Bladder cancer research

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than the treatments that are available at the moment
• We know they are safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in people. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.

Tests with patients are called clinical trials. There are 4 phases of clinical trials. This is fully explained in the trials and research section. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team. The database also has information about closed trials and trial results.

All the new approaches covered here are the subject of ongoing research. Until studies are completed and new effective treatments are found, these treatments cannot be used as standard therapy for bladder cancer.

Research into preventing cancer using drugs or other agents (including our diet) is called 'chemoprevention'.

People who have been successfully treated for bladder cancer are at risk of the cancer coming back in their bladder.  They could also develop another cancer. This could be in the bladder or in other parts of the urinary tract system, such as the tubes that the urine flows down (ureters) or the lining of the kidneys.

The SELENIB trial is looking at whether adding selenium or vitamin E, or both, to your diet can help to stop early bladder cancer coming back after treatment. You can find more information about bladder trials on our clinical trials database. Choose 'bladder' from the drop down menu.

Some doctors think that bladder cancer might affect the way that drugs are broken down in your body by chemicals called enzymes. It is possible that this change in enzyme activity may affect how well treatment works for people with bladder cancer. The Pittsburgh study has been looking into this. Researchers gave four different drugs to a group of people who went to clinics because they had blood in their urine. These four drugs are not cancer treatments. But the results of the study may affect the way bladder cancer is treated in the future. This study is no longer recruiting and we are waiting for the results.

Doctors are trying some new ways of diagnosing bladder tumours. They include

• New cystoscopy techniques
• Urine tests

New cystoscopy techniques

Bladder cancer is normally found by looking directly into the bladder with a camera (a cystoscopy). Some research is looking at using photodynamic diagnosis to improve the number of cancers diagnosed by cystoscopy. Before cystoscopy, your doctor puts a liquid chemical activated by light into the bladder. During the cystoscopy they shine a blue light into the bladder. Doctors hope that this procedure will show up bladder cancers more easily than normal cystoscopy. This procedure is especially useful if cancer cells have shown up in urine tests but there is no tumour in the bladder.

Doctors are testing another way to make tumours show up more clearly during cystoscopy. It is called narrow band imaging (NBI). It uses special computer enhanced cystoscopes which make the blood vessels in tumours easier to see.

Urine tests

Doctors would prefer a less invasive test than cystoscopy, but they need to prove that any new test is accurate and reliable. Doctors in the USA and UK are developing a number of urine tests that may help to pick up a new bladder cancer or one that has come back.

The Food and Drug Administration (FDA) in the USA have approved two of the new tests (the BTA test and NMP22 test). They have not replaced other ways of picking up bladder cancer. The best way to diagnose bladder cancers accurately is still cystoscopy and biopsy. But some doctors are very hopeful that they may be able to use these urine tests in the future, so that people who have had bladder cancer may not have to keep having cystoscopies.

The new tests are the

• BTA test
• NMP22 test
• Mcm5 test

BTA test

BTA stands for Bladder Tumour Associated Antigen. This test uses 2 monoclonal antibodies to pick up particular proteins in the urine. If these proteins are there, it could mean cancer cells have come back in the bladder. This test is very accurate. It needs only five drops of urine and the result takes 5 minutes.

NMP22 test

NMP22 stands for Nuclear Matrix Protein (NMP). This is a type of protein found in the nucleus of cells. Some NMPs have been found in some types of cancer cells, including the cells of the most common type of bladder cancer called transitional cell cancer (TCC). These cells release NMP22 into the urine. Most healthy people only have small amounts of NMP22 in their urine, but people with TCC often have a higher than normal level.

Mcm5 test

The Mcm5 test is a new urine test that appears to be an accurate way of picking up bladder cancer. A trial looked at the Mcm5 test to see if it helped diagnose transitional cell bladder cancer. The trial team found that the Mcm5 urine test was just as reliable and accurate as the NMP22 urine test for diagnosing bladder cancer. Using these two tests together may help improve the diagnosis of bladder cancer and future trials are being prepared to test this.

Even where these tests are available, you will still need a cystoscopy to diagnose bladder cancer for some time to come.

If you have bladder cancer that has grown beyond the innermost lining of the bladder, the usual treatment is an operation to remove the bladder (open radical cystectomy). But it is a complicated operation and people have to stay in hospital for about 3 weeks. It can cause complications in some people, such as wound infection. 

Some surgeons now remove the bladder in a different way using a type of keyhole surgery called laparoscopic or robotic cystectomy. But we don’t yet know which type of surgery is best for people with bladder cancer. The Bolero trial is looking at whether people would be willing to take part in a trial comparing the 2 types of surgery. It also hopes to find out how each type of surgery affects quality of life.

A few different clinical trials are looking into how doctors use radiotherapy to treat bladder cancer.

The SPARE trial is comparing surgery to remove the bladder with radiotherapy after chemotherapy to shrink the bladder. The trial aims to find out which treatment is the best in the long term for invasive bladder cancer. Everyone in the trial has chemotherapy as a first treatment to try to shrink the cancer because doctors think this may help to get rid of the cancer for good. The trial has closed and we are waiting for the results.

