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Bladder cancer

Introduction

Cancer of the bladder is a fairly common type of cancer. The most common symptom of bladder cancer is passing blood in your urine.

The bladder

The bladder is a hollow, balloon-like organ that is located in the pelvis and is designed to store urine.

The kidneys filter waste products out of your blood. The waste products are mixed with water to create urine. The urine is passed out of your kidneys and into your bladder through two tubes that are known as the ureters.

When your bladder is full, the urine passes out of the bladder through another tube called the urethra, before then being passed out of the vagina (women) or penis (men) upon urination.

Types of bladder cancer

Bladder cancer can be classified in two different ways:

• according to the type of bladder cells the cancer begins in, and
• according to how far the cancer has spread when it is first diagnosed.

Bladder cancer by cell type

The most common type of bladder cancer is known as transitional cell carcinoma (TCC), which is responsible for 90% of all cases of bladder cancer. TCC is cancer that starts in the inner lining of the bladder.

The lining of the bladder is known as the transitional epithelium.

Less common types of bladder cancer include:

• squamous cell bladder cancer - which is cancer that starts in the upper lining of the bladder, and accounts for 2% of all cases, and
• adenocarcinoma of the bladder - which is cancer that starts in specialised cells in the lining of the bladder that are responsible for producing mucus. This type of bladder cancer is responsible for between 1-2% of all cases.

Bladder cancer by spread

There are two main ways that bladder cancer can be classified according to how far it has spread:

• non-invasive bladder cancer (also known as superficial bladder cancer) - is a term that is used to describe cases of bladder cancer that have not spread beyond the lining of the bladder, and
• muscle invasive bladder cancer (sometimes simply known as invasive bladder cancer) - is a term that is used to describe cases of bladder cancer that have spread beyond the lining of the bladder and into the surrounding muscles.

An estimated 70% of cases are diagnosed as non-invasive bladder cancer, and the remaining 30% are diagnosed as muscle invasive bladder cancer.

How common is bladder cancer?

Bladder cancer is the seventh most common cancer in the UK, with an estimated 10,000 new cases diagnosed every year.

Men are twice as likely to develop bladder cancer than women.

The risk of developing bladder cancer increases the older a person becomes, with 80% of cases occurring in people who are over 65 years of age.

In the UK, an estimated 3,300 men and 1,600 women die each year as a result of bladder cancer.

Smoking is the leading risk factor for bladder cancer which is thought to be responsible for 50% of all cases of bladder cancer.

Outlook

The outlook for non-invasive bladder cancer is very good. A cure is usually achievable and 90% of people will live for at least five years after receiving a diagnosis, with many living much longer.

The outlook for muscle-invasive bladder cancer is less favourable because achieving a complete cure is often not possible. An estimated 50% of people with muscle-invasive bladder cancer will die within five years of receiving a diagnosis.

Treatment for bladder cancer includes radiotherapy, chemotherapy, and surgery.

Symptoms

Blood in your urine (hematuria) is the most common symptom of bladder cancer.

Other symptoms of bladder cancer usually involve a change in your normal pattern of urination, such as:

• a need to urinate on a more frequent basis,
• having a sudden urge to urinate, and
• experiencing pain, usually a burning sensation, when passing urine.

Less common symptoms of bladder cancer include:

• pelvic pain,
• bone pain,
• unexplained weight loss, and
• swelling of the legs.

When to seek medical advice

You should always visit your GP if you notice blood in your urine. It is highly unlikely to be the result of bladder cancer as only 1 in 1,250 cases of hematuria are caused by bladder cancer.

However, blood in your urine is a symptom that you should never ignore, and it always requires further investigation.

Causes

How does cancer begin?

Cancer begins with a change in the structure of the deoxyribonucleic acid (DNA) that is found in all human cells. DNA provides cells with a basic set of instructions, such as when to grow and when to reproduce.

A change in the DNA's structure (a genetic mutation) changes these instructions so that the cells carry on growing and reproducing uncontrollably. This produces a lump of tissue that is known as a tumour.

How does cancer spread?

Left untreated, bladder cancer will spread from the lining of the bladder into the surrounding muscles. Once the cancer has reached the muscles it is able to spread to other parts of the body, usually through the lymphatic system.

The lymphatic system is a series of glands (or nodes) that are located throughout your body. It is similar to the blood circulatory system. Lymph glands produce many specialised cells that are needed by your immune system to fight infection.

