by Dr. Clarence Lei Chang Moh and Datuk Prof. Dr. Tan Hui Meng
The urinary bladder is a reservoir which stores and discharges urine at the appropriate time. Urine itself is produced from the 2 kidneys. Urothelial cancer may occur anywhere along the urinary tract, from the kidney to the proximal part of the prostatic lining. The most common site for urothelial cancer is in the bladder.
Symptoms
The most common symptom is that of blood in the urine. Other conditions such as urinary stones and infection can also give rise to blood in the urine, but these conditions are usually associated with some amount of pain or discomfort at urination.
Therefore, if one passes blood in the urine without any pain (a condition known as painless haematuria), one must rule out cancer of the urinary tract.
In the early stages, there are no other symptoms nor signs. Of course, the bleeding can be diluted by taking more fluids or diuretics. Haematuria detected during microscopic analysis also has similar implications and warrants a full medical evaluation. The bleeding from the tumour can be intermittent. Therefore, one must be ever vigilant, even if there is only one episode of painless haematuria.
Causes
Bladder cancer is commoner in the older age group (above 60 years of age) and is very rare in children. It is more common in males compared to females, with a ratio of 4 to 1. It is the 6th most common cancer in the US.
According to the National Cancer Registry of Malaysia 2002, it ranks as the 10th commonest cancer in males. For Malaysian men, it comprises 4.1% of all new cancers, with a peak incidence of 33.5 per 100,000 for men in the age group of 60 to 69 years of age.
Other than the above epidemiological factors, the most well known cause is smoking. Smoking increases the incidence of bladder cancer by 3-fold, and also worsens the outcome of bladder cancer patients who continue to smoke.
Certain chemicals (eg aromatic amines) used in industry (eg dye in textile or rubber) and in agriculture may increase the incidence of bladder cancer. Hence, workers in the rubber, chemical, leather, textile, metal, and printing industries are exposed to substances such as aniline dye and aromatic amines that may increase their risk for bladder cancer. However, such occupational hazards take up to 20 years to manifest.
Chronic infections and irritation (eg by kidney stones) may predispose to certain types of bladder cancers, eg squamous cell carcinoma (SCC).
Diagnosis
If you have blood in the urine, you should consult a doctor who specialises in the urinary tract, namely, a urologist. Based on the clinical features, he will be able to determine the relevance of your symptoms and decide on further tests.
Blood in the urine can be confirmed by a simple urine dipstix test. The red blood cells can also be quantified with microscopy.
The urologist will usually arrange for appropriate imaging studies of the urinary tract. A minimum screening test is that of an ultrasound of the urinary tract. A full urinary bladder would give a better image on ultrasound.
Nowadays, multi-slice computerised tomography (MSCT) give good pictures not only of the urinary tract but also any extension of the growth to any other areas, eg outside the bladder or the lymph nodes.
Intravenous urography, which can pick up a space-occupying growth along the urinary tract, can be done if the patient has a normal kidney function. The excretion of the radiocontrast material will indicate the functioning of the kidneys as well as the blood supply to the kidneys.
Initial Treatment
All suspected bladder tumours require endoscopic assessment which can be easily carried out by a urologist. A special endoscope called a cystoscope is used to examine the urinary bladder. Any tumour seen is then biopsied with a forceps, together with any other suspicious areas of the bladder.
Most bladder tumours are cancerous and biopsy alone (which may cause bleeding or tumour seedling) is insufficient. Endoscopic treatment is carried out, immediately after the biopsies, with another endoscopic instrument known as a resectoscope.
All the tumours that protrude into the bladder are resected. The base of the tumour is also resected as deep as possible, without making any perforation of the urinary bladder.
The bladder tumours are then sent separately for histological examination and staging. A dose of chemotherapy (usually Mitomycin-C) is then instilled into the bladder immediately to reduce the risk of tumour cells seedling to other parts of the urothelium.
Staging of Urinary Bladder Cancer
The staging system used is usually TNM staging (Tumour, Node, Metastasis). The T stage is divided into T1, T2, T3, T4 with T1 tumour being confined to the mucosa and T4 tumour invading the surrounding organs, eg the prostate.
About 70% of bladder tumours are confined to the mucosa at presentation. Many patients in Malaysia tend to procrastinate and eventually have treatment only when the tumours have already invaded the bladder muscle layers.
Another important feature of bladder cancer is that of the grade of cells of the cancer, with grading (1) indicating well differentiated cells, grade (2) moderately differentiated and grade (3) poorly differentiated.
Bladder cancers in the higher T stage, with nodal involvement, metastasis and poorly differentiated bladder cancers are more aggressive and more likely to spread to adjacent or other parts of the body.
Definitive Treatment
After the initial endoscopic treatment by the urologist, definitive treatment is then stratified according to its stage and grade.
For patients whose cancer is localised to the mucosa, the treatment remains that of endoscopy. A second cystoscopy with a view to further biopsies and endoscopic resection is undertaken at around 6 weeks. This is to ensure that the previous endoscopic treatment is adequate and there is no understaging of the bladder cancer.
Thereafter, the patient can be followed up with 3-monthly cystoscopy for 2 years, 6 monthly cystoscopy for another 2 years and then yearly cystoscopies. In the event the patient has recurrent gross haematuria or if there is progression of the cancer earlier, a change of treatment is necessary.
For such superficial bladder tumours who tend to recur, a more intensive chemotherapy into the bladder is necessary to control the cancer. This may be in the form of chemotherapy (eg Mitomycin-C, MMC) or immunotherapy with BCG (Bacillus Calmette-Guerin).
MMC or BCG ± Interferon are usually given into the bladder on a weekly basis for 6 weeks. BCG has been used in the prevention of tuberculosis (TB) for a long time. When BCG is given into the bladder, it induces a very strong reaction in the body's immune system to kill the bladder cancer cells.
Cancer Invade Deep Into the Bladder Muscle
Such cancers are not amendable to endoscopic resection as this would create a hole in the bladder. If the patient is fit and there is no evidence of spread to the lymph nodes or metastasis (eg to the liver, lung or bone), the standard treatment is to remove the entire urinary bladder. This is known as radical cystectomy.
A new urinary bladder has to be constructed from the segments of isolated intestines. A simple one is that of the ileal conduit. In the ileal conduit, one end of the intestines is joined to both urinary tubes (ureters) draining the kidney, and the other end comes up to the abdomen as a stoma.
For suitable patients, the new constructed bladder may be reconnected to the urethra and the patient may be able to empty his or her urine normally or taught to empty with a clean catheter.
If the patient is not fit for radical long surgery, another option is external radiotherapy.
Tumour Spread Beyond the Bladder
If the patient is reasonably fit, then intravenous chemotherapy has been shown to be of some benefit. However, the benefits of chemotherapy have to be weighed against that of its side-effects.
For bladder cancers which are limited to the mucosa, the prognosis is good. However, these patients do require close monitoring.
For cancers which have spread outside the bladder and require radical cystectomy or radiotherapy, the prognosis is moderate. The mean 5-year survival of such bladder cancers is about 85%.
For patients who have bladder cancers extending to the lymph nodes or metastasis to other organs, the prognosis is poor. Such patients should go for good palliative treatment. If the patient continues to smoke, the outcome or prognosis is worsened.
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