Bladder cancer, the most common form of which is transitional cell carcinoma (TCC) or urothelial carcinoma, is a cancer of the inner lining of the bladder. It is responsible for approximately 3% of all malignancies diagnosed in Australia each year. At an early stage of growth it may not produce any noticeable signs or symptoms, but may cause microscopic blood on a routine urine test. Common symptoms of bladder cancer include blood visible in the urine (haematuria) which is usually painless and appears intermittently, a burning sensation during urination, and urinary frequency/urgency. It is important to note that these symptoms are similar to those of a urinary tract infection, and therefore should be further investigated if such an ‘infection’ does not resolve with antibiotics.
Risk factors for bladder cancer
- Smoking – commonest risk factor, chemicals inhaled are excreted by the kidneys and expose the lining of the urinary tract to an increased cancer risk
- Occupational exposure to certain chemicals (e.g. chemical dyes in the textile or rubber industry, coal tar pitch) ·
- Drugs – old fashioned headache tablets (phenacetin), certain chemotherapy agents (e.g. cyclophosphamide) ·
- Radiotherapy to the pelvis
- Longstanding inflammation within the bladder e.g. from a long-term catheter
- Other rare conditions e.g. schistosomiasis (disease endemic in parts of Africa and the Middle East which can infect the urinary tract)
Types of bladder cancer
This is cancer that is confined to the lining of the bladder and has not invaded into the underlying muscular bladder wall. About 75% of newly diagnosed bladder cancers are superficial. These cancers can be dealt with, at least initially, by local treatments (see below). There are 3 broad categories of superficial bladder cancers:
These cancers project into the cavity of the bladder, like coral growing on a reef (see figure 1). They vary in size and while they can grow very large, the risk of them turning into invasive cancers is only around 5%. These tumours are shaved off under a general anaesthetic by passing a camera through the urethra and into the bladder – transurethral resection of bladder tumour (TURBT – see below). Unfortunately however they have a tendency to recur after removal in around 50-70% of patients, and occasionally can be difficult to control. For patients with frequent recurrences, large tumours, or adjacent areas of carcinoma in situ (CIS), further treatment by flushing of drugs into the bladder is required (see below).
These cancers have begun to invade into the deeper layers of the bladder wall lining (but not muscle), and pose a significant risk of invading further and spreading elsewhere in the body. Around 30-50% of superficially invasive tumours will progress to muscle-invasive tumours (see below) and following TURBT, require treatment with intravesical therapy (with flushing of chemotherapy or immunotherapy drugs into the bladder) following surgery. If this is unsuccessful then more radical treatments may need to be considered depending on the individual circumstance.
Carcinoma in situ (CIS)
This is transformation of the lining of the bladder into flat areas of cancer cells that have not formed a growth or begun to invade through the bladder wall. It appears as flat, red, inflamed areas within the bladder, or may not be visible with the naked eye. CIS cannot be surgically removed, since it may affect large areas and it is not possible to see where it stops and starts. It carries around a 50% risk of developing into an invasive cancer, and therefore requires treatment with intravesical therapy (with flushing of drugs into the bladder).
Muscle-invasive bladder cancer
This is a life-threatening cancer that has invaded into the muscle of the bladder and is at risk of growing into nearby structures or spreading to lymph nodes and other distant organs (e.g. lung, bone, liver) via the bloodstream. Patients with muscle-invasive cancers may require a number of tests to assess whether the cancer is anywhere else within the body such as a chest X-ray, bone scan and CT scan. To surgically remove these tumours requires removal of the entire bladder, called a radical cystectomy (see below). An alternative option is a combination of radiotherapy and chemotherapy.
Figure 1. Appearance of superficial bladder cancer (TCC) at cystoscopy
Trans-Urethral Resection of the Bladder Tumour (TURBT)
This is the initial step for treatment of all bladder cancers. Performed under general or spinal anaesthesia, removal of the tumour is carried out using a slightly larger version of a cystoscope, called a resectoscope, passed through the urethra. The cancer is removed by shaving away the tumour until it is resected flush with the bladder wall. Biopsies of the tumour bed are performed to assess for any deeper invasive cancer cells, and samples may be taken elsewhere in the bladder, to look for areas of CIS.
The shavings of tumour are washed out of the bladder for analysis under the microscope and any bleeding is controlled with cautery. TURBT enables both removal of the tumour and an accurate diagnosis. For superficial tumours, this may be all that is required.
There is now evidence that flushing the bladder with a single dose of chemotherapy (e.g. Mitomycin) via a catheter immediately after TURBT kills any freely floating cancer cells that could potentially implant back into the bladder and cause a new tumour to grow. This is not absorbed into the bloodstream, so there is no systemic toxicity, and there is very little risk of any significant side effects.