Once the cancer reaches the lymphatic system, it can spread to any other part of the body, including your bones, blood, and organs. The spread of cancer to other parts of the body is known as metastasis.

Risk factors Smoking

Smoking is the single biggest risk factor for bladder cancer. This because tobacco contains over 40 different types of carcinogenic (cancer-causing) chemicals.

If you smoke for a prolonged period of time (many years) the carcinogenic chemicals will pass into your urine and will begin to coat the lining of your bladder. This can then cause genetic mutations which lead to the development of bladder cancer.

It is estimated that between 50-65% of bladder cancer cases in men, and between 20-30% of cases in women, are caused by smoking.

Occupational exposure to chemicals

The second biggest risk factor for bladder cancer is occupational exposure to chemicals, which accounts for 10% of all cases.

Chemicals that are known to increase the risk of bladder cancer include:

• aniline dyes,
• 2-Naphthylamine,
• 4-Aminobiphenyl,
• xenylamine, and
• benzidine.

Occupations that have been linked to an increased risk of bladder cancer are manufacturing jobs that involve the following substances:

• rubber,
• dyes,
• textiles,
• plastic, and
• chemicals.

The link between these types of occupations and bladder cancer was discovered during the 1970s and 1980s. Since then, the regulations relating to exposure to cancer-causing chemicals have been made much more rigorous, and many of the above chemicals have been banned. Therefore, in the future, the number of occupation-related cases of bladder cancer should begin to fall.

However, at the moment, the number of occupation-related cases of bladder cancer remains moderately high. This is because it can take up to 25 years after initial exposure to the chemicals before bladder cancer starts to develop.

Other risk factors

Other risk factors for bladder cancer include:

• receiving previous radiotherapy treatments, and
• the long-term use of a catheter (a tube that is used to empty the bladder).

   

Diagnosis

Initial testing

If you notice blood in your urine, your GP will ask you to provide a urine sample. The sample will then be sent to a laboratory to be tested for the presence of abnormal cells that could be due to the presence of bladder cancer. This test is known as urinary cytography.

It should be stressed that urinary cytography is not 100% accurate. It can sometimes detect abnormal cells when there no cancer is present (a false-positive result) or alternatively, it can fail to detect abnormal cells when cancer is present (a false-negative result). Therefore, urinary cytography is an aid to diagnosis but it is not a definitive diagnosis in itself.

Your urine will also be tested for the presence of bacteria in case your symptoms are due to an infection.

Your GP will also carry out a physical examination of your rectum (back passage), and your vagina (for women). This is because in some cases of bladder cancer it is possible to feel a noticeable lump that presses against the rectum and vagina.

If the results of these initial testing are inconclusive, or a diagnosis of bladder cancer is suspected, it is likely that you will be referred to an urologist for further testing. A urologist is an expert in treating conditions that affect the urinary system.

Confirming the diagnosis Intravenous urogram (IVU)

An intravenous urogram (IVU) is a test that is used to determine whether there are any abnormalities in your urinary system (your bladder, kidneys, and uterus). An IVU can sometimes help to confirm a diagnosis of bladder cancer, or uncover an alternative cause of your symptoms, such as bladder stones.

Before the IVU takes place, you will be injected with a special dye that shows up on X-ray. The radiologist (a specialist in using medical imaging technology, such as X-rays) will study how the dye moves through your urinary system in order to see if there are any problems.

You may experience a metallic taste in your mouth and flushed, itchy skin when the dye is injected. This is normal and the symptoms will pass in a few minutes.

Cystoscopy

A cystoscopy is a procedure that uses a special instrument, called a cystoscope, to examine the inside of your bladder. The procedure usually takes between 5-10 minutes to perform.

A cystoscope is a thin, flexible telescope (viewing tube) that is passed into your body and allows the urologist to look inside your bladder.

During a cystoscopy, jelly containing a local anaesthetic is squirted into the opening of your urethra (the tube that runs from the penis, or vagina, to the bladder, which urine passes through when you urinate). As well as working as a painkiller, the jelly helps the cystoscope to pass into the urethra more easily.

The urologist will study the lining of your bladder and urethra in order to identify any abnormal areas that could be the result of bladder cancer.

Biopsy

If any abnormalities are found in your bladder during a cystoscopy, it is likely that you will be asked to come back so that a sample of bladder tissue can be removed for further testing. This is known as a biopsy.