The HOT 2 trial is looking at whether using a high pressure oxygen treatment called hyberbaric oxygen (HBO) therapy can help to relieve long term side effects of having radiotherapy to the area between the hip bones (the pelvis).

Researchers have looked at using radiotherapy to help stop invasive bladder cancer from coming back after treatment.The BCON trial tried 2 different ways of increasing the amount of oxygen available to the cancer cells during radiotherapy treatment. Cancer cells are more likely to be killed by radiotherapy if they have plenty of oxygen. The researchers found that increasing oxygen levels by taking nicotinamide tablets and wearing a breathing mask for a few minutes before and during each radiotherapy treatment helped people to live longer. 

The APPLY study is looking at improving radiotherapy for bladder cancer. It is looking at using a new type of CT scanning to improve radiotherapy treatment for people with invasive bladder cancer. This new type of CT scanning is called a Cone beam CT scan and is taken when you have your radiotherapy treatment. The researchers want to use the Cone beam CT scan pictures taken before each treatment to make sure that they can choose the best treatment on that day.The aim of this study is to see if using the Cone beam CT scanning can improve the radiotherapy treatment given to people with invasive bladder cancer.

The IDEAL trial is looking at using a combination of 3 different ways to plan radiotherapy to improve the treatment for bladder cancer. The doctors hope to be able to target the cancer more accurately and give a higher dose of radiotherapy than they are normally able to. The trial uses gold seeds placed around the bladder tumour combined with a cone beam CT scan, and an MRI scan to plan the radiotherapy. 

You can look for other clinical trials on our clinical trials database. Choose 'bladder' from the dropdown menu of cancer types.

Many clinical trials are under way to test new combinations of chemotherapy drugs. Doctors continue to study different combinations, different doses, or different sequences of giving the drugs. The aim of this type of research is to find better ways of treating bladder cancer with chemotherapy. Some of the chemotherapy drugs being used in trials include

• Gemcitabine
• Mitomycin C
• Cisplatin
• Carboplatin
• Fluorouracil (5FU)
• Oxaliplatin
• Methotrexate
• Vinblastine
• Paclitaxel (Taxol)
• Vinflunine (Javlor)

You can click on the links above to find out more about the side effects of these drugs. The EORTC 30986 trial compared gemcitabine and carboplatin with the combination of methotrexate, vinblastine and carboplatin for people with advanced bladder cancer. You can see the results on the clinical trials database. Tick the box for trial results and pick 'bladder' from the dropdown box of cancer types.

Another trial called BA 11 (EORTC 30987) looked at adding paclitaxel to cisplatin and gemcitabine chemotherapy for bladder cancer and other types of cancers of the urinary system. The early results of the trial showed that the cancer had shrunk or disappeared in more people who had all 3 drugs than in people who had just 2.

A trial looked at a new chemotherapy drug called vinflunine and found that adding it to standard care for people with advanced bladder cancer helped people to live longer. But it also gave quite severe side effects. In early 2010 it was licensed in Europe for people who have advanced transitional cancer and have had other treatments which are no longer working.  The Scottish Medicines Consortium (SMC) in early 2011 did not recommend that it should be available within the NHS in Scotland. They said it was not cost effective. 

Now a phase 3, randomised trial is looking at whether adding vinflunine to gemcitabine treatment works better than gemcitabine alone for people who can't have cisplatin due to poor kidney function. This trial is giving these treatments as first line chemotherapy. It has closed and we are waiting for the results.

The GO-80 study is looking at combining gemcitabine with oxaliplatin, instead of cisplatin for transitional cell cancer that has spread. Oxaliplatin is similar to cisplatin but is less likely to damage the kidneys. So doctors hope that it will work as well at controlling the cancer but may cause less side effects.

Other trials have looked at when to give chemotherapy. The EORTC 30994 trial is comparing giving chemotherapy immediately after removing the bladder with keeping chemotherapy in reserve in case the cancer comes back. This trial is no longer recruiting patients, and we are waiting for the results.

The ADVICE trial is looking at what happens to the cancer cells in people with invasive bladder cancer when they have chemotherapy or radiotherapy before surgery. The chemotherapy drugs in this trial are gemcitabine and cisplatin. The researchers want to try to find out why chemotherapy works well for some people, and less well for others. This trial is no longer recruiting patients, and we are waiting for the results. 

You can find more information about these trials on our clinical trials database. Select 'bladder' from the dropdown menu.

The BC2001 trial found that having chemotherapy at the same time as radiotherapy for bladder cancer that had spread into the muscle helps to reduce the risk of the cancer coming back, without causing more long term side effects. 

Giving chemotherapy at the same time as radiotherapy is called chemoradiation, or concurrent chemotherapy and radiotherapy. A phase 2 trial has looked at giving gemcitabine at the same time as radiotherapy for invasive bladder cancer. The researchers found that giving radiotherapy and gemcitabine together worked well to treat people with invasive bladder cancer.

