by In the last few years, Professor Syed Hussain has become increasingly concerned about the number of patients presenting with advanced stage bladder cancer.
“Since Covid, there’s been a problem with patients not getting their GP appointments,” says Professor Hussain, professor of medical oncology at the University of Sheffield and honorary consultant at Sheffield Teaching Hospitals. “And as a result, we’re seeing more cases coming in later, when their cancer becomes a life-limiting illness.”
Recent advances in diagnostics may make it easier to detect patients early. Various NHS trusts are currently evaluating a test developed by Professor Richard Bryan, director of the Bladder Cancer Research Center at the University of Birmingham, and his team called Galleas Bladder which detects signs of cancer DNA in the urine and can diagnosis of the disease with 90. percent accuracy.
So, how does bladder cancer develop and what are the most common causes?
What is bladder cancer?
Bladder cancer is defined as an abnormal cancerous growth arising from cells in the bladder. More than 90 percent of all bladder cancers are called transitional cell carcinomas, which arise from the layers of urothelial cells that line the bladder and the rest of the urinary tract. Urothelial cells are highly specialized because, unlike many of the other cells that line our internal organs, they help store fluid – in this case urine excreted by the kidneys – rather than reabsorbing it back into the body.
“The bladder is designed to be able to expand and contract without damage,” says Professor Bryan. “So the lining of the bladder is very specialized and it regenerates slowly because it doesn’t have to deal with the same amount of local trauma as the bowel, for example. But it is from this lining that bladder cancers arise.”
However, there are also some other rare forms. About 5 percent of patients have metaplastic cancers, usually caused by chronic inflammation, from chronic urinary tract infection, long-term catheter implantation in severely disabled patients or water-borne parasites. This causes normal cells to transform into different types of cells that may become cancerous.
How common is bladder cancer?
According to statistics from the charity Fight Bladder Cancer approximately 21,185 people in the UK are affected by the disease each year. “This puts it up there as a relatively common cancer, probably the fourth or fifth most common cancer in men,” says Professor Bryan.
Like many cancers, the severity depends greatly on how quickly it is caught. Professor Bryan estimates that up to 80 percent of patients are diagnosed at a stage where the cancer can still be put into remission. However, once the disease penetrates the muscle layer of the bladder, the prognosis worsens rapidly, with five-year survival rates of just 50 percent.
The different categories of bladder cancer
The vast majority of bladder cancer research has focused on transitional cell carcinomas. Most patients have non-muscle invasive cancer, where the tumors are still confined to the lining of the bladder or the layer just below it. Professor Bryan explains that they are then categorized as low risk, intermediate risk, high risk or very high risk, depending on how aggressive the cancer appears to be.
“This is determined by the number of tumors a patient has, as bladder cancers often involve multiple tumors, and also the size of the tumors,” says Professor Bryan.
However, there is also a more serious form of the disease where the tumors have progressed beyond the bladder lining and into the muscle.
What causes bladder cancer?
About half of all bladder cancers are directly linked to the ingestion of toxic chemicals called aromatic amines and polycyclic aromatic hydrocarbons, which are abundant in industrial and manufacturing plants and diesel exhaust. “If we go back to the history of bladder cancer, it has often been linked to people who have worked for many years in factories manufacturing synthetic dyes as well as tire manufacturing and rubber manufacturing,” says Professor Bryan.
However, the biggest contributor to bladder cancer is tobacco, which accounts for 40 percent of transitional cell carcinomas. Cigarette smoke is rich in aromatic amines and polycyclic aromatic hydrocarbons, which are absorbed through the lungs and into the bloodstream. The liver metabolizes these chemicals which are excreted into the bladder through the kidneys.
“They react with other components of the urine and are almost reactivated as carcinogens,” says Professor Bryan. “So you have your urine sitting in your bladder for hours afterwards, which contains potential carcinogens that can damage the DNA in those urothelial cells lining the bladder, starting the process of transformation into malignancy . If you’re a 20-day smoker and it’s been 10 years, you’re four times more likely to get bladder cancer than someone who’s never smoked.”
The other major risk factor for bladder cancer is simply being male. Three times more men develop the disease compared to women, and Professor Bryan’s research group is trying to understand why this is so, and whether it could target future therapeutic options.