A sample of bladder tissue will be taken using a more rigid type of cystoscope as it is necessary to pass small surgical instruments up through the cystoscope in order to remove the sample. As this procedure can be uncomfortable, you will be given a general anesthetic.

Further testing

If the results of your biopsy show that there are cancerous cells in your bladder lining, you may be referred for a series of further tests in order to determine whether the cancer has spread beyond the lining of your bladder and, if so, how far it has spread.

These tests can include:

• chest X-rays,
• computer topography (CT) scan,
• a magnetic resonance imaging (MRI) scan, and
• a bone scan.

A bone scan involves a small amount of radioactive material being injected into your veins. Abnormal areas of bone will absorb the material at a faster rate than normal bone. Therefore, any abnormal areas of bone that may be affected by cancer will show up as 'hot-spots' on the scan.

Treatment

Cancer treatment team

Many primary care trusts (PCTs) have multi-disciplinary teams (MDTs) that treat bladder cancer. See box, left.

If you have bladder cancer, you may see several, or all, of these healthcare professionals, as part of your treatment.

Deciding what treatment is best for you can be difficult. Your cancer team will make recommendations, but the final decision will be yours.

Before going to hospital to discuss your treatment options, you may find it useful to write a list of questions to ask the specialist. For example, you may want to find out what the advantages and disadvantages of particular treatments are.

Non-invasive bladder cancer Your treatment plan

Your recommended treatment plan will depend on whether your MDT feels that there is a low, moderate, or high risk of the cancer returning and/or spreading beyond the lining of your bladder. This risk is calculated using a series of factors. These include:

• the number of tumours that are present in your bladder,
• whether the tumours are larger than 3cm (1 inch) in diameter,
• whether you have had previous episodes of bladder cancer,
• whether the tumours are limited to your bladder lining, or whether they have started to spread to the tissue beyond the lining, and
• the grade of the cancer cells.

The grade of the cancer cells describes how aggressively they are likely to grow and spread, with low grade being the least aggressive and high grade being the most aggressive.

If the risk of your cancer returning and/or spreading is low, your recommended treatment plan will usually be surgery to remove the tumours followed by a course of chemotherapy.

If the risk of your cancer returning and/or spreading is moderate, you will be given a longer course of chemotherapy after surgery.

If the risk of your cancer returning and/or spreading is high, as well as surgery and chemotherapy, you will be given an additional medication called the Bacillus Calmette-Guérin (BCG) vaccine.

Surgery

The standard surgical treatment for non-invasive bladder cancer is known as a transurethral resection of a bladder tumour (TURBT). In most cases, a TURBT can be performed at the same time as a biopsy.

A TURBT is performed under general anaesthetic. The surgeon will use a cystoscope to find all the visible tumours and will then cut them away from the lining of the bladder using instruments that are passed down through the cystoscope.

Once the tumour(s) have been removed, any bleeding can be stopped using a mild electric current to cauterise (seal with heat) the remaining wound.

If you experience significant bleeding, a thin, flexible tube, known as a catheter, may be inserted into your urethra and directed up into your bladder. The catheter will be used to drain away any blood and debris from your bladder, and it may need to be kept in place for several days.

After having a TURBT, most people are able to leave hospital within 48 hours, and are able to resume normal physical activity within two weeks.

Chemotherapy

Once a TURBT is complete, you will be given one, or more, courses of chemotherapy. The first course of chemotherapy will be given immediately after surgery once you have recovered from the effects of the general anaesthetic.

A type of chemotherapy that is known as intravesical chemotherapy is used. It involves placing a liquid solution of chemotherapy medication directly into your bladder by way of a catheter. The solution will be kept in your bladder for about a hour before being drained away.

There may be some residue of the chemotherapy medication left in your urine, so when going to the toilet it is important not to splash yourself, or the toilet seat, with urine as it could irritate your skin. After passing urine, you should also wash the skin around your genitals with soap and water. Your cancer nurse will be able to provide you with more advice about these issues.

The advantage of this technique is that as the chemotherapy medication is only in your bladder, and because it is not injected into your blood (intravenous chemotherapy), you will not experience the side effects that are most commonly associated with chemotherapy, such as nausea, fatigue, and hair loss.

The most common side effect of intravesical chemotherapy is irritation and inflammation of the bladder lining. This can cause:

• a frequent need to urinate, and
• pain when urinating.

These side effects should pass within a few days.

If your cancer is low-risk, you should not require any additional treatment. However, if your cancer is medium or high risk, you will be given additional courses of chemotherapy, usually once a week, over the course of six weeks.

