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 neo-

bladder 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 !