Bladder Cancer

What Is Bladder Cancer? What Causes Bladder Cancer?

Bladder cancer, or cancer of the bladder, is cancer that forms in the tissues of the bladder. The bladder is an organ that stores urine. The majority of bladder cancers are transitional cell carcinomas - the cancer starts in cells of the inner-lining of the bladder.

Cancer that starts in thin, flat cells of the bladder are also possible; this type is called squamous cell carcinoma. Adenocarcinoma is also possible - this type of cancer begins in the cells that make and release mucus and other fluids.

According to the National Cancer Institute, 70,980 new diagnoses and 14,330 deaths from bladder cancer are estimated to occur in 2009 in the USA. It is the seventh most common cancer in the United Kingdom, where approximately 10,000 diagnoses are made each year. In the UK 3,300 men and 1,600 women are estimated to die of bladder cancer each year.

Smoking is believed to be responsible for about half of all bladder cancer cases in the USA. The National Health Service (NHS), United Kingdom, estimates that smoking causes 50%-60% of male bladder cancers and 20%-30% of female bladder cancers.

Bladder cancer tends to affect older adults, but can develop in any age group. The disease is highly treatable at an early stage, when fortunately most diagnoses are made. Nevertheless, bladder cancer has a high rate of recurrence (coming back), even if treated early on. That is why survivors should undergo regular follow-up screening tests.

The outlook for non-invasive bladder cancer is good with 90% of patients surviving for at least five years after diagnosis, and many surviving substantially longer.

What are the risk factors for bladder cancer?

In medicine, a risk factor is something that raises the chances of developing a disease or condition. For example, people who smoke are more likely to develop heart disease. Therefore, smoking is a risk factor for heart disease. The risk factors linked to bladder cancer are:
  • Age - bladder cancer is extremely rare for people aged under 40 years, and is much more common among patients aged 65 or over.
  • Bladder defect - people who were born with a bladder defect are more susceptible to developing adenocarcinoma of the bladder.
  • Cancer therapies - women who received radiation therapy (radiotherapy) for cervical cancer have been found to have a higher risk of subsequently developing bladder cancer. Cyclophosphamide (Cytoxan) and ifosfamide (Ifex), chemotherapy drugs used for treating cancer, may also pose an elevated risk. However, it appears that men who receive radiotherapy for prostate cancer do not have a higher risk of developing bladder cancer later on.
  • Chronic inflammation of the bladder - in medicine, chronic means long-term or repeated. People with chronic bladder inflammations (cystitis) have a higher risk of developing squamous cell bladder cancer. Chronic inflammation of the bladder may be caused by long-term use of a urinary catheter. There is a parasitic infection which may cause chronic inflammation of the bladder, which is linked to squamous cell carcinoma risk.
  • Ethnic background - Caucasian (white) people are more likely to develop bladder cancer compared to people of other racial backgrounds.
  • Exposure to certain chemicals - people exposed to arsenic, as well as chemicals used in the manufacture of rubber, dyes, textiles, plastics, paints and leather run a higher risk of developing bladder cancer, compared to others. Smokers who are also exposed to one or more of these chemicals are especially at risk. When such chemicals enter our bodies our kidneys filter them from the bloodstream and move them into the bladder, where they will eventually be expelled in urine. 
  • The following chemicals are known to increase the risk of developing bladder cancer:

      Aniline dyes 2-Naphthylamine 4-Aminobiphenyl Xenylamine Benzidine

    During the 1970s and 1980s a link between bladder cancer and occupations and chemical exposure was found. Since then new laws have come in which have significantly reduced human exposure. It is expected that occupation-related cases of bladder cancer should fall in the future. The number of occupation-related cases of bladder cancer continues to be fairly high because it can take a long time after initial exposure for the risk to go away.
  • Family history - an individual who has a close relative, a parent or sibling, who has/had bladder cancer, has a higher risk than others. However, the risk of developing bladder cancer if you have a close relative who has/had it is still low. People who have a close family member who has/had hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, has a higher risk of developing bladder cancer, as well as some other cancers.
  • Gender - bladder cancer is almost twice as common among males as females.
  • Having had bladder cancer before - anybody who has had bladder cancer before is at a significantly higher risk of getting it again one day, compared to somebody who has never had it. The cancer can recur in the ureters or urethra; not only in the bladder.
  • Smoking - harmful chemicals can build up in the urine of smokers, which in turn increase the risk of bladder cancer. A smoker processes the chemicals in the smoke and excretes them in the urine. The lining of the bladder, which stores the urine, can become damaged because of these chemicals - making them more susceptible to cancer.

