Bladder cancer

Summary

• The bladder is located in the lower abdomen and forms part of the urinary tract.
• Most bladder cancers start in the cells lining the bladder.
• The most common type is transitional cell cancer, which accounts for 90-95 % of bladder cancers.
• It does not tend to run in families, but the cells of certain individuals seem to be more susceptible to malignant change than others.
• The most common symptom of bladder cancer is blood in the urine. 

Description

The bladder is located in the lower abdomen and forms part of the urinary tract. It is a hollow organ that stores urine. The two kidneys filter the blood and form urine, which is then passed down the ureters to the bladder for storage. The bladder has a strong muscular wall to allow it to expand and accommodate urine.

The inside of the hollow bladder is lined with specialised cells called transitional cell epithelium. During urination, the bladder muscle contracts and expels urine via the urethra.

Most bladder cancers start in the cells lining the bladder. The most common type is transitional cell cancer, which accounts for 90-95 % of bladder cancers. Squamous carcinoma and adenocarcinoma account for the rest.

If the cancer is limited to the bladder lining only, it is called superficial bladder cancer. If it invades through the lining and into the muscle or beyond, then it is called invasive bladder cancer. Cancer cells may also spread via lymph channels to the lymph nodes, or via the bloodstream to distant organs like the lungs or bone. When this happens, it is called metastatic bladder cancer.

Causes

The exact cause of bladder cancer is not known. Research is being done to try and identify a gene which may increase the risk of developing bladder cancer. Certainly cells of certain individuals seem to be more susceptible to malignant change than other individuals. Several potential carcinogens have been identified, and are believed to be excreted into the urine, where they act on the lining of the bladder, eventually causing tumour formation. The time period between exposure and cancer may be as long as 20 years.

A risk factor is anything which may increase the chances of getting a cancer, but which does not directly cause it.

Smoking

This is by far the biggest risk factor. Cigarette smokers have a two to fourfold increased risk of bladder cancer, compared to non-smokers. The risk persists for about 10 years after cessation of smoking. Pipe and cigar smokers are also at increased risk.

Industrial chemicals

Exposure to certain chemicals, especially aromatic amines, has been linked with bladder cancer. These chemicals are used in the dye, rubber, textile, paint and printing industries.

Chronic bladder inflammation

Recurrent infection, stones, and indwelling catheters have all been linked to bladder cancer - especially squamous carcinoma. Chronic infection with Schistosoma haematobium (bilharzia) may also predispose to bladder cancer.

Drugs

Some drugs have been linked to bladder cancer (eg: Cyclophosphamide, which is used in some cancer treatment).

Dietary factors

Fried meat and diets high in saturated fats have been linked to bladder cancer. Use of the Chinese herb, Aristocholia fangschi, has also been associated with it.

Age

Risk of bladder cancer increases with age. It is very uncommon under the age of 40, and median age at diagnosis is 65 years. Men are affected more than women.

Race

Whites are twice as likely as blacks to get bladder cancer.

Symptoms

The most common symptom of bladder cancer is blood in the urine. The colour may range from slight pink to rusty or bright red. Small amounts of blood may not be seen at all, and may only be picked up when testing the urine. The bleeding may be present sporadically or constantly.

As many other less sinister things can also cause blood in the urine, it is important to seek medical help and find the cause of this symptom.

Other symptoms associated with bladder cancer are:

• Pain during urination
• Frequent urination
• Feeling the need to pass urine but being unable to do so
• Flank pain or pelvic discomfort
• Unexplained weight loss

Course

At time of diagnosis, 75% of bladder tumours are superficial, 20 to 25% are invasive and 5 to 20% present with metastases. Despite treatment, 50 to 70% of patients with superficial bladder cancer will develop recurrence within 5 years, and 5 to 20% of superficial tumours will progress to more advanced disease.

Bladder tumours are graded from one to three according to pathological features, with grade one the least aggressive and grade three the most aggressive. Almost all invasive bladder cancers are grade three.

