Bladder Cancer

Tomáš Novotný

…so that's the problem…

Bladder cancer:

Epidemiology• Incidence: 20/100000/year (Europe)• Mortality: 8-9/100000/year

• Fourth most common cancer in men– Incidence: 31.1 mortality: 12.1

• Thirteenth most common cancer in women– Incidence: 9.5 mortality: 4.5

• At diagnosis >70%: > 65 y of age

Bladder cancer:

Epidemiology

• Male:female 2.8:1• High prevalence / incedence increasing,

mortality stabilizing, recurence ability /

Bladder cancer: Aetiology• Smoking – 4x increased risk

– Causes 50% of cases

• Occupational – rubber/dye industry– Napthylamine, benzidine

• Schistosomiasis, chronic infection

• Medications – cyclofosfamid, fenacetin

Bladder cancer: Histology

• 90-95% transitional-cell carcinoma

• 3% squamos-cell carcinoma• 2% adenocarcinoma• <1% small-cell carcinoma

• 99% primary tumors

Bladder cancer: Entities

• 75-85% superficial bladder cancerpTa, pTis, pT1

• 10-15% muscle-invasive bladder

cancerpT2, pT3, pT4

• 5% metastatic bladder cancerN+, M+

Bladder cancer:

Presentation• Classically painless frank haematuria,

sometimes intermittent

• Frequent urination, urgency

• symptoms with involvement of neighboring organs /kidneys, lymphoedema, pelvic pain…/

Bladder cancer: Examination

• History

• Physical examination

• Urine examination / urinalysis, cultivation, cytology – can be only 60% sensitive/

• Ultrasound

Bladder cancer: Examination• Cystoscopy is mandatory

• Biopsy or TURBT

• Bimanual pelvic examination /before and after TURBT/

• Chest X-ray• IVU – no routinely, (5% chance upper

tract involvement)

Bladder cancer: Stage and Prognosis

• Ta – confined to the epithelium, no invasion through basement membrane – common

• Tis – carcinoma in situ – aggressive (grade 3) cells confined to epithelium – 50% progression risk

• T1 – invades lamina propria• T2 – invades bladder muscle• T3 – outside bladder• T4 – adjacent organs involved

Bladder cancer: Stage and Prognosis

Bladder cancer: Stage and Prognosis

Stage TNM 5-y. Survival

0 Ta/Tis NoMo >85%

I T1 NoMo 65-75%

II T2a-b NoMo 57%

III T3a-4a NoMo 31%

IV T4b NoMo 24%each T N+Mo 14%each T M+ med. 6-9 Mo

Bladder cancer: Grade (WHO 1973)

• Grade 1 – well differentiated – good prognosis

• Grade 2 – moderately differentiated

• Grade 3 – poorly differentiated– Least common– Most progress to invasive disease

Bladder cancer: Grade (WHO/ISUP 1998)

• PNLMP - papilar neoplasia low malignant potential

• LG - papillary carcinoma of low-grade malignancy

• HG - papillary carcinoma of high-grade malignancy

Carcinoma in situ (CIS)• Precursor infiltrating tumors• Primary or secondary

• Subjectively – frequent urination, urgency, cystalgia

• Objectively – no pathologies• Laboratory

– Microhematuria– Cytology positive (PAP IV-V)

CIS diagnosis• Cystoscopy

– Pink areas– Random biopsy– Fluorescent cystoskopy

CIS treatment

• Primary CIS: BCG

• Secondary CIS: TURB + BCG

• Recurrent CIS /after therapy/: cystectomy

Bladder cancer: Treatment

• Superficial Bladder CancerpTa, pT1, Tis

• Invasive bladder cancer pT2-pT4

Superficial Bladder Cancer

pTa, pT1, Tis

• Standard of care=intravesical therapy transurethral resection bladder tumors /TURBT/

• Relapse rate: 70% adjuvant therapy

TURBT

TURBT

TURBT

TURBT – bladder perforation

Superficial Bladder Cancer

• Histological grading is important

G1 G2 G3

Relapse rate 42% 50% 80%

Progression rate 2% 11% 45%

Superficial Bladder Cancer

Adjuvant Therapy• Reduces relapse rate by 30-80%

– Mitomycin C – in patient with intermediate-risk BT

– BCG – in patient with CIS, high risk BT

Invasive bladder cancer

• Standard of care = Radical cystectomy with pelvic lymphadenectomy

Only about 50% of patients with high-grade invasive disease are cured

Radical cystectomy

Results of radical cystectomy

Stage Recurrence-Free Overall Survival5 y. 10y. 5 y. 10y.