What causes bladder cancer?

The bladder is a hollow, balloon-shaped organ that stores urine. It is in the abdomen (pelvis). Waste from blood is filtered in the kidneys - the waste liquid is called urine. Urine travels from the kidney through two tubes, called ureters, to the bladder. When a person urinates, the urine travels through another tube, called the urethra to an opening at the end of a male's penis or just in front of a female's vagina. In males the urethra is longer because is passes through the prostate gland and then through the whole length of the penis.

How does cancer develop?

Most healthy cells live for a set time, die, and new ones are made to replace the dead ones. Cancer occurs when something goes wrong with cell reproduction and death - the cells do not die, but continue reproducing.

If cells are not dying and new ones are taking their place, eventually there will be too many of them, and you start getting a lump (a tumor). As more and more excess cells appear they occupy more and more space, displacing healthy cells, until eventually there is not sufficient room for enough healthy cells - the patient becomes ill, and may eventually die.

Different types of bladder cells can go wrong (mutate) and become cancerous. The type of treatment a bladder cancer patient receives will depend on the type they have. The following are examples of types of bladder cancers:
  • Transitional cell carcinoma - the cells the line the inside of the bladder become cancerous. When the bladder is full, transitional cells expand; when it is empty they contract. As these cells also exist in the inside lining of the ureters and urethra, tumors can form there as well. In the USA and Europe this is the most common type of bladder cancer.
  • Squamous cell carcinoma - a squamous cell appears in the bladder when there is irritation or infection. They can eventually become cancerous. Squamous cell bladder cancer is more common in countries where schistosomiasis occurs. Schistosomiasis is a parasitic infection.
  • Adenocarcinoma - these are mucus-secreting glands in the bladder. When their cells become cancerous it is called adenocarcinoma.
Sometimes, bladder cancer may consist of more than one type of cancerous cell.

What are the symptoms of bladder cancer?

A symptom is something the patient feels or reports, while a sign is something other people, including a doctor, may detect. For example, pain may be a symptom while a rash could be a sign.

The most common signs and symptoms are:
  • Hematuria - blood in urine (by far the most common symptom). It may appear Coca-Cola colored, or bright red in the urine. It could also appear in a microscopic examination of the urine.
  • More frequent urinations than usual
  • Urinary tract infection
  • Sudden urges to urinate
  • Pain when urinating; usually a burning sensation
The patient may also experience the following symptoms, but they are less common:
  • Pain in the pelvis
  • Back pain
  • Bone pain
  • Unexplained weight loss
  • Swelling of the legs
Any blood in urine should be reported to your doctor immediately. However, it most likely is not bladder cancer. Less than 1 in 1,000 cases of hematuria (blood in urine) are caused by bladder cancer. Nevertheless, this does not mean you should ignore it. Blood in urine may be a sign of several other medical conditions, as well as bladder cancer.

How is bladder cancer diagnosed?

  • Urine sample - if the patient had detected blood in urine the GP (general practitioner, primary care physician) will ask for a urine sample, which will be tested for abnormal cells; this called a urinary cystography. Although this test is useful it can sometimes give false-positive results, and vice-versa - detect abnormal cells when there is not cancer, or not detect abnormal cells when cancer is present. A doctor cannot make a diagnosis just from a urine test.

