Over the last few years, Professor Syed Hussain has become increasingly concerned about the increasing number of patients presenting with advanced-stage bladder cancer.
“There has been a problem since Covid with patients not being able to get GP appointments,” says Prof Hussain, professor of medical oncology at the University of Sheffield and honorary consultant at Sheffield Teaching Hospitals. “And as a result, we see more cases coming later as cancer becomes a life-limiting disease.”
A recent breakthrough in diagnostics could make it easier to identify patients early. Several 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 Galeas Bladder, which detects signs of cancerous DNA in urine and can diagnose the disease 90% of the time. percent accuracy.
So how does bladder cancer develop and what are its most common causes?
What is bladder cancer?
Bladder cancer is defined as abnormal cancerous growths arising from cells in the bladder. More than 90 percent of all bladder cancers are known as 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 particularly specialized because, unlike many other cells lining our internal organs, they help store fluid (in this case, urine excreted from the kidneys) rather than taking it back into the body.
“The bladder is designed to expand and contract without being damaged,” says Prof Bryan. “So the bladder lining is highly specialized and regenerates slowly because it doesn’t have to deal with the same amount of local trauma as the bowel, for example. But that lining is where bladder cancers arise.”
But there are other rare forms. About 5 percent of patients have metaplastic cancers caused by chronic inflammation from chronic urinary tract infection, long-term catheter implantation for severely disabled patients, or waterborne parasites. This causes normal cells to turn into different types of cells that can develop into cancer.
How common is bladder cancer?
According to statistics from the charity Fighting Bladder Cancer, around 21,185 people in the UK are diagnosed with the disease every year. “This makes it a fairly common cancer and probably the fourth or fifth most common cancer in men,” says Prof Bryan.
Like many cancers, its severity depends largely on how quickly it is caught. Prof Bryan estimates that up to 80 per cent of patients are diagnosed at a stage when their cancer can still be sent into remission. However, once the disease penetrates the bladder muscle layer, the prognosis deteriorates rapidly, with a five-year survival rate of only 50 percent.
Different categories of bladder cancer
The majority of bladder cancer research has focused on transitional cell carcinomas. Most patients have cancer that has not spread to the muscle, with tumors either still confined to the bladder lining or the layer just below it. Prof Bryan explains that depending on how aggressive the cancer appears, they are classified as low risk, intermediate risk, high risk or very high risk.
“This is determined by the number of tumors the patient has, as bladder cancers often involve more than one tumor and also depends on the size of the tumours,” says Prof Bryan.
However, there is also a more serious form of the disease in which tumors progress beyond the bladder lining and into the muscles.
What causes bladder cancer?
Approximately half of bladder cancers are directly linked to ingestion of toxic chemicals known as aromatic amines and polycyclic aromatic hydrocarbons, which are abundant in industrial and manufacturing facilities and diesel exhaust. “If we go back to the history of bladder cancer, it has often been linked to people working in tire manufacturing and rubber manufacturing as well as synthetic dye manufacturing plants for decades,” says Prof Bryan.
However, the biggest contributor to bladder cancer is smoking, which is associated with 40 percent of transitional cell carcinomas. Cigarette smoke is rich in aromatic amines and polycyclic aromatic hydrocarbons, which are absorbed from the lungs and mixed into the bloodstream. The liver metabolizes these chemicals, which are then excreted into the bladder via the kidneys.
“They react with other components of urine and become reactivated, almost carcinogenic,” says Prof Bryan. “So your urine sits in your bladder for hours and contains potential carcinogens that can damage the DNA in the urothelial cells lining the bladder and initiate the process of transformation into malignancy. If you smoke 20 cigarettes a day and have been smoking for 10 years, your risk of developing bladder cancer is four times higher than someone who has never smoked.” .
Another important risk factor for bladder cancer is just being male. Men are three times more likely to have the disease than women, and Prof Bryan’s research group is trying to understand why this is and whether this could point to future treatment options.
