Bladder cancer information leaflet
Causes of bladder cancer
In the western world, bladder cancer is commonly a growth of the lining of the urinary system [transitional cell cancers or TCCs] and is predominantly environmental, being caused by cancer promoting chemicals [carcinogens] excreted in the urine. It is commoner in men than women [3:1]. In some parts of the world, it follows infestation with bilharzia [schistosomiasis].
Classically, there are occupations which have an acknowledged risk of bladder cancer—those in the rubber industry or those handling aniline dyes. Specific chemicals are highly carcinogenic for the bladder [2-naphthylamine, nitrosamines etc], and these have been identified in cigarette smoke.
Sadly, the evidence supports the contention that many bladder cancers are cigarette smoking related and hence self induced. There are many other environmental carcinogens that we breathe in on a daily basis which may predispose to the development of bladder cancer.
The bladder is a storage organ, hence the reason why most of these cancers occur in the bladder where the chemicals are in contact with the lining for longest. The upper part of the urinary tract [kidneys and ureters] are places of rapid urine transit and, as a result, cancers in these are comparatively rare.
A different type of bladder cancer [squamous cancers] may also occur in older women with chronic urinary tract infection.
Presentation
Blood stained urine [heamaturia] is the cardinal sign of bladder cancer. It is classically painless and commonly intermittent. All patients with blood stained urine [excepting young women with a proven urinary tract infection] should be referred for investigation.
Blood stained urine has a risk of 20-25% of cancer [bladder, renal and prostatic] and where blood is found on testing only [microscopic haematuria] there is a risk of around 2-4%. Occasionally, bladder cancer presents with infection, or is found incidentally on scanning.
Investigation of a patient with suspected bladder cancer
Process
Under the “Improving Outcomes Guidance for Urological Cancers” [NICE , National Institute for Clinical Excellence, 2003], all patients with blood stained urine are suspected of having bladder cancer and, in the UK, must be seen by “a specialist” within 2 weeks. All bladder cancer should now be managed by Urologists who are part of a Cancer Network Associated Multidisciplinary Team [MDT]
Initial investigations
Most patients are now seen in specialist clinics and will have a telescopic bladder examination [cystoscopy] under local anaesthetic as the initial investigation.
Specimens of urine will also be taken for culture [for infection] and cytology [cancer smear] and xrays or scanning of the urinary tract arranged.
Xrays and ultrasound
There remains some debate about the ideal way of scanning for patients with blood stained urine and suspected bladder cancer. Traditionally x-raying the kidneys and bladder [IVP Intravenous pyelogram or IVU Intravenous Urogram] is the standard but it must be complemented with ultrasound, to exclude kidney cancer. Ultrasound alone is probably adequate in most cases.
CT or MRI scans are reserved for staging muscle invasive bladder cancer.
Definitive diagnosis
The definitive diagnosis is made on biopsy, commonly taken under anaesthesia. It is necessary to include bladder muscle in the biopsy to exclude or confirm muscle invasion, the single most important prognostic feature of bladder cancer.
Histological types and grading
Cancers of the bladder are described by pathologists in three grades, representing their overall level of malignancy or “cancerousness”. These are called well differentiated [G1], moderately differentiated [G2] or poorly differentiated [G3]. These grades have predictive value and have different treatments.
Staging
Staging is the process of “mapping out” the tumour and takes into account the findings at bladder examination, what the tumour feels like when you are asleep, the biopsy and the results of the scans. It is clearly essential for staging to be as accurate as possible for the correct treatment to be recommended.
Superficial bladder cancer, treatment strategies and options
The overall intention of treatment in superficial bladder cancer is bladder preservation and the achievement of a normal life expectancy, by detecting progression of the tumour and preventing recurrence. This should be achieved in the majority of cases by a combination of treatment and surveillance [check or review cystoscopies]
Newly diagnosed superficial bladder cancer is resected under general anaesthetic, an operation called TURBT [Trans Urethral Resection of Bladder Tumour].
After this, a single instillation of an anticancer drug [Mitomycin C] is given through the post operative catheter within 6-24 hrs of resection. In superficial bladder cancer, the instillation of Mitomycin C within a few hours of resection significantly reduces the incidence of recurrent disease at 3 months.
Treatment options for superficial bladder cancer [pTa]
Cystoscopy and diathermy
Surveillance bladder examinations [cystoscopy or “check” cystoscopy] are the backbone of the management of superficial bladder cancer. Many small recurrences are cauterised with diathermy [literally burnt off], or biopsied to detect change.