    The urine sample will also be tested for bacteria.
  • Physical examination - the doctor will carry out a physical examination. This may include an examination of the rectum and vagina for women, and just the rectum for men.
If the doctor requires more data, or if bladder cancer is suspected, the GP will probably refer the patient to a urologist. A urologist, or urological surgeon, is a doctor who specializes in just diseases of the urinary organs in females, and the urinary organs and sex organs in males. The urologist may recommend the following tests:
  • Imaging tests - these tests allow the doctor to observe the structures of the urinary tract. The patient may receive a dye which is either injected into a vein or swallowed. An intravenous pyelogram is an X-ray imaging test that sees the dye highlighted in the bladder, ureters and kidneys. A CT (computerized tomography) scan is a series of X-ray images that allows the doctor to have a better look at the urinary tract and surrounding tissues.
  • Cystoscopy - a long-thin flexible tube, a cystoscope, is inserted through the patient's urethra and into the bladder. The device has a lens telescope or microscope, and a fiber-optic lighting system which allows the health care provider to observe the inside of the bladder and urethra. The patient will receive a local anesthetic before this procedure begins. The urologist looks out for any abnormal areas that could be caused by bladder cancer.

    Many cystoscopes have extra tubes which can guide other devices for procedures to treat urinary problems.
  • Biopsy - a more rigid type of cystoscope may be used to take a sample of bladder tissue. The tissue will be observed under a microscope to see whether it is cancerous. This procedure is sometimes called TURBT (transurethral resection of bladder tumor). TURBT is sometimes used to treat bladder cancer. The patient is usually given a general anesthetic.
If results come back positive - if cancerous cells are detected in the bladder lining, the patient may have to undergo further tests to determine whether the cancer is limited to its area of origin, or has spread. These tests might include:
  • Chest X-rays
  • CT (computer tomography) scan - this is a medical imaging method that employs tomography. Tomography is the process of generating a two-dimensional image of a slice or section through a 3-dimensional object (a tomogram).
  • MRI (magnetic resonance imaging) scan - this device uses a magnetic field and radio waves to create detailed images of the body.
  • A bone scan - some radioactive material is injected into the patient's vein. Affected areas of bone will absorb this material more rapidly than unaffected bone - these will show up as hot-spots in the scan.

Stages of bladder cancer

  • Stage I - the cancer exists just in the inner lining of the bladder. It has not yet invaded the bladder wall.
  • Stage II - the cancer has invaded the bladder wall.
  • Stage III - the cancer has gone through the bladder wall and has spread to surrounding tissue. In men this could include the prostate, and in women the vagina or uterus. 
  • Stage IV - the cancer has spread to the lymph nodes and other organs, such as the liver, bones or lungs.

What are the treatment options for bladder cancer?

Treatment for bladder cancer depends on the type of cancer, how advanced it is, the patient's general health, and his/her preferences.

Surgery
  • Early-stage bladder cancer

    • TURBT (transurethral resection of bladder tumor) - this procedure is used when the cancer is confined to the inner layers of the bladder. The surgeon passes a wire loop through the patient's urethra and into the bladder. The loop burns away cancer cells by means of fulguration (electric current). The patient may feel some pain and have blood in his/her urine for a few days.
    • Segmenta cystectomy (partial cystectomy) - a portion of the bladder that contains cancer cells is surgically removed. This procedure is an option of the cancer is limited to just one part of the bladder that can be surgically removed without seriously affecting bladder function. The patient will receive a general anesthetic and remain in hospital for between seven to ten days. There is a risk of bleeding and infection. There may also be bleeding. As the procedure reduces the size of the bladder the patient will need to urinate more often after it. Some patients find that eventually the intervals between each urination get longer.
  • Invasive bladder cancer (later stage)

    • Radical cystectomy - the whole bladder is surgically removed, as well as nearby lymph nodes. For males this also includes the removal of the prostate and seminal vesicles, which will cause infertility. For females this also includes removal of the uterus, ovaries (causing infertility) and part of their vagina. The younger woman will experience premature menopause. There is a risk of infection, blood clots, bleeding and bowel obstruction.

      With the entire bladder removed the surgeon needs to create a new route for the urine to leave the body. A urinary conduit (a tube) using a piece of the patient's intestine can be created, which goes from the kidneys to the outside of the body where the urine drains into an urostomy bag. The bag is worn on the patient's abdomen.

      Alternatively the surgeon may use a section of intestine to create a small internal reservoir for urine; this is called a cutaneous continent urinary diversion. The reservoir can be drained by inserting a catheter into a hole in the abdomen.