Intravesical treatment is flushing the bladder with a drug to kill any remaining cancer cells and prevent recurrence of treated bladder tumours. It is only suitable for superficial bladder cancers. Intravesical treatments are given by inserting a urethral catheter (small tube via the urethra into the bladder), and flushing around 50ml of dissolved medication into the bladder. The catheter is clamped for 1-2 hours, following which it is unclamped to empty the bladder, then removed. This treatment is a course performed weekly as a day procedure in hospital usually for 6 weeks. A cystoscopy is repeated around 6-8 weeks later to reassess the bladder and see how successful the treatment has been. There are two main types of intravesical treatments:
BCG (Bacille Calmette-Guerin)
This is a form of immunotherapy, or stimulation of the body’s own immune system to kill cancer cells. BCG is a sample of inactivated bacteria (the same as the vaccination for tuberculosis, or TB) that increases the immune response against foreign cells, including cancer cells. Minor side effects are common and include irritation of the bladder causing frequency, urgency, and bladder discomfort. These symptoms usually subside once the treatment is finished. A small number of people may experience flu-like symptoms during treatment, and around a third experience intermittent blood in the urine. A rare side effect is a systemic infection by the bacteria, and for this reason anyone who has a pre-existing immune deficiency is not suitable for BCG treatment. Intravesical BCG is the best first line treatment for CIS, with a successful response in 75%. It is also the most effective intravesical treatment in preventing or delaying recurrence of superficial bladder cancer.
Given the same way as BCG, chemotherapy can be used to reduce the recurrence of superficial bladder cancer, although is less effective. An advantage is a lower incidence of irritative bladder side effects, although it is usually used in those patients who are not suitable for BCG treatment. Examples of drugs used include Mitomycin, Adriamycin, and a newer agent, Gemcitabine.
Follow-up of superficial bladder cancer
Once the cancer has been removed and further treatment administered as appropriate, a repeat cystoscopy is carried out at around 3 months to reassess the bladder for recurrence of the original tumour, or regrowth of new tumours. If this is all clear, then regular ‘check’ cystoscopies will be carried out, usually using a flexible cystoscope. This is a very minor procedure, taking just a minute or two, and can be performed under sedation or local anaesthetic only.
Radical cystectomy – removal of the bladder
Removal of the bladder (in men including the prostate, and in women including the uterus and a small part of the vagina) is the gold standard treatment for muscle-invasive bladder cancers, or those superficial bladder cancers that have not responded to TURBT and intravesical treatments. This is major surgery, taking between 3 and 6 hours, and requiring recuperation in hospital for 1-2 weeks. Once the bladder has been removed, another way must be found for the body to drain urine. The operation therefore involves reconstruction of the urinary tract using a length of disconnected small bowel to carry the urine from the ureters to either the skin (via a ‘stoma’) or back through the urethra. There are three methods of reconstruction: ·
This is the most common form of reconstruction and involves disconnecting 15-20cm of small bowel (ileum), and attaching the 2 ureters to one end of it. The other end is then brought through the abdominal wall as a ‘stoma’ or opening, which drains urine into a bag that is stuck onto the skin. The bag needs to be emptied intermittently as it fills with urine. The advantages of this approach is that it is technically easier to perform, with slightly less risk of complications than the other methods of reconstruction, and the stoma is relatively easy to manage. The major disadvantage is coming to terms with a stoma and bag.
This means ‘new bladder’, and involves creating an internal pouch out of disconnected small bowel to act as a bladder. The ureters are joined to it and the pouch is then connected to the urethra. The advantage is that there is no stoma, with urine expelled more naturally through the urethra. Disadvantages include a longer operation with slightly greater risk of post-operative complications, including incontinence, or the neobladder not emptying properly and requiring regular passage of a catheter to drain urine.
Dry stoma, or ‘continent diversion’
This is the creation of an internal pouch out of bowel which is connected to the skin to form a stoma, like the ileal conduit, except with a smaller opening. However rather than requiring a bag to catch the urine, this stoma has a valve that prevents urine from leaking out. The urine therefore collects in the pouch, which is drained by passing a small tube through the stoma a few times per day. Advantages of this approach include a smaller stoma with no bag required. Disadvantages include a slightly longer operation, and around a 5-10% risk of problems with the stoma – either difficulty passing the tube, or failure of the valve to completely prevent leakage of urine.
In patients with bulky muscle-invasive bladder cancer, a course of chemotherapy may be recommended before or after surgery, to increase survival.
Radiotherapy and Chemotherapy
This treatment is administered by a radiation oncologist and medical oncologist, both with urological expertise, acting as part of a team in conjunction with the urologist.
Who gets Radiation Therapy?
Most studies have demonstrated surgery to be a more effective treatment than radiotherapy for invasive bladder cancer. Over recent years however, techniques of delivering radiotherapy have improved, and the use of chemotherapy in combination has also increased the chances of cure. Therefore selected patients with small, solitary tumours and no obstruction to the ureters may have cure rates approaching those of surgery with radiotherapy. Other patients suited better to radiotherapy are those in poor general health unfit for major surgery, those with large and locally advanced tumours in whom surgery is not possible, and those with cancer that has spread throughout the body in whom radiotherapy is used to control local symptoms for palliation.