Diagnosis

To investigate the cause of the symptoms, the doctor will ask your medical history and do a full examination, which may involve a vaginal and/or rectal examination to check for pelvic masses. He/she will also send urine to the laboratory to check for blood and for cancer cells. If anything suspicious is found at this visit, then you will be referred to a specialist urologist who will do a cystoscopy examination. This involves using a special instrument to look directly inside the bladder. It is done through the urethra.

The examination may be done in theatre under local or general anaesthesia. If anything suspicious is seen, a small piece will be removed and sent to the pathology laboratory for examination under the microscope. This is called a biopsy. If the lesion is small, it may be completely removed at biopsy.

The pathologist will then determine the grade of the specimen. That is: how aggressively the tumour is likely to behave. He will also be able to tell if there has been any invasion of the tumour into the muscle.

Further tests may then be necessary to determine the stage of the cancer. That is: how far it has spread. This is done by imaging. For example: chest X-ray, CT scan or MRI scan of the pelvis, intravenous pyelogram (i.e. where dye is injected into a blood vessel, and is then excreted by the kidneys. X-rays show up the kidney and bladder).

For superficial bladder cancer, the grade of the cancer is the most important prognostic indicator. For invasive bladder cancer, the stage is most important. There are four stages. Stage one is cancer that has invaded deeper than the bladder lining, but not yet into the muscle. Stage two is cancer extending into the muscle. Stage three is cancer extending right through the bladder wall or into other pelvic organs. Stage four is very advanced disease, or cancer that has spread to lymph nodes or distant organs.

Prognosis is dependent on the stage. Stage one bladder cancer has an average survival rate of 70% at five years, whereas patients with metastatic disease (stage four) rarely survive longer than six to nine months.

Treatment

Treatment for bladder cancer depends on the grade of the cancer, the stage of the cancer, the patient’s general health, and of course the patient’s wishes. Treatment is usually by a team of specialists, including a urologist and an oncologist. Treatment options include surgery, radiation therapy, chemotherapy, and immunotherapy.

Surgery

Surgery is a common form of treatment for bladder cancer. For superficial bladder cancer, treatment may be completed at the same time as diagnosis through a cystoscope. This procedure is called trans urethral resection (TUR), and involves inserting an instrument through the cystoscope to remove the entire tumour, and then burning the tumour bed with an electric current in order to remove any remaining cells (fulguration).

A pathologist then examines the removed tissue under a microscope, to determine the grade of the tumour. If it is grade three, or if this is not the first time that the tumour has been removed, then it means further treatment may be necessary to minimise the risk of the cancer becoming invasive. This would involve immunotherapy (see immunotherapy).

For more advanced bladder cancer that involves the bladder muscle, it is often necessary to remove the entire bladder. In a procedure called radical cystectomy the entire bladder, lymph nodes, and surrounding organs (which may contain cancer cells) are removed. In men, these organs include the prostate and seminal vesicles and in women, it includes the uterus, ovaries, fallopian tubes and part of the vagina.

When the bladder is removed, the urine must be collected either via a bag which is worn close to the abdominal wall on the outside of the body (this is called a stoma) or the surgeon may create a pouch inside the abdomen which collects the urine. The patient then drains the pouch periodically with a small catheter.

Occasionally only part of the bladder is removed. This is usually done for smaller tumours confined to specific areas of the bladder. After this type of surgery urination occurs normally. Unfortunately, this operation is not usually possible. In the event that only part of the bladder is removed, it may be necessary to give some radiation therapy pre-operatively.

Radiation therapy

Radiation therapy may be used pre-operatively, post operatively (for high-risk cases), in place of surgery (if surgery cannot or will not be tolerated for some reason), and to relieve symptoms in advanced cases. It may be given alone or in combination with chemotherapy.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. It may be used alone in advanced cases or, in early disease, together with surgery and/or radiation therapy. It is usually given through a drip, but certain types may be given in tablet form. It may also be given directly into the bladder. Depending on which drugs are given, treatment may be as an outpatient or as an inpatient. Your doctor will explain fully the possible side effects of the drugs that are used, but common side effects are nausea, vomiting, and a drop in blood count. The side effects are carefully monitored and pretreated if possible.