Doctors often give treatment directly into the bladder to try to reduce the chances of early stage bladder cancer coming back. Researchers have been looking at ways of improving this type of treatment. One technique being studied is heating the wall of the bladder with a microwave probe, at the same time as putting in the chemotherapy drug mitomycin C. The probe and the chemotherapy are passed into the bladder through a catheter. This is known as hyperthermic mitomycin, intravesical microwave hyperthermia with intravesical chemotherapy, or the Synergo technique.

This heat treatment appears to make the cancer cells more sensitive to the chemotherapy and doctors hope this will make the chemotherapy work better and improve results. The National Institute for Health and Clinical Excellence (NICE) have announced that this procedure could be used, either before or after surgery, for bladder cancer that has not grown further than the bladder lining. But it can only be done as a part of clinical research. NICE say there is not enough evidence for how well this procedure works to make it more widely available. This treatment has sometimes worked well for people with high grade, early bladder cancer after BCG treatment into the bladder has not worked. It may help people in this situation to avoid having their bladder removed. 

The HYMN trial is looking at standard treatment and hyperthermia for people with early stage transitional cell bladder cancer. It is recruiting people whose bladder cancer has come back after initial treatment. The aim of the trial is to compare standard treatment with hyperthermia and mitomycin C chemotherapy to see which is better at controlling cancer growth. 

Doctors are trying to help make chemotherapy into the bladder for early cancer work better by using an electrical current. The idea is that the current makes it easier for the bladder lining to absorb the chemotherapy. This is called electrically stimulated intravesical chemotherapy, or electromotive drug administration (EDMA). The National Institute for Health and Clinical Excellence (NICE) have announced that this procedure could be used, either before or after surgery, for early (superficial) bladder cancer. But it can only be done as part of a clinical trial, because we don't yet have enough evidence to really know how well this works. Doctors mainly use this treatment for high grade, early bladder cancers after other treatments into the bladder have not worked.

Biological therapy uses natural body substances, or drugs developed from them, to fight cancer. There is a separate section about biological therapies. Biological therapies being researched for bladder cancer include

• Interferon
• Sunitinib
• Sorafenib
• Lapatinib
• Pazopanib
• Cetuximab
• New drugs

Interferon

Research has been looking at interferon in combination with low doses of the commonly used bladder cancer treatment, BCG. Results from early phase trials show that interferon can help to slow down or stop cancer from coming back again in people whose cancer has already come back after previous BCG treatment.

Sunitinib

Sunitinib (Sutent) is a drug used to treat some types of kidney cancer. Researchers believe it may also work for transitional cell cancer of the bladder. The SUCCINCT trial is looking at combining sunitinib (Sutent) with GC chemotherapy for transitional cell cancer of the urinary system. This includes the lining of the bladder, the pelvis of the kidney, or the tube that links the two (the ureter). The trial is for people whose cancer is locally advanced or has spread to another part of their body. It aims to find out whether adding Sutent to GC chemotherapy works better than GC chemotherapy alone and to find out which side effects it causes.

Sorafenib

Sorafenib is also called Nexavar. Some early phase trials in Europe and America are looking at how well combination treatment (with gemcitabine, cisplatin, and sorafenib) works in people with advanced bladder cancer or cancer that has spread.

Lapatinib

The LaMB trial is looking at lapatininb (Tyverb) after chemotherapy for people with bladder cancer that has spread. You may be able to join this trial if you have advanced bladder cancer which has responded to chemotherapy. And your cancer cells must have a large number of HER1 or HER2 receptors, or both. These are proteins found on the surface of some cancer cells. Lapatinib attaches to cells that have HER1 or HER 2 receptors, stopping them from telling the cells to grow. Doctors hope that the lapatinib can control the cancer for longer.

Pazopanib

The PLUTO trial is looking at pazopanib for transitional cell cancer of the urinary system that did not go away or has come back after chemotherapy. The aims of this trial are to see if pazopanib is better at treating this type of cancer than the chemotherapy drug paclitaxel, and to learn about the side effects.

Cetuximab

Cetuximab is a type of monoclonal antibody. It is already being used to treat bowel cancer and head and neck cancers. And it is being looked at in trials for several other types of cancer. The TUXEDO trial is an early trial looking at cetuximab with radiotherapy and chemotherapy for bladder cancer that has grown into the muscle layer (invasive bladder cancer).

New drugs

There is a study looking at a new drug called TKI258 to treat transitional cell cancer that has spread into the surrounding tissue (is locally advanced), or to another part of the body. TKI258 is a type of biological therapy called a tyrosine kinase inhibitor (TKI). Tyrosine kinase is a chemical messenger (an enzyme) that sends messages to cells to tell them to grow and divide. Blocking the effect of tyrosine kinase may stop cancer cells from growing and spreading. The aims of this study are to find out if TKI258 can help people with advanced transitional cell cancer and what side effects it may cause.

The BOXIT trial is looking into whether adding a drug called celecoxib to standard treatment for superficial transitional cell bladder cancer helps to stop the cancer coming back. Celecoxib is a type of non steroidal anti inflammatory drug known as a COX 2 inhibitor. These drugs block the action of a protein that may help cancers to grow. 

You can look for other clinical trials on our clinical trials database. Select 'bladder' from the drop down menu.