BLADDER CANCER
Urothelial cancer is common. The majority are transitional cell carcinomas that arise from the
specialised waterproof epithelium that lines the urinary tract. In men, this extends from the
tips of the renal papillae to the navicular fossa; in women, to halfway along the urethra.
Tumours can arise at any site in this epithelium and are often multifocal. The bladder is the
most common site.
Seventy percent of urothelial tumours are superficial at presentation; two-thirds will
subsequently recur locally or elsewhere in urinary tract, and in 10-15%, the recurrence will be
invasive. This potential instability of the urothelium is often described in terms of a "field
change".
Urothelial cancer:
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is uncommon before 50 years of age
is most frequent in incidence at 65 years of age
is more common in males by a factor of 3:1
in adults aged 15+ years in England and Wales in 1992 - there were 12,008 cases and
the number per annum per 2000 population was 0.47 (1)
95% affect the bladder; 5% affect the upper tracts
in 90% of cases, presentation is with macroscopic haematuria (1)
5-10% of patients present with microscopic haematuria
is four times as common as renal adenocarcinoma
has a 20 times more common incidence in paraplegics
is common in industrialised countries
is uncommon in the developing world except in bilharzial areas
Note that both microscopic and macroscopic haematuria, when caused by a urothelial cancer
are intermittent. Therefore repeat urine testing can be negative for haematuria in the
presence of a tumour (1).
Aetiology:
No single causative factor is identifiable in the majority of cases. In others, there may be an
association with:
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cigarette smoking - by itself, is associated with a 2-fold increased risk. Thought to be
due to urinary excretion of inhaled carcinogens. Smoking may act synergistically with
other risk factors.
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occupational exposure to carcinogens widely used in the rubber, cable, textile and
printing industries. For example,beta naphthylamine, benzidine, 4-diphenylalinine, and
auramine and magenta dyes. Such exposure can be proven in only a small proportion
of patients. There may be a latent period of 15-20 years. The bladder is particularly
vulnerable as it exposed to urine for longer than other parts of the urinary tract.
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drugs - e.g. phenacetin, aspirin, cyclophosphamide.
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fungal toxins in Balkan nephropathy
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endogenous carcinogens - e.g. nitrosamines, tryptophane metabolites (aminophenols)
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squamous cell carcinoma is associated with chronic irritation and squamous metaplasia
due to bladder stones or schistosomiasis. The latter is the main cause of bladder
cancer worldwide.
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adenocarcinoma may develop in peristent urachal remnants
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adenocarcinoma or squamous carcinoma may be associated with bladder exstrophy
Pathology:
Classification:
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transitional cell carcinoma - 90%
squamous carcinoma - 5-8%
adenocarcinoma - 1-2%
sarcoma - rare
Distribution:
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calyces and renal pelvis - 9%
ureter - 1%
bladder - 90%:
o posterior and lateral walls - 70%
o trigone and bladder neck - 20%
o vault - 10%
o diverticulum - 1-5%
urethra - less than 1%
Carcinoma in situ is a potentially aggressive tumour that may occur anywhere in the urinary
tract. Malignant change is confined to the bladder mucosa.
Tumours in the upper urinary tract often present late.
Spread:
The spread of urothelial cancer is via the following routes:
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direct invasion - through the bladder wall and perivesical fat, and into adjacent
structures such as the prostate and uterus
lymphatics - there are few lymphatics immediately under the bladder mucosa but they
are abundant in its muscle wall. Bladder cancer that penetrates the muscle quickly
reaches pelvic lymph nodes.
haematogenous distant spread - to liver, lungs, bone, and brain
Features:
Features of the primary urothelial tumour may include:
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painless total haematuria - the classic presentation of bladder cancer, occurring in 7090% of cases; 20% of patients with haematuria are found later to have a urinary tract
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tumour. In 10% of patients over 45 years with microscopic haematuria, tumour is
responsible.
ureteric colic - may occur due to clots from an upper tract lesion. Long, stringy clots
may be seen in the urine. Heavy bleeding may cause obstruction.
sterile pyuria, i.e. pus cells without urinary infection. May also occur with calculi,
tuberculosis, partially treated infection.
malignant cystitis - frequency, dysuria and urgency. A common presentation of
carcinoma in situ. Haematuria may be absent.