Chemotherapy drugs put into the bladder
The anticancer drug Mitomycin C placed in the bladder after the first treatment is now standard treatment for any new bladder tumour. It may also be used as a specific treatment for rapidly recurring superficial bladder cancer. It is then given in a series of 6 weekly instillations through a catheter tube. It is probably best used in better differentiated tumours and has a good chance of inducing a remission for a time.
Intravesical immunotherapy [BCG]
The use of intravesical [given into the bladder] BCG as a non specific immune stimulant is now standard practice in high risk superficial bladder cancer. It is again given in a course of six weekly instillations.
BCG has been the subject of extensive studies and there is no doubt that it is a very effective treatment for high grade [poorly differentiated] superficial bladder cancer or carcinoma in situ [CIS]. There remains debate about its ability to prevent tumour progression, although evidence is accruing that it may do.
Patients treated with BCG remain under a life time threat of recurrence of their disease and progression to muscle invasive bladder cancer. Perhaps 50% of patients with an apparent satisfactory response may eventually develop invasive and, hence, life threatening cancer.
Occasional severe reactions are seen with BCG use, either as a short term cystitis like illness, which might need treatment with the drug Isoniazid, or a more chronic long term syndrome of frequency and pain on passing urine. The risk of these reactions is low.
Once the bladder tumour has been treated and follow-up biopsies are shown to be negative, a maintenance programme of 3 weekly instillations of BCG into the bladder may be given every 6 months for three years [Maintenance BCG programme].
Compliance with this regime is poor, with a high drop out rate due to side effects. There is still debate as to whether BCG prevents progression of CIS to invasive bladder cancer.
Treatment strategies for early invasive bladder cancer [pT1]
It must be recognised that pT1 disease is already demonstrating invasive potential and has a significant risk of progression. The overall intention of treatment is bladder preservation and the achievement of a normal life expectancy.
Superficial bladder cancer [staged as pT1 by the pathologist] is already demonstrating a tendency to invade and hence is associated with a higher risk of progression and a poorer prognosis.
This tendency increases with the higher grades. Hence a poorly differentiated [G3] pT1 bladder tumour has a significant risk of progressing to a muscle invasive and hence life threatening cancer. This risk is increased if there is associated CIS [carcinoma in situ].
Better differentiated pT1 tumours are managed by resection [TURBT] and surveillance [check cystoscopy]. If any high risk factors are present [widespread invasion of the lamina propria, multifocality, size and rapidity of recurrence] then intravesical [given into the bladder] chemotherapy [MitomycinC] or immunotherapy [BCG] are given.
Poorly differentiated tumours [pT1G3] are always subject to repeat biopsy to confirm the stage. If confirmed, then intravesical immunotherapy is indicated [6 instillations of BCG]. If muscle invasion is detected, then the protocol for muscle invasive tumours is followed.
Widespread poorly differentiated pT1 tumour associated with carcinoma in situ [CIS] is a dangerous situation and serious consideration should be given to early radical cystectomy.
Treatment strategies for Carcinoma in situ [CIS]
Although classified as superficial bladder cancer, CIS is a completely different type of disorder and one which carries a high risk of progression to muscle invasive and hence life threatening bladder cancer. The prime intention of treatment is to eradicate the changes by immunotherapy, maintain surveillance and predict and prevent progression by cystectomy.
There appears to be two types of CIS. Firstly, there is CIS found in association with superficial tumours and is patchy. This may resolve with the resection of the papillary tumour, and seems to respond better to intravesical BCG [immunotherapy].
Secondly, there is widespread [primary] CIS which is often highly symptomatic, with frequency, dysuria and penile pain. It is always associated with strongly positive urinary cytology. It may be called “malignant cystitis” because of the symptoms.
BCG is given traditionally in six weekly instillations followed by a check cystoscopy and biopsy at 3 months. Persistent changes would give cause for concern. If the changes have resolved, then an attempt at maintenance therapy should be made with 3 instillations given at weekly intervals every six months for three years. Compliance with this regime is poor, with a high drop out rate due to side effects. There is still debate as to whether BCG prevents progression of CIS to invasive bladder cancer.
Widespread primary CIS is very dangerous and serious consideration should be given to early radical cystectomy, instead of attempting to conserve the bladder by the use of BCG.
