Transcript Vesical TCC - Prostate S

Management of T1G3
Bladder cancer
Dr Charles Chabert
T1G3
High grade lesion with invasion between
epithelium & muscularis propria
Gene alterations similar to T2 TCC
Dilemma is to identify which will be cured
by TUR & which will progress
Turner E Urol 45 (2004) 401-405
Natural History T1G3
Paucity of data on natural history of
untreated T1G3
Recurrence rates 50-70%
Progression rate 25-50%
Heney et al J Urol 1983; 130:1083-6
Diagnosis & Initial
Management
Is it really T1G3?
Ensure muscle present
Cold cut biopsies
Flourescence endoscopic resection
Second TUR
Retrospective review of concordance of
2nd TURBT
2nd TURBT changed management in
33%
If no muscle 49% upstaged to T2
J Urol 1999; 146: 316-8
Second TUR
Residual tumour present in 33-37%
Grade & stage predictive of residual
tumour
Biopsy abnormal urothelium
Soloway et al Urol Clin N Am (2005) 133-145
Staging System
Recommendation to substage T1
121