      The surgeon can also create a neobladder from a piece of intestine. This internal reservoir is connected to the urethra, so that the patient can urinate in a normal way. Sometimes a catheter may be needed.
Immunotherapy

Also known as biological therapy, immunotherapy signals the immune system to help attack cancer cells. Intravesical therapy is administered through the patient's urethra straight into the bladder. The following drugs may be used:
  • BCG (Bacille Calmette-Geurin) - the BCG vaccine is administered to non-invasive bladder cancer patients in order to reduce the risk of recurrence. The vaccine was originally designed to treat TB (tuberculosis). Experts are not sure how it helps patients with non-invasive bladder cancer. We do know that it triggers the immune system to target any remaining cancer cells. The bladder can become irritated and the patient may have blood in his/her urine. Some patients may experience flu-like symptoms.
  • Interferon alfa - this is a synthetic version of interferon; a type of cell the body uses to fight infections. It may be used in combination with BCG. Interferon alfa may also cause flu-like symptoms.

    The patient may receive biological therapy after TURBT to reduce the risk of cancer recurrence. It may also be administered before surgery to make a tumor smaller and easier for the surgeon to deal with.
Chemotherapy

These drugs either destroy cancer cells or prevent them from multiplying. Bladder cancer patients will usually receive two drugs at the same time. They are administered intravenously or directly into the bladder via the urethra.

The doctor may administer chemotherapy after surgery to destroy any cancer cells that might remain inside the body. Sometimes chemotherapy is administered before surgery to shrink the tumor and make it more manageable.

Sometimes chemotherapy is given along with radiotherapy.

Radiotherapy

Radiotherapy, also known as radiation therapy, radiation oncology and XRT, is used for treating cancer, thyroid disorders and some blood disorders. Approximately 40% of patients of all types of cancer undergo some kind of radiotherapy. It involves the use of beams of high-energy X-rays or particles (radiation) to destroy cancer cells. Radiotherapy works by damaging the DNA inside the tumor cells, destroying their ability to reproduce.

The patient may receive external beam radiation - therapy comes from a machine outside the body, or brachytherapy - a device is placed inside the bladder.

Radiotherapy may be used prior to surgery to make the tumor smaller, so that it is easier to remove. It may also be used after surgery to kill off any cancers cells that may have been left behind. Sometimes radiation therapy is given along with chemotherapy.

What are the possible complications of bladder cancer?

Recurrence

As bladder cancer often comes back (recurs) patients have to undergo follow-up tests for some years after they have been cured. The frequency and kinds of tests depend on the type of cancer the patient had, as well as the treatment he/she received. Follow-up tests may include:
  • Cystoscopy - the doctor uses a cystoscope which goes up the urethra and into the bladder so that he/she can have a look inside.
  • Urine cytology test - this urine test can detect cancer cells.
  • Taking samples of bladder tissue - patients considered to be at high risk of recurrence may have samples of bladder tissue checked at certain times. This allows the doctor to detect bladder cancer before it is visible with a cystoscope.
Most doctors advise follow-up testing every three months for two years after bladder cancer treatment. Patients with more aggressive cancers may undergo more frequent testing.

Preventing bladder cancer recurrence

  • Give up smoking
  • Diet - make sure you eat plenty of fruit and vegetables so that your vitamin intake is high. There is some limited evidence that a diet high in fruit and vegetables, and low in certain fats can lower a patient's risk of bladder cancer coming back. Even though this evidence is limited, following a healthy diet will definitely help prevent other diseases, such as some other cancers, hypertension, and heart disease.
  • Be careful with chemicals - if you work with chemicals make sure you follow all the safety instructions carefully.
  • Test your well for arsenic - if you have a well, have it tested for levels of arsenic in the water.
  • Drink plenty of water - if you drink plenty of water any levels of toxins in your bladder (and the rest of your body) will be diluted and flushed out more regularly.
  • Join a clinical trial - sometimes there are clinical trials that look at new ways of preventing bladder cancer recurrence. Although a trial does not guarantee anything (that is why it is called a trial), the patient does have the opportunity to take part in research that will help lower the risk of cancer recurrence for patients in the future.
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