It is important that you use contraception while you are having intravesical chemotherapy because the medication that is used can temporarily affect the quality of a man's sperm and a woman's eggs, increasing the risk of birth defects.

Bacillus Calmette-Guérin (BCG) vaccine

The Bacillus Calmette-Guérin (BCG) vaccine is used to treat high-risk cases of non-invasive bladder cancer in order to reduce the risk of the cancer returning.

The BCG vaccine was originally designed to treat tuberculosis (TB) but it has also proved to be an effective treatment against bladder cancer. Exactly how the BCG vaccine works is still unclear. It appears to stimulate the immune system in such a way that the immune system begins to target and destroy any remaining cancer cells.

The BCG vaccine is administered in the same way as intravesical chemotherapy. A liquidised version of the vaccine is passed into your bladder. You will need to keep the vaccine in your bladder for two hours after which it is drained away.

The precautions regarding not splashing yourself, or the toilet seat, with urine also apply to the BCG vaccine.

Most people require six courses of treatment given weekly over the space of six weeks. Depending on your circumstances, maintenance therapy may also be recommended. This involves you receiving further doses of the BCG every six months, with a series of three weekly doses. Maintenance therapy usually lasts for three years.

Common side effects of the BCG include:

• a frequent need to urinate,
• pain when urinating, and
• blood in your urine

Less common side effects include:

• a high temperature (fever) of above 39C (102.2F),
• skin rash, and
• a general sense of feeling unwell.

You should inform your MDT if the side effects become troublesome because additional treatments for them are available.

Invasive bladder cancer Your treatment plan

The recommended treatment plan for invasive bladder cancer will depend on how far the cancer has spread.

Health professionals use a staging system to describe the spread of bladder cancer. The stages are outlined below.

• T2a - where the cancer has spread to the inner half of the muscles surrounding the bladder.
• T2b - where the cancer has spread to the outer half of the muscles.
• T3a - where the cancer has spread into the layer of fat surrounding the muscle, but can only be seen with a microscope.
• T3b - where the cancer has spread into the layer of fat surrounding the muscle and can be seen without using a microscope.
• T4a - where the cancer has spread beyond the bladder into near-by organs, such as the prostate, vagina, or womb.
• T4b - where the cancer has spread to the wall of the pelvis or abdomen.

In cases of T2, T3 and T4a bladder cancer, a cure may be possible using a combination of chemotherapy and radiotherapy, plus surgery to remove some, or all, of the bladder.

In cases of T4b bladder cancer, unfortunately the prospect for a cure is slim. However, it is possible to control the symptoms and slow the spread of the cancer using chemotherapy and radiotherapy and, in some cases, surgery.

Surgery

Surgery for invasive bladder cancer involves removing some, or all, of the bladder. This is known as a cystectomy.

Cystectomy

There are two types of cystectomy:

• a partial cystectomy - where only part of the bladder is removed, and
• a radical cystectomy - where all of the bladder is removed as well as near-by lymph nodes, part of the urethra, the prostate (in men), and the cervix and womb (in women).

A radical cystectomy carries the obvious drawback of the loss of normal bladder function. Further surgery will be required to compensate for the loss of bladder function by creating an alternative way for urine to leave your body. This type of surgery is known as urinary diversion.

Men also have the risk of not being able to get or maintain an erection (erectile dysfunction) after a radical cystectomy because the operation can sometimes damage the nerves that are responsible for this ability. However, treatments are available for erectile dysfunction.

More information about urinary diversion and erectile dysfunction is provided in the complications section.

The main advantage of a radical cystectomy is that is has a greater track record of success in preventing the return of the cancer and extending life-span. Therefore, it is usually the treatment of choice for invasive bladder cancer.

An exception may be made in cases of T2a and T2b bladder cancer where there is only one tumour present in the bladder.

You should discuss the advantages and disadvantages of both techniques with your MDT before making a decision about your treatment.

Radiotherapy

Radiotherapy is a type of treatment that uses pulses of radiation to destroy cancerous cells.

There are three main ways that radiotherapy can be used to treat bladder cancer which are explained below.

• Radiotherapy can be used before a cystectomy is carried out in an attempt to shrink the tumour(s) in order to increase the chances of the operation being successful.
• Radiotherapy can be used as a primary treatment to try to cure bladder cancer; this may be a preferred option if your general state of health is thought to be too poor to withstand the effects of a cystectomy.
• Radiotherapy can be used to help control symptoms in cases of incurable bladder cancer; this is known as palliative radiotherapy.

