The most common presenting symptom of bladder cancer is painless haematuria (blood in the urine). Blood in the urine may be visible to the naked eye (gross haematuria) or invisible to the naked eye but detected on a formal urine examination (microscopic haematuria).
It is very important to note that haematuria associated with bladder cancer may be intermittent. That is, days, weeks, or even months may pass after an episode of haematuria during which no blood is seen in the urine. It is therefore vitally important that any episode of gross haematuria is reported to your doctor even if it occurred days, weeks or even months ago.
Other symptoms sometimes associated with bladder cancer include:
- A change in bladder habit (unexplained urinary frequency or urgency)
- A recent history of difficulty passing urine
Bladder cancer rarely causes pain in until it has reached an advanced stage.
Diagnosis and Staging
Once the above symptoms have been reported, a series of tests are required to exclude the presence of bladder cancer.
These tests include:
- Urine culture and microscopy
- Urine cytology (to examine for the presence of cancer cells in the urine)
- Basic blood tests including a full blood count and kidney function studies
- Cystoscopy, this is an endoscopic examination of the bladder. If a bladder tumour is identified at the time of a cystoscopy then a transurethral resection of the bladder tumour (TURBT) is performed to make a formal diagnosis of bladder cancer and to help determine how deeply the cancer is growing into the wall of the bladder
- Imaging studies:
- CT IVP (this is a CAT scan in which intravenous contrast is administered in order to accurately assess the kidneys, the inner lining of the kidneys, the ureters and the bladder)
- Ultrasound of the urinary tract. In patients where intravenous contrast may cause severe kidney problems an ultrasound is sometimes used as a preliminary investigation and is combined with studies that are performed during a cystoscopy.
Staging and Grading of Bladder Cancer
|Carcinoma in situ||High grade cancer cells filling the inner lining of the bladder|
|Ta||Variable grade cancer cells occupying part of the inner lining|
|T1||Cancer cells have broken through the inner lining into lamina propria|
|T2||Cancer cells have invaded the muscle of the bladder|
|T3||Cancer has grown through the muscle into fat around the bladder|
|T4||Cancer has grown into surrounding organs (eg rectum)|
The treatment of bladder cancer depends on the stage of the disease (how deeply the cancer is growing into the bladder and whether it has spread beyond the bladder) and the grade of the cancer.
The stage of the disease is assessed by the results of the bladder biopsy or TURBT. The specimen is examined by a Pathologist who is able to accurately determine how deeply the tumour is growing into the wall of the bladder. To determine whether the cancer has spread beyond the bladder, the CT IVP is used. During analysis of the specimen by the Pathologist, the grade of the cancer is also determined. Higher grade cancers behave more aggressively and lower grade cancers are less likely to grow into the wall of the bladder or to spread beyond the bladder. Dr Sved works closely with expert Uropathologists at RPA, Strathfield Private and Bankstown Hospitals. In cases where there is a doubt as to the degree of invasion of a bladder tumour, multidisciplinary meetings are held to help determine the most appropriate managament strategy.
Treatment of Non Muscle Invasive Bladder Cancer (Stages Ta, T1 and CIS)
The treatment of non muscle invasive bladder cancer will combine some or all of the following factors
- Cystoscopy and TURBT
- Intravesical chemotherapy (Mitomycin C)
- Intravesical immuno therapy (intravesical BCG)
Cystoscopy, bladder biopsy +/- TURBT
Whilst a cystoscopy and bladder biopsy are always required to accurately stage bladder cancer, it may also be the only surgical treatment required for some bladder cancers. This is particularly the case for low grade, non invasive bladder cancers (eg some Ta cancers). Often this procedure needs to be repeated in order to continue to keep the bladder clear after the initial diagnosis is made.
If a stage T1 tumour is discovered on the initial biopsy, a repeat biopsy is important to ensure that deeper invasion of cancer cells into the muscle of the bladder has not been missed. There is a well-recognised risk of underestimation of depth of cancer invasion in T1 tumours. This is particularly true when certain pathological features are present. These include:
- Larger tumours
- Invasion deep into the lamina propria
- Associated areas of carcinoma in situ
- Invasion of blood vessels and lymphatic vessels
Intravesical Chemotherapy (Mitomycin C)
Following the diagnosis of a non muscle invasive bladder cancer, a single dose of chemotherapy is often instilled into the bladder within 24 hours of tumour resection. This is known to reduce the risk of tumour recurrence by approximately 40%. When multiple tumours are present, a single dose is inadequate and a full course (six to eight weekly installations) is required to reduce the risk of cancer recurrence. There is also evidence that maintenance doses monthly can further reduce the risk of tumour recurrence.
More detail is available for those who require intravesical Mitomycin C.
