Miss Jo Cresswell Miss Jo Cresswell Consultant Urologist Consultant Urologist James Cook University Hospital, Middlesbrough James Cook University Hospital, Middlesbrough Overview of Intravesical Therapy: Current Overview of Intravesical Therapy: Current Controversies Controversies
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Overview of intravesical therapy: Current Controversies
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Miss Jo CresswellMiss Jo Cresswell
Consultant UrologistConsultant Urologist
James Cook University Hospital, Middlesbrough James Cook University Hospital, Middlesbrough
Overview of Intravesical Therapy: Current Overview of Intravesical Therapy: Current ControversiesControversies
Overview
Intravesical, Oct 2010
Intravesical Therapy
Single Immediate Instillation
Maintenance Chemotherapy
BCG Failure T1G3
Single instillation of intravesical chemotherapy
Single instillation of MMC: Always appropriate?
Intravesical, Oct 2010
Single instillation of intravesical chemotherapy
“One immediate post-operative instillation of chemotherapy should be given in all patients after TUR of presumably non-muscle invasive bladder cancer.”(EAU Guidelines, 2009, Level 1a evidence)
↓ risk of recurrence by 50% at 2 years
OR 39% reduction in recurrence with single instillation
48.4% versus 36.7%, median FU 3.5 yrs
(Metanalysis Sylvester et al, J Urol 2004)
However, 50% of European urologists, and 4% in USA routinely..
Intravesical, Oct 2010
MMC in UK – timing.....MMC in UK – timing.....
Within 24 hours - evidence from literature
Within 6 hours – recommended by EAU
Immediate intra-op instillation(Mostafid et al, 2006)
A prospective study of the accuracy of flexible cystoscopy:
Haematuria clinic
89 new tumours (10 MI, 79 NMIBC)
Prospective study
Cystoscopists asked to indicate if NMIBC or muscle-invasive
Cp to TURBT histology
Sensitivity 90%,Specificity 85%
Those incorrectly assessed as MI – T1
Prev studies Herr et al, 93% accurate for low grade recurrence
NMIBC, May 2010
Prediction of stage and grade
Single instillation for all new tumours.....Single instillation for all new tumours.....
An accepted standard of care
Surely not controversial .........
RCT cp single instillation of epirubicin vs no instillation
219 patients. ↓Risk of recurrence by 15%
BUT no benefit for intermediate/high risk tumours(Gudjonsson et al, 2009)
Overall 8.5 pts receive instillations to prevent 1 recurrence
often small, low risk
Adds time, expense, side effects for small gain(Herr, 2009)
NMIBC, May 2010
Single instillation of intravesical chemotherapy
A new EAU recommendation.....A new EAU recommendation.....
‘‘A single instillation of a chemotherapeutic agent after TUR should be administered only in primary, solitary, low-grade NMIBC.”(Brausi, 2010)
Intermediate risk tumours should be given course of maintenance BCG, chemotherapy if not tolerated (and no immediate instillation is required)
NMIBC, May 2010
Single instillation of intravesical chemotherapy
Immediate instillation after TURBT for recurrence....
Mechanism of action of MMC:
Destruction of circulating cancer cells
Prevention of seeding into disrupted urothelium
Surely this is effective after TURBT for recurrence.....
(Grey et al, BJMSU, 2009 – small study, no difference)
(Gudjonsson et al, 2009 -no benefit for recurrent tumours)
?Intra-operative instillation followed by course of MMC
NMIBC, May 2010
Single instillation of intravesical chemotherapy
Re-resection of high grade disease
Re-resection of high-grade disease: a question of quality?
•Accurate staging/Grading•Removal of macroscopic disease
NMIBC, May 2010
Which cases warrant early re-resection?
T1 -Yes
Ta - ??
Muscle present - ?No
EAU Guidelines:
“A second TUR should be considered when the initial resection was incomplete, or when the pathologist has reported that the specimen contained no muscle tissue. Furthermore, a second TUR should be performed when a high-grade, non-muscle invasive tumour or aT1 tumour has been detected at the initial TUR.”
Re-resection of high grade disease
NMIBC, May 2010
What is the evidence to support this recommendation?What is the evidence to support this recommendation?
• Residual disease on re-resection
Ta/cis 31%, T1 51.7%
(Herr et al, 1999)
Ta 27-72%, T1 33-78%
(Babjuk, 2009)
• Understaging
T1: up to 40% upstaged to T2 on cystectomy
(Dutta et al, 2001)
TaG3 (5%), T1G3 (30%)
(Herr et al, 2008)
NMIBC, May 2010
Re-resection of high grade disease
•↓effectiveness of adjuvant treatment
•Understaging of disease→ inappropriate treatment
•Poorer prognosis
Re-resection of high grade disease
Effect on prognosisEffect on prognosis
• RCT cp routine re-resection to initial TUR only in T1 disease
Progression in 6.5% cp to 23.5%
(Divrik et al, 2010)
• Can re-resection compensate for initial incomplete resection?
Progression may be worse even after re-resection
NMIBC, May 2010
Re-resection of high grade disease
Most important risk factor for understaging was absence of muscle
• Muscle absent in 30-50% specimens
• M’Boro data
Muscle present in 45.8-67.3% of G3
↑with seniority of surgeon
(Jesuraj et al, 2008)
• Understaging:
If muscle present 30%
If muscle absent 64%
(Dutta et al, 2001)
NMIBC, May 2010
Even if muscle present, high-grade disease warrants re-resection
Re-resection of high grade disease
Decisions for re-resection?
• No muscle present – Tx
• TaG3/T1G3
• Review of path slides, discuss at MDT
• Presence of lymphovascular invasion, micropapillary variants
• Conflicts with imaging
• Patient characteristics
Young patients, fit for radical treatment
Older, unfit patients – risk vs benefit
NMIBC, May 2010
Quality of TURBT
NMIBC, May 2010
• Variation in recurrence rates between institutions
7.4-45.8%
(Brausi et al, 2002)
Persistant disease
due to variability in quality of TUR
• Presence of detrusor muscle a measure of quality of TUR?
Very popular concept
Possible standard for audit/competence?
Presence of detrusor muscle:
Reduces risk of recurrenceDM – 21% RR FFCNo DM – 44.4%Even for small, low grade tumours(Mariappan et al, 2010)
Dependent on operator experienceJunior – 56.8%Senior – 72.6%
Effect of training:
RR 28% for juniors
8% for seniors
With training ↑DM, and ↓Rec(Brausi et al, 2008)
Reasons for inadequate TUR?
Lack of experience
Fear of perforation
Perforation 1.3-3.5% (Nieder et al, 2005)
On cystography 58.3% (Balbay, 2005)
NMIBC, May 2010
Quality of TURBT
Quality of TUR
What is a successful TURBT?What is a successful TURBT?
No lesions missed (PDD)
Staging assessed correctly
Without complications
“Larger, high grade lesions should be resected by seniors”(Mariappan et al, 2010)