T2 N- 89 87 77 57N+ 50 50 52 52

T3a N- 78 76 64 44N+ 41 37 40 26

T3b N- 62 61 49 29N+ 29 29 24 12

T4a N- 50 45 44 23N+ 33 33 26 20

Stein et al JCO 2001;19:666

Radical cystectomy

Chemotherapy for bladder cancer

• Bladder cancer is a chemosensitive disease

• Active single agents.

RR– Cisplatin 30%– Carboplatin 20%– Gemcitabine 20-30%– Ifosfamide 20%

Chemotherapy for bladder cancer

Combination chemotherapy.

RR CR

– MVAC 40-75% <20%– Gemzar / Cisplatin 40-70% 5-15%– Gemzar / Carboplatin 65% 5%– Taxol / Carboplatin 20-40%

Adjuvant chemotherapy

• Six randomised trials have compared CT with observation after cystectomy or RT

• 4x no survival benefit• 2x benefit from adjuvant CT no standard of care

– node positive disease, lymphovascular invasion, positive margins

Neoadjuvant chemotherapy

• Meta-analysis of ten randomised trials (2688 patients)

13% reduction in risk of death5% absolute benefit at 5 yearsOS increased from 45% to 50%

ABC Meta-analysis Collaboration. Lancet 2003;361:1927

Combined Radio- and Chemotherapy

CR 5y.OS

• Radiotherapy 57% 47%

• RT and cisplatin 85% 69%

• RT and carboplatin 70%57%

Birkenhake et al. Strahlenther Onkol 1998;174:121

Bladder-sparing therapy for invasive bladder cancer

• High probability of subsequent distant metastasis after cystectomy or radiotherapy alone (50% within 2 years)

• Radiotherapy in comparison with cystectomy has inferior results (local control 40%)

• muscle-invasive bladder cancer is often a systemic disease

combined modality therapy

Bladder-sparing protocol

Transurthral resection

Induction Therapy: Radiation + chemotherapy

(cisplatin, paclitacel)

Cystoscopy after 1 month

no tumor tumor

Consolidation: RT + CT cystectomy

Bladder-sparing protocol

Shiply et al. Urology 2002;60:62

T2: 5y / 10y OS: 74% / 66%

T3-T4a: 5y / 10y OS: 53% / 52%

Combined-modality treatment and organ preservation in invasive

bladder cancer

• Rödel et al. JCO 2002;20:3061

• Complete remission 72%• Local control after CR 64% (10 y.)

• distant metastasis 35% (10 y.)

• Disease-specific survival 42% (10 y.)

• Preservation of bladder >80%

….so, the bladder had removed

…and urine, how to get it out…?

Urinary diversion

• Diversion of urinary pathway from its natural path

• Types:– Temporary– Permanent

A nephrostomy is a surgical procedure by which a tube, stent, orcatheter is inserted through the skin into the kidney

Cutaneous Ureterostomy…

•One kidney drainage, with short-live prognosis

•Complications (infection, stone, stenosis)

Permanent urinary diversion

• Uretero – sigmoidostomy

• Ileal conduit

• Colon conduit

• Ileocaecaecal segment

Cutaneous urinary diversions

Ileal conduit (ileal loop)A 12 cm loop of ileum led out through abdominal wallStents used The space at cystectomy site drained by a drainage systemAfter surgery a skin barrier and a transparent disposable urinary drainage bagConstantly drains

Complications of ileal conduit

• Wound infection • Wound dehiscence• Urinary leakage• Ureteral obstruction• Small bowel obstruction • Ileus• Stomal gangrene• Narrowing of the stoma• Pyelonephritis • Renal calculi

Continent Urinary Diversions

• Continent Ileal Urinary ReservoirIndiana Pouch• Most common continent urinary

diversion• Periodically catheterized Koch PouchUreterosigmoidostomy • Voiding occurs from rectum

Uretero-sigmoideostomy

Uretero- sigmoidostomy

• Complications:– Reflux of urine

– Hyperchloraemic acidosis (ammonium chloride reabsorption, bicarbonates secretion)

– Renal infection

– Stricture formation

Potential complications

• Peritonitis due to disruption of anastomosis

• Stoma ischaemia and necrosis due to compromised blood supply to stoma

• Stoma retraction and separation of mucocutaneous border due to tension or trauma

Bladder reconstruction

Thank you for attention