Immunotherapy (biological therapy)

Immunotherapy is a form of treatment which uses the body’s own immune system to fight the cancer. It is used for superficial bladder cancer that has been shown to be high risk, and involves the installation via a catheter of a solution of BCG (which stimulates the immune system) into the bladder following TUR. This helps to prevent the cancer from recurring. The solution is left in the bladder for about 2 hours before the patient is allowed to urinate. This is repeated once a week for about 6 weeks. More than one course may be necessary.

Clinical trials

Many centres are involved in clinical trials, and your doctor may discuss this with you. Many of the newer and more promising drugs are compared to standard treatment regimens. Often neither the doctor nor the patient is allowed to know which of the two treatments the patient is receiving until the end of the trial. These trials give patients the opportunity to be involved in cancer research, as well as possibly benefiting from the newer drugs. Cancer research is going on all the time in order to try and improve outcomes.

Side effects of treatment

Unfortunately the effects of cancer therapy cannot always be limited to cancer cells, and healthy cells may also become damaged. Side effects depend on the type and extent of treatment. They are also different in each individual. Before any cancer therapy is started, your doctor will explain fully the possible side effects of the treatment proposed.

TUR doesn’t have many side effects. Patients may have blood in the urine and pain on passing urine for a few days afterwards, but this is temporary.

Bladder removal (cystectomy) is major surgery, and patients will experience significant pain for a few days after the operation. This can be controlled with drugs. It may take up to six weeks to recover from an operation of this nature. It also takes time to get used to using and looking after the stoma. It is important that you receive counselling prior to this procedure about what to expect, and how to manage with a stoma. Regular bag changes are done, and a stoma sister will help you care for yours. Many people live for years and years with their stomas without anyone realising that they have one.

Women who have had had this operation will not be able to have children afterwards, as the uterus is removed. In addition part of the vagina is removed, which may make it narrower and shallower. This may make sexual intercourse difficult.

She will also become menopausal (if she is not so already) as the ovaries have been removed. Symptoms eg hot flushes are controllable with hormone replacement therapy.

In the past, all men who had this operation were rendered impotent, owing to nerve damage. However, improvement in surgical technique has made it possible to prevent this side effect in some cases. Even if potency is retained, however, ejaculation will not occur. This will make it impossible to father children. Sperm banking should be done if the patient wishes to father children in the future.

Radiation therapy side effects are related to the dose given, to the site treated, and the size of the area. Changes in skin colour may occur, with some “tanning” effect in the area of radiation. During treatment the patient may experience tiredness, nausea, diarrhoea, and urinary discomfort. These can be controlled with medication. In men there is a chance of impotence following radiation therapy, although this may not be an immediate effect. Women may experience vaginal dryness and difficulty with intercourse.

If a large area is being irradicated, blood counts may drop and treatment might be delayed. Counts will be checked weekly throughout the radiation.

The side effects of radiation therapy may be distressing, but are often well controlled with medication, and in most cases are temporary.

Chemotherapy side effects depend on the drugs used and the dosing schedule. Common side effects with intravenous chemotherapy are nausea and vomiting, and a drop in blood count about one week after treatment. Some drugs may cause hair loss, tingling in the fingertips or buzzing in the ears. Your doctor will fully explain to you the side effects of your particular treatment before it is given.

Drugs that are placed in the bladder may cause irritation and mild bleeding for a few days after treatment.

Biological therapy may irritate the bladder for a few days after treatment. It may also cause fever and chills, muscle aches and diarrhoea. These are temporary. With BCG there is also a small risk of the patient contracting tuberculosis, as it is this which is used to stimulate the immune system. These risks will be fully explained to you by your doctor.

Prevention

Unfortunately, there is no definite way of preventing bladder cancer. The best thing is to avoid risk factors when possible.

Don’t smoke and avoid occupational exposure to certain chemicals – follow good safety practices at work. Drink plenty of liquids – this causes more frequent bladder emptying, and limits the time during which the bladder is exposed to urine that may contain harmful substances.

Previously reviewed by Dr Jeannette Parkes, MBBCh FC Rad Onc, Consultant radiation oncologist at Groote Schuur Hospital

Reviewed by Dr David Eedes, Oncologist, March 2011