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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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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 • 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 • 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 • 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
Superficial Bladder Cancer Stages Ta/T1 • 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 • 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 • Include • 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 neo-bladder is sutured to bladder neck
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
Complications of bladder reconstruction • 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