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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 Stage of Bladder cancer at presentation 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 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 • • • • • 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 !