“This is just speculation, but perhaps women have some kind of innate protection against bladder cancer,” says Prof Bryan. “It could be hormone related. Most likely it will ultimately have to do with how the immune system works, and immune surveillance of rogue bladder cells is better in women than in men. But these are just hypotheses.”
What are the symptoms?
Oncologists estimate that 60 percent to 80 percent of patients diagnosed with bladder cancer see their doctor after seeing blood in their urine, a symptom known as hematuria.
“This is a pretty important sign that should not be missed,” says Prof Hussain. “Not all haematuria may be bladder cancer, it can also be related to urinary tract infections, but it can be an early sign of cancer. People who see it should contact their GP and then be referred to urology services, where hospitals have a one-stop clinic that provides imaging scans for anyone presenting with haematuria.”
How is bladder cancer diagnosed?
For many years, bladder cancer has been diagnosed through flexible cystoscopy, a test in which a thin, fiber-optic tube is passed through the urethra and allows the doctor to look directly at the inside of the bladder.
However, this has a number of limitations, from patients’ discomfort to the number of trained professionals required to perform the examination. If NHS reviews confirm that the Galeas Bladder urine test is comparable to flexible cystoscopy, it could be rolled out nationally.
Simon Crabb, professor of experimental cancer treatments at the University of Southampton, says urine-based tests could be used as part of screening programs in the future if they prove accurate enough.
“We don’t currently have a screening test for bladder cancer,” says Prof Crabb. “A lot of advice about early detection is about people recognizing blood in their urine. Many patients have something completely benign, but currently this is the best way to detect it at an early stage. Bladder cancer and urine-based testing make sense and may be the way to go.” “
Any patient diagnosed with bladder cancer, even at an early stage, will need to get used to regular ongoing surveillance. “Management of patients treated for early bladder cancer will be based on monitoring with camera (cystoscopy) examination,” says Prof Bryan. “Some patients will experience this every three or six months for many years.”
How is it treated?
There are four different stages.
Patients with early-stage bladder cancer can often be effectively treated with a type of immunotherapy known as Bacillus Calmette Guérin (BCG), which is administered directly to the organ through a catheter. Prof 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 penetrated the muscle.
For the 20 to 25 percent of patients with muscle-invasive bladder, there are two main options: chemotherapy followed by surgery or chemoradiation. The latter is an alternative to surgical removal of the bladder and involves a combination of chemotherapy and radiotherapy treatment to sensitize the cancer cells to radiotherapy.
However, just under 1 in 10 patients are found to have advanced or metastatic bladder cancer, which has not only penetrated the bladder muscle but also spread to other organs beyond the bladder.
“Treatments here will unfortunately be incurable, only palliative,” says Prof Hussain. “But the treatment landscape in metastatic cancer has changed significantly and there is much more hope. There are a range of new drug options, and patients are living longer and doing well.”
Prof Hussain says the average survival rate for a patient with metastatic bladder cancer is between 12 and 18 months, but this has increased to between 24 and 30 months in the last few years, particularly with the emergence of a new class of drugs. Medicines called immune checkpoint inhibitors, administered through drops into the bloodstream. These drugs are now available as standard of care on the NHS.
More recently, clinical trials using immune checkpoint inhibitors in combination with another class of drugs called antibody-drug conjugates have shown promising results in improving survival outcomes of patients with metastatic bladder cancer.
“You can actually only give six cycles of chemotherapy over about three to four months, because then the patient’s bone marrow starts to crack,” says Prof Hussain. “But immune checkpoint inhibitors are very smart drugs that use 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 to the bladder in patients with early-stage cancer, testing whether this could treat the cancer more effectively. Prof Hussain is currently taking part in a trial examining a special immune checkpoint inhibitor called atezolizumab in patients with non-muscle-invasive cancer for which BCG has not worked, or in people with muscle-invasive cancer who are not well enough for treatment. chemotherapy.
“I think it’s important to highlight the hope that we see,” says Prof Hussain. “Patients are living longer and having a better quality of life, all thanks to these new drugs.”
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