External radiotherapy

Radiotherapy that is used to shrink tumours and/or to achieve a cure is given by a machine that beams the radiation at the bladder. This is known as external radiotherapy.

Sessions of external radiotherapy for bladder cancer are usually given on a daily basis, for five days a week, over the course of 4-7 weeks. Each session of radiotherapy lasts about 10-15 minutes.

As well as destroying cancerous cells, radiotherapy can also damage healthy cells so it can cause a number of different side effects. These include:

• diarrhoea,
• an increased need to urinate,
• pain when urinating,
• tightening of the vagina (in women) which can make having sex difficulty and painful,
• erectile dysfunction (in men),
• loss of pubic hair, and
• infertility.

With the exception of infertility, these side effects should pass a few weeks after your treatment finishes. The fact that radiation has been directed at your pelvis usually means that you will be infertile for the rest of your life. If you still want to have children you should discuss possible treatment options with your MDT

For example, men can have samples of their sperm frozen and women can have their eggs frozen for use in future artificial insemination treatments such as IVF. However, this will not be possible if you are a woman and you have a radical cystectomy because your womb will be removed.

External radiotherapy will not make you radioactive, and you will pose no danger to other people, including children and pregnant women.

Palliative radiotherapy

Palliative radiotherapy is usually only given for a few minutes, so it will not usually cause side effects or, if there are any side effects, they will only last for a short time.

Chemotherapy

There are three main ways that chemotherapy can be used to treat invasive bladder cancer:

• it can be used before radiotherapy and surgery in order to shrink the size of any tumours,
• it can be used in combination with radiotherapy before surgery - this is known as chemoradiation, and
• it can be used to slow the spread of incurable, advanced bladder cancer.

As yet, there is not enough evidence to say whether chemotherapy is an effective treatment when it is given after surgery in order to prevent the return of the cancer.

Intravenous chemotherapy is used to treat invasive bladder cancer, which involves a combination of different chemotherapy medications being injected directly into your vein.

Chemotherapy is usually given for two days a week, for several weeks, and then you have a week off to allow your body to recover from the effects of the treatment. This cycle is then repeated.

A total course of chemotherapy can last for up to six months. As the chemotherapy medication is being injected into your blood, you will experience a wider range of side effects than if you were having intravesical chemotherapy.
The side effects of chemotherapy can include:

• nausea,
• vomiting,
• hair loss,
• lack of appetite, and
• tiredness.

You should immediately report any signs of your infection to your MDT - for example:

• if your temperature rises above 38C (100.5f), or
• you suddenly start to feel unwell.

   

Complications

Urinary diversion

If your bladder is removed during a radical cystectomy, an alternative way of passing urine out of your kidneys will need to be found.

There are a number of different treatment options, which are described below. In some cases, you may be able to make a choice based on your personal preferences. However, certain treatment options will not be suitable for everyone.

Your MDT will be able to provide you with information about which option (or options) are suitable for you.

Urostomy

A urostomy is the most common type of urinary diversion operation. During the operation, the surgeon will make a hole in your abdominal wall. This hole is known as a stoma.

A small section of your small bowel will be removed and connected to your ureters (the two tubes which, in normal circumstances, carry urine out of the kidneys).

The other end of the small bowel will be connected to your stoma. A flat, water-proof pouch is then connected to the stoma to collect the urine.

After the operation, you will be introduced to a stoma nurse. The nurse will teach you how to care for your stoma and how and when to change the collection pouch.

Most people need to empty their pouch the same number of times a day that they would usually pass urine.

If you would like more information about living with a colostomy, you can visit the website of the Urostomy Association, which is a support group for people with urostomies.

Continent urinary diversion

A continent urinary diversion is a similar sort of operation to an urostomy, except that you will not be required to use a collection pouch.

A section of your bowel will be used to create an internal pouch that is used to store your urine. The pouch will then be connected to your ureters at one end, and to a stoma that is made in your abdominal wall at the other end.

You can empty the pouch by inserting a catheter (a thin, flexible tube) into the stoma and use it to drain away the urine. Most people need to empty their pouch about 4-5 times a day.

Bladder reconstruction

In some cases, it may be possible to create a 'new bladder', known as a neobladder. This can be done by removing a section of your bowel and reconstructing it into a balloon-like sac, before connecting it to your urethra at one end and your ureters at the other end.