“This is just speculation, but women may have some sort of genuine protection against bladder cancer,” says Professor Bryan. “It could be hormone related. It seems ultimately to be related to how the immune system works, and immune surveillance of depleted bladder cells is better in women than in men. But these are just hypotheses.”
What are the symptoms?
Oncologists estimate that between 60 percent and 80 percent of patients diagnosed with bladder cancer have visited their doctor after seeing blood in their urine, a symptom known as hematuria.
“That is a very important sign that cannot be missed,” says Professor Hussain. “Not all hematuria is going to be bladder cancer, it could also be related to urinary infections, but it could be an early sign of cancer. People who see this should see their GP and then be referred to urology services where hospitals have a one-stop clinic that does an imaging scan for anyone with haematuria.”
How is bladder cancer diagnosed?
For many years, bladder cancer has been diagnosed by flexible cystoscopy, a test in which a thin fiber optic tube is passed through the urethra and enables the doctor to look directly at the lining of the bladder.
However, this has several limitations, from discomfort for patients, to the number of trained specialists required to perform the examination. If NHS evaluations confirm that the Galeas Bladder urine test is comparable to flexible cystoscopy, it could be rolled out on a national scale.
Simon Crabb, professor of experimental cancer therapeutics at the University of Southampton, says that if urine-based tests are proven to be accurate enough, they could be used as part of screening programs in the future.
“We don’t currently have a screening test for bladder cancer,” says Professor Crabb. “A lot of early detection advice involves people recognizing blood in urine. Many patients will have something perfectly benign, but the best way at the moment is to detect it early. Bladder cancer and urine-based tests make sense, and maybe that’s the way to go.”
Any patient diagnosed with bladder cancer, even at an early stage, will need to get used to regular, ongoing surveillance. “For patients who have been treated for early bladder cancer, their management will depend on monitoring by camera inspection (cystoscopy),” says Professor Bryan. “Some patients will be getting that every three to six months, for many years.”
How is it dealt with?
There are four different stages.
Patients with early stage bladder cancer can usually be effectively managed with a type of immunotherapy called Bacillus Calmette Guérin (BCG) which is administered directly into the organ through a catheter. Professor Hussain says that in many cases this can effectively manage the cancer and put it into remission, and surgery is only considered in cases where the cancer has spread into the muscle.
In the 20 to 25 percent of patients with muscle-invasive bladder, there are two main options, chemotherapy followed by surgery or chemotherapy. The second case is an alternative to surgical removal of the bladder and involves a combination of chemotherapy and radiotherapy to sensitize the cancer cells to radiotherapy.
However, just under one in ten patients are found to have advanced or metastatic bladder cancer, which has not just entered the bladder muscle but has spread beyond the bladder into other organs.
“Here, unfortunately, treatments will not be curative but only palliative,” says Professor Hussain. “But in metastatic cancer, the treatment landscape has changed dramatically and there is much more hope. There are some new drug options, patients are living longer and staying well.”
Professor Hussain says that while the average survival rate for a patient with metastatic bladder cancer is between 12 and 18 months, this has now increased to between 24 and 30 months in the last few years, particularly with the advent of a new class of drugs which called immune checkpoint inhibitors that are given into the bloodstream through a drip. These drugs are now available on the NHS as standard of care.
Recently, clinical trials of immune checkpoint inhibitors in combination with another class of drugs called antibody-drug conjugates have shown promising results in improving survival outcomes for patients with metastatic cancer.
“You can only really give six cycles of chemotherapy, for about three to four months, because then the patient’s bone marrow starts to split,” says Professor Hussain. “But immune checkpoint inhibitors are very smart drugs, using your own immune cells to find and attack camouflaged cancer cells.”
A new clinical trial is testing whether it is safe to administer immune checkpoint inhibitors directly into the bladder in patients with early stage cancer, to see if this can treat their cancer more effectively. Professor Hussain is currently involved in a trial looking at a certain immune suppressant called atezolizumab in patients with non-muscle invasive cancer, for whom BCG has not worked, or people with muscle invasive cancer who are not well enough to undertake. chemotherapy.
“I think it’s important to highlight the hope we’re seeing,” says Professor Hussain. “Patients are living longer, and with a good quality of life, which is associated with these new drugs.”
Recommended
Why you’re at greater risk of cancer than you were 25 years ago – here’s what you should do about it
Read more