Muscle invasive bladder cancer, treatment strategies and options
Muscle invasive bladder cancer is a serious disease and requires meticulous staging and treatment planning. In patients with a reasonable life expectancy, and localised disease, the intention of treatment is cure, but in the elderly, palliation may be a preferable strategy.
The presence of lymph node metastases [nodal secondaries] on x-ray or after node dissection at cystectomy, is a poor prognostic sign with a highly significant impact on survival. The presence of soft tissue or bony metastases makes the disease incurable.
Currently, cure can only be achieved by surgical excision [cystoprostatectomy in men, anterior pelvic clearance in women] or external beam radiotherapy.
Some patients receiving neo adjuvant chemotherapy [chemotherapy given before radical surgery] may apparently be cured, but at the present time, this is not a main stream primary strategy at present.
Once a bladder tumour has started to invade the detrusor muscle [bladder wall muscle], the chances of dying increase with the depth of invasion and grade of the tumour. A bladder cancer staged pT2a G1, G2 [invasion into the superficial layers of the bladder muscle but well to moderately differentiated] still has a reasonable prognosis, but a deeply invasive [pT2b] and poorly differentiated bladder cancer [G3] has a very poor prognosis, with a cure rate of less than 30-40%.
Cure of these cancers usually requires radical therapy, either radiotherapy or radical surgery.
At one time radiotherapy [with or without chemotherapy] was the mainstay of treatment in the UK and surgery was reserved for failures [salvage cystectomy]. Currently, however, primary surgery is the treatment of choice if the patient is fit.
In men, surgery comprises cystoprostatectomy [removal of the bladder and prostate with the lymph nodes], but in women it requires an anterior pelvic clearance, with a hysterectomy, removal of the ovaries and tubes and the upper third of the vagina. The risk of death from these procedures should be below 2%, with the surgery only carried out in centres where a large amount of this type of surgery is being routinely performed.
The role of neo adjuvant chemotherapy [chemotherapy given before radical treatment] remains uncertain, [a possible 5%, 5 year survival advantage] but there is no doubt that downstaging achieved with neo adjuvant chemotherapy seems to leads to a better outcome. The benefit of adjuvant chemotherapy [chemotherapy given after radical surgery or radiotherapy] is uncertain.
Clearly if the bladder is removed, then there is a problem. The urine must be “diverted” either into a stoma [a bag on the side] known as an ileal conduit or by bladder reconstruction [neo-bladder].
Urinary diversion after bladder removal [cystectomy]
Before 1950, the urinary flow was diverted into the colon [uretero-sigmoidoscopy]. This resulted in the passage of 4-5 wet stools per day. When done in young people it was surprisingly well tolerated and many coped well with the rectal frequency for many years. The re-absorption of chloride from the colon carried the life time risk of severe metabolic acidosis, and the presence of urine in the faecal flow increased the risk of colon cancer.
Merely bringing the ureters up to the skin as a diversion was largely unsuccessful because of narrowing at the skin opening and the difficulty in designing rubber bags that fitted well.
In the early 1950’s , Bricker introduced the concept of interposing a section of small bowel between the ureters and the skin as a conduit [the ileal conduit]. This allowed the construction of a larger stoma over which a bag could easily be fitted. The ileal conduit has remained the mainstay of urinary diversion after bladder removal ever since.
Bladder reconstruction [neo-bladder]
Efforts to create a replacement bladder started with the design of ectopic [ectopic means "not in the same place" , usually on the right side of the abdomen] reservoirs that required intermittent catheterisation through a continent stoma [one that allowed no urine to escape from the reservoir but allowed the passage of a draining catheter into it.] These designs have been modified many times over the years and have largely given way to the creation of orthotopic reservoirs [orthotopic means “in the same place”] that are attached to the native urethra, thus allowing urine to be expressed in the normal way.
Reading Urology Partnership is very experienced in bladder reconstruction and offers it to all suitable patients requiring bladder removal.
Treatment strategies for palliative care in bladder cancer
If death is inevitable from bladder cancer, then priority must be given to preventing death from locally recurrent disease and the associated misery of bleeding and strangury.
A team approach, with urologist, clinical oncologist, palliative care physician, clinical nurse specialists and the pain control team provides a multidisciplinary approach to palliation. This requires use of good symptom relief with pain control, palliative radiotherapy or chemotherapy, all of which aims at improving the quality of life and reducing pain and bleeding.
Urinary diversion or even cystectomy are justified as palliative measures for bleeding, pain and fistulation.
Author: Derek Fawcett, Consultant Urological Surgeon, Reading Urology Partnership
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