Bladder reconstruction is not a suitable treatment for everyone. For example, it cannot be used if the cancer has spread to your urethra because your urethra will have to be removed during surgery.

You will be taught how to empty your neobladder by relaxing the muscles in your pelvis, while at the same time tightening the muscles in your abdomen.

Your neobladder will not contain the same types of nerve endings as a real bladder so you will not get that distinctive sensation that tells you that you need to pass urine. Some people experience a feeling of fullness inside their abdomen while other people have reported that they feel like they need to pass wind.

Due to the loss of normal nerve function, around 20-30% of people with a neobladder will experience some episodes of incontinence (the involuntary passing of urine) which usually occur during the night when they are sleeping.

It may be useful to empty your neobladder at set times each day, and then once more before you go to sleep because this may help to prevent incontinence.

The Christie NHS Foundation Trust has produced a useful booklet that provides more information about living with a neobladder.

Erectile dysfunction

You should contact your GP if you lose the ability to obtain and/or maintain an erection. It may be possible for you to be treated with a type of medicine known as phosphodiesterase type 5 inhibitors (PDE5). PDE5s work by increasing the blood supply to your penis.

The most commonly used PDE5 is sildenafil (Viagra). However, other PDE5s are available if sildenafil is not effective.

An alternative to PDE5s is a device called a vacuum pump. A vacuum pump is a simple tube that is connected to a pump. You place your penis in the tube and then pump out all the air. This creates a vacuum which causes the blood to rush to your penis. You then place a rubber ring around the base of your penis, which keeps the blood in place allowing you to maintain an erection for around 30 minutes.

Prevention

Smoking

If you are a smoker, giving up is the best way to reduce your risk of developing bladder cancer.

The NHS Smoking Helpline can offer you advice and encouragement to help you quit smoking. You can call on 0800 022 4 332, or visit the NHS Go Smokefree website.

Your GP, or pharmacist, will also be able to provide you with help and advice about giving up smoking.

Diet

There is some limited evidence to suggest that a diet that is high in fruit and vegetables and low in fat can help prevent bladder cancer.

Even if the evidence for the prevention of bladder cancer is limited, adopting such a diet is a good idea because it can help prevent other types of cancer, such as bowel cancer, as well as other serious health conditions, such as high blood pressure (hypertension), stroke, and heart disease.

A low-fat, high-fibre diet is recommended, including plenty of fresh fruit and vegetables (five portions a day) and whole grains. You should limit the amount of salt that you eat to no more than 6g (0.2oz) a day because too much salt will increase your blood pressure. 6g of salt is about one teaspoonful.

There are two types of fat - saturated and unsaturated. You should avoid foods that contain saturated fats because they will increase your cholesterol levels.

Foods that are high in saturated fat include:

• meat pies,
• sausages and fatty cuts of meat,
• butter,
• ghee (a type of butter that is often used in Indian cooking),
• lard,
• cream,
• hard cheese,
• cakes and biscuits, and
• foods that contain coconut, or palm oil.

However, a balanced diet should include a small amount of unsaturated fat, which will actually help to reduce your cholesterol levels.

Foods that are high in unsaturated fat include:

• oily fish,
• avocados,
• nuts and seeds,
• sunflower, rapeseed, olive and vegetable oils.

Recent research carried out in Sweden in 2008 suggested that a diet that is high in low-fat yogurt may also help to reduce cholesterol levels.

References

European Association of Urology. Guidelines on Bladder Cancer - Muscle-invasive and Metastatic. 2006

European Association of Urology. Guidelines on TaT1(Non-muscle invasive) Bladder Cancer. 2006

Larsson SC, Andersson S-O, Johansson J-E and Wolk A. Cultured milk, yogurt, and dairy intake in relation to bladder cancer risk in a prospective study of Swedish women and men. American Journal of Clinical Nutrition 2008; 88: 1083-1087

Mickisch, GH. Partial Cystectomy for Invasive Bladder Cancer. European Urology Supplements 4 (2005) 67-71

NICE. Improving Outcomes in Urological Cancers. 2002

SIGN. Management of transitional cell carcinoma of the bladder - a national clinical guideline. 2005

van der Meijden APM, et al. Maintenance Bacillus Calmette-Guerin for TaT1 Bladder Tumors Is Not Associated with Increased Toxicity: Results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. European Urology 44 (2003) 429-434