Download Bladder Cancer

Bladder Cancer
Tomáš Novotný
…so that's the problem…
Bladder cancer:
• Incidence:
• Mortality:
Epidemiology
20/100000/year (Europe)
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%
• 2%
• <1%
squamos-cell carcinoma
adenocarcinoma
small-cell carcinoma
• 99%
primary tumors
Bladder cancer:
Entities
• 75-85% superficial bladder cancer
pTa, pTis, pT1
• 10-15% muscle-invasive bladder cancer
pT2, pT3, pT4
• 5%
metastatic bladder cancer
N+, 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
II
T1
T2a-b
NoMo
NoMo
65-75%
57%
III
T3a-4a
NoMo
31%
IV
T4b
NoMo
24%
each T
each T
N+Mo
M+
14%
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 highgrade 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 Cancer
pTa, 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 highgrade invasive disease are cured
Radical cystectomy
Results of radical cystectomy
Stage
T2
T3a
T3b
T4a
NN+
NN+
NN+
NN+
Recurrence-Free
5 y.
10y.
Overall Survival
5 y.
10y.
89
50
78
41
62
29
50
33
77
52
64
40
49
24
44
26
87
50
76
37
61
29
45
33
57
52
44
26
29
12
23
20
Stein et al JCO 2001;19:666
Radical cystectomy
Chemotherapy for bladder cancer
• Bladder cancer is a chemosensitive disease
• Active single agents.
–
–
–
–
Cisplatin
Carboplatin
Gemcitabine
Ifosfamide
RR
30%
20%
20-30%
20%
Chemotherapy for bladder cancer
Combination chemotherapy.
–
–
–
–
MVAC
Gemzar / Cisplatin
Gemzar / Carboplatin
Taxol / Carboplatin
RR
CR
40-75%
40-70%
65%
20-40%
<20%
5-15%
5%
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 death
5% absolute benefit at 5 years
OS 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
Consolidation: RT + CT
tumor
cystectomy
Bladder-sparing protocol
T2: 5y / 10y OS: 74% / 66%
T3-T4a: 5y / 10y OS: 53% / 52%
Shiply et al. Urology 2002;60:62
Combined-modality treatment and organ
preservation in invasive bladder cancer
• Rödel et al. JCO 2002;20:3061
•
•
•
•
•
Complete remission
Local control after CR
distant metastasis
Disease-specific survival
Preservation of bladder
72%
64% (10 y.)
35% (10 y.)
42% (10 y.)
>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, or
catheter 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 wall
Stents used
The space at cystectomy
site drained by a drainage
system
After surgery a skin
barrier and a transparent
disposable urinary
drainage bag
Constantly 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 Reservoir
Indiana Pouch
• Most common continent urinary
diversion
• Periodically catheterized
Koch Pouch
Ureterosigmoidostomy
• Voiding occurs from rectum
Ureterosigmoideostomy
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