urinary tract infection in a man, or recurrent UTI in a woman
palpable suprapubic mass
Secondary features may include:
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bladder outflow obstruction - involvement of bladder neck
ureteric obstruction - involvement of ureteric orifices. Causes renal pain and
hydronephrosis. Uraemia may occur in bilateral occlusion, but is rare.
perineal and sacral pain - extension of tumour outside the bladder
enlarged pelvic lymph nodes - lymphatic spread
hepatomegaly - liver metastases
bone pain - bony metastases
General effects of malignancy:
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weight loss, anaemia, pyrexia of unknown origin
Investigations:
The investigations of choice in any patient with haematuria are:
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urinalysis - culture for bacteria, microscopy to confirm presence of red blood cells, and
cytology for malignant cells. Urine cytology enables diagnosis and grading of the
tumour in 60% of cases.
intravenous urography - upper urinary tract tumours usually appear as filling defects
in the renal pelvis or ureters. Rarely, the renal outline may be distorted. A bladder
tumour may cause ureteric obstruction. An IVU will usually demonstrate a renal
adenocarcinoma causing haematuria.
ultrasound
cystoscopy and bimanual examination under anaesthesia - critical for staging and
subsequent management
Other useful investigations are:
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full blood count, urea and electrolytes, creatinine
chest x-ray
abdominal CT - especially if radical surgery contemplated
Staging:
Grading and staging is made at cystoscopy. Any visible tumour is resected. This is sent for
histology to grade the tumour. The bladder is then washed out. A bimanual examination is
performed to determine the clinical stage. A further deep biopsy is taken. This is sent for
histology to determine the pathological stage.
Grading is either:
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G1 - well differentiated
G2 - moderately differentiated
G3 - poorly differentiated
Staging is by the TNM system. A T prefix denotes the stage as assessed clinically. A p prefix is
added when the clinical findings are supported by pathological analysis.
Pathological stages pT3 and pT4 can only be made on bladder specimens after total or partial
cystectomy.
Upper urinary tract tumours can only be staged from surgically excised specimens.
Nodal and metastatic spread is assessed only when radiotherapy or radical surgery is
contemplated.
Treatment:
Superficial:
Superficial tumours of the bladder, i.e. pTa and pT1, are mainly treated by transurethral
resection.
Intravesical cytotoxic chemotherapy using agents such as thiotepa, mitomycin, doxorubicin,
and epirubicin, may be given as adjuvant therapy, as they reduce the multiplicity and
frequency of recurrence.
If the superficial lesions are too numerous to be resected, alternative methods include:
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intravesical cytotoxic chemotherapy alone
Helmstein balloon inflation - causes pressure necrosis of tumour
Intravesical BCG immunotherapy may be required for carcinoma in situ and pT1G3 cancer.
In all cases, regular endoscopic follow up is essential.
T2 disease:
T2 tumours account for about 15% of bladder tumours.
When there is no palpable mass in the bladder wall after staging, it may be assumed that all
viable tumour has been removed. Follow-up as for superficial disease is indicated.
When thickening is palpable after staging, treatment is by external radiotherapy or less
commonly in the UK, by cystectomy. Life-long endoscopic follow-up is indicated.
If tumour is present in the bladder 6 months after radiotherapy, or recurs, treatment by total
cystectomy with urinary diversion is indicated.
T3 disease:
External radiotherapy is the treatment of choice for T3 bladder cancer as complete resection
carries the risk of bladder perforation.
Recurrence after radiotherapy, or radiotherapy complicated by bleeding, contraction,
incontinence or fistulae, is an indication for salvage cystectomy, i.e. total cystectomy removal of lower ureters, bladder, urethra, and either prostate or gynaecological organs - with
urinary diversion.
T4 disease:
Palliative radiotherapy only can be offered to control pain and haematuria with T4 staged
bladder cancer.
Prognosis:
5-year survival
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carcinoma in situ 30-40%
pTa 90-95%
pT1 40-75%
pT2 55%
pT3 25%
pT4 5-10%
Follow up:
Life-long follow-up is indicated for all bladder cancers other than stage T4, and for all upper
tract lesions.
Check cystoscopy should be performed every three months, and then, if the patient remains
tumour free, annually. After several years tumour free, cystoscopy may be replaced by annual
urine cytology