Transcript Cabladd - Urology Information Site

Advances in the Diagnosis and
Management of Bladder Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Edith Cavell Hospital
Peterborough
Advances in the Diagnosis and
Management of Bladder Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Fitzwilliam Hospital
Peterborough
Overview
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Traditional methods of diagnosis
Current Management of bladder cancer
Advances in the diagnosis of bladder cancer
Advances in the management of bladder cancer
Diagnosis of bladder Cancer
• History
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Painless haematuria
Irritative symptoms?
[flank pain]
Other Urological problems?
Previous Urological history?
Microscopic haematuria
• Often discovered incidentally
• Urological or Nephrological cause?
• Dipsticks are sensitive, but false positives may occur
Microscopic haematuria
• Microscopy will show whether casts or protein are present
• Phase contrast microscopy helpful to determine
nephrological cause
Diagnosis of bladder Cancer
• Examination - N.B. DRE in men
• Investigations
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MSU
Urinary cytology
IVP / Renal ultrasound with KUB
Cystoscopy - Flexible vs Rigid
Management of bladder cancer
• Depends on Stage of disease
– Adequate TURBT and biopsy
– Further investigation e.g. CT
Stage of Bladder cancer at presentation
Superficial Bladder Cancer
Stages Ta/T1
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Surveillance +/- TUR or cystodiathermy
Interval at which cystoscopy takes place is variable
Rationale is to spot invasive change early
Multifocal tumours or repeated recurrence can be treated with
intravesical chemotherapy
• N.B. High grade T1 tumours are a special case - up to 50% will
become invasive
Invasive Bladder Cancer
Stages T2-T3
• Cystectomy + ileal conduit is the gold standard, but
many patients will already have micrometastases
• Radiotherapy (alone) does not cure locally invasive
disease. Neoadjuvant radiotherapy does not appear to
improve the results of cystectomy
Invasive Bladder Cancer
Stages T4 and Metastatic disease
• Chemotherapy; responses to single drugs short-lived
and incomplete
• Greater success with combination of drugs e.g. M-VAC
• Treatment is toxic but selected patients have shown
long-term and complete responses
Carcinoma in Situ
Tis / Cis
• Classified as Superficial but should be considered along
with malignant disease
• High rate of progression to invasive disease
• Once treatable only by cystectomy, now managed
initially by intravesical chemotherapy
Advances in the Diagnosis and Investigation of
Bladder Cancer
• Molecular Genetics of Bladder Cancer
• Prognostic Markers
• BTA test
Molecular Genetics of Bladder Cancer
• No single chromosome alteration consistently observed but
loss of 9q is a frequent early event - ? the site of a
suppressor gene
• Loss of chromosomes 11p and 17q are associated with
higher stage disease, ? associated with loss of p53 gene
Independent markers of progression
• Epidermal Growth Factor receptor sensitive and specific in
predicting progression in pT1G3 tumours
• p53 overexpression may serve as an important prognostic
factor for Cis
• E-cadherin can function as an invasion suppressor. Loss
of E-cadherin associated with worse prognosis
Bladder Tumour Antigen
(BTA) Test
• Detects basement membrane complexes shed into urine
by the action of tumour cell collagenases
• Latex spheres coated with modified human IgG antibodies
• Positive agglutination reaction traps blue dye, leaving
yellow dye free to migrate
Advances in the Management of Bladder
Cancer
• Intravesical Therapy
• Bladder reconstruction and replacement
• Photodynamic Therapy
Intravesical Therapy
• Indicated as prophylaxis to reduce recurrence and
tumour progression in high risk cases
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Previous recurrence
Multiple tumours
High grade tumours
Carcinoma in situ
Intravesical Therapy
• Intravesical Chemotherapy
– eg thiotepa, Mitomycin C, Doxorubicin (Adriamycin)
• Intravesical Immunotherapy
– Bacillus Calmette et Guerin (BCG)
Intravesical Chemotherapy
• 7 year data with Mitomycin C shows that
instillation at presentation after TURBT effectively
reduces risk of recurrence and risk of progression.
• Four subsequent doses at 3/12 intervals may have
further protective effect
Intravesical Immunotherapy
• BCG is an attenuated strain of M. bovis
• Believed to exert anti-tumour effect through immune
mechanism
• BCG induces a weak granulomatous response in bladder
and correlation exists between granuloma formation and
favourable response
Intravesical Immunotherapy
• Has been used for
– prophylaxis in tumour free patients
– treatment of residual tumour in patients with papillary
TCC and no Cis
– Treatment of Cis
Results of BCG treatment of Cis
• Complete response rate in short term of up to 72%
• Long term studies have reported favourable response
rates in up to 89%
• Those who fail to respond to initial therapy may respond
to more intense regimen, but failure to respond at this
stage may necessitate early cystectomy
Side effects of BCG therapy
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– Dysuria (91%)
– Frequency (90%)
– Haematuria (46%)
• Severe reactions requiring anti TB therapy occur
in 6% patients
Bladder Reconstruction and Replacement
• Advances in anaesthetic and surgical techniques
have led to alternatives to ileal conduit after
radical cystectomy
• Choices now include
– Substitution cystoplasty
– Continent diversion
Substitution Cystoplasty
• Creation of a new reservoir from bowel
segment(s)
• Ileum, ileo-caecum, or colon may be used
• Ureters implanted at proximal end and neobladder is sutured to bladder neck
Substitution Cystoplasty
Continent Diversion
• Used when neobladder can not be sutured to
bladder neck
• Tubularised ureter, ileum, or appendix used to
provide channel for catheterisation
• Neobladder emptied by intermittent catheterisation
Continent Diversion
Complications of bladder reconstruction
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Laparotomy in 10%, usually for bowel obstruction
Stone formation in 8%
Hyperchloraemic metabolic acidosis
Stomal stenosis
?Risk of tumours
Photodynamic Therapy
• Chemical photosensitisation of tumour cells, which
concentrate the photosensitiser
• Optical fibre placed in bladder down a cystoscope and
laser light stimulates the sensitised cells
• Complete response rates reported in up to 80%, but follow
up remains short
Summary
• Tumour Stage and Grade remain important
prognostic indicators but genetic information is
shedding light on tumour genesis
• Intravesical chemotherapy and immunotherapy
provides effective treatment for many superficial
bladder tumours
Summary
• Ileal conduit may be avoided by bladder
substitution or continent diversion
• Newer treatment modalities such as photodynamic
therapy may soon be available
The problem !