For higher grade, non muscle invasive bladder cancers (eg stages CIS and T1), intravesical chemotherapy may not be adequate treatment. In these cases, intravesical BCG is administered. This usually takes the form of six weekly instillations. After this course has been completed, a follow-up cystoscopy is performed to determine whether the cancer has been eradicated. A further six week course may be required. Sometimes prolonged course, consisting of three weekly installations every six months (maintenance BCG therapy) is used. There is evidence that if a patient can tolerate maintenance BCG, this may confer a reduced risk of cancer recurrence and progression to more aggressive disease. With maintenance BCG, 85% of patients with CIS will be disease free at 6 months.
Patients who respond to BCG but in whom side effects are disturbing, reduced doses (1/2 or 1/3) may be used.
If a high grade, non muscle invasive bladder cancer returns despite intravesical BCG therapy, more radical treatment may be recommended, consisting of removal of the entire bladder (radical cystectomy).
More detailed information is available for those who will receive intravesical BCG.
In some cases, intravesical therapies such as chemotherapy and BCG are not adequate treatment for high-grade, invasive bladder cancers (Stage T1). There is mounting evidence that early cystectomy may be the treatment of choice in some cases and that a trial of other, less aggressive treatment may allow time for cancer cells to invade deeper and possibly metastatsize. Situations where early cystectomy may be the treatment of choice for stage T1 disease include:
1. Multifocal T1 tumours
2. Invasion of cancer cells deep into the lamina propria layer
3. Associated Carcinoma in situ
4. Associated kidney blockage
5. The presence of residual invasive cancer cells after the initial biopsy
6. Young, otherwise healthy patients
Recent studies conducted at centres of excellence around the world have shown that the presence of residual invasive cancer (even if not muscle-invasive) is a predictor of future cancer progression. In one large study, 82% of patients with residual invasive cancer cells after initial biopsy progressed to life-threatening muscle-invasive cancer within 5 years. For this reason, many experts recommend bladder removal at the time of diagosis rathger than a trial of intravesical BCG for patients with aggressive T1 bladder cancers.
Treatment of Muscle Invasive Bladder Cancer
When bladder cancer invades into the deep muscle of the bladder wall or through the entire thickness of the bladder, it becomes a life threatening cancer. In this case, very aggressive treatment is required. The choice of treatment depends on a number of factors including the position of the cancer within the bladder, whether there are associated abnormal areas in the bladder, the age and general state of health of patient.
Aggressive treatment is also sometimes required for some tumours which are not invading the muscle of the bladder but have a higher likelihood to do so regardless of treatment (see above). Examples of these situations include:
- High grade tumours (T1 and CIS) which have not responded to BCG
- Large T1 tumours which cannot be fully resected by TURBT
- Certain subtypes of T1 tumours (eg micropapillary pattern)
In broad terms, the treatment options for muscle invasive bladder cancer consist of:
- Partial cystectomy
- Radical cystectomy and urinary diversion
- Radical radiation therapy (+/- systemic chemotherapy)
- Palliative radiation therapy
In approximately 5% of cases of muscle invasive bladder cancer, the tumour is localised to one, small, accessible portion of the bladder, usually at the dome of the bladder. In this case, it may be possible to remove only the cancerous portion of the bladder, leaving the remainder of the bladder intact. Patients who undergo a partial cystectomy require lifelong surveillance consisting of periodic cystoscopies and imaging studies to monitor for any sign of cancer recurrence.
In most cases of muscle invasive bladder cancer, the treatment of choice is removal of the entire bladder. In the male patient, this involves removal of the bladder and prostate gland together with draining lymph nodes. In the female patient, the operation consists of removal of the bladder, a portion of the front wall of the vagina, the uterus and ovaries, together with draining lymph nodes.
Following removal of the urinary bladder, the urinary stream must be diverted. There are two main ways in which this can be achieved:
- Ileal conduit urinary diversion. This is the most common form of urinary diversion. A short segment of small bowel is isolated and one end of the small bowel is brought out to the skin, usually on the right side. The ureters, which drain urine from each kidney are then joined onto this small segment of bowel and the urine is collected by means of an external collection device adherent to the skin.
- Ileal neobladder formation. This is a more complicated procedure and not every patient is suitable for this type of urinary diversion. In this procedure, a segment of small bowel is isolated and fashioned into a spherical shape. One end of the spherical pouch is joined to the urethra and the ureters are joined onto another portion of the spherical pouch. Therefore, there is no external drainage of urine and the body appearance is normal.
Detailed information is available for those who require radical cystectomy.
In selected cases, where patients are either not fit for a radical cystectomy or when the cancer cannot be removed by radical cystectomy, radiation therapy possibly in conjunction with chemotherapy may provide good control of the cancer. Indeed, radiation treatment alone may cure some muscle invasive bladder cancers in selected patients but is usually reserved for palliative treatment of bladder cancer in patients who are not fit for surgery.
Metastatic Bladder Cancer
When bladder cancer has spread beyond the bladder to other sites within the body, it is no longer curable. In this case, platinum based chemotherapy is the standard treatment. This is be administered after assessment by a medical oncologist. Dr Sved works closely with a number of medical oncologists who specialise in chemotherapy for bladder cancer at RPA, Strathfield Private Hospital, Bankstown Hospital and The Sydney Cancer Centre.