy may also be used to kill cancer cells that might remain after surgery. Chemotherapy is sometimes combined with radiation therapy in very select cases as an alternative to surgery.

Intravesical chemotherapy may be the primary treatment for superficial bladder cancer, where the cancer cells affect only the lining of the bladder and not the deeper muscle tissue. Or sometimes immunotherapy may be administered as intravesical therapy for superficial bladder cancer.

  1. Radiation therapy

Radiation therapy uses high-energy beams aimed at your cancer to destroy the cancer cells. Radiation therapy for bladder cancer usually is delivered from a machine that moves around your body, directing the energy beams to precise points. In select cases, radiation therapy is sometimes combined with chemotherapy as an alternative to surgery or when surgery is not an option.

  1. Immunotherapy

Immunotherapy, also called biological therapy, works by signaling your body’s immune system to help fight cancer cells. Immunotherapy for bladder cancer often is administered through the urethra and directly into the bladder (intravesical therapy).

  1. Multimodality therapy

Using a three-prong treatment approach may preserve the bladder in certain cases of muscle-invasive disease. Known as trimodality therapy, the treatment approach includes TURBT, chemotherapy and radiation therapy. First, your surgeon performs a TURBT procedure to remove as much cancerous tissue as possible from your bladder, while maintaining bladder function. After TURBT, you undergo a regimen of chemotherapy along with radiation therapy, which both take place during the first several weeks after surgery. If, after trying trimodality therapy, not all of the cancer is gone or you have a recurrence of muscle-invasive cancer, your surgeon may recommend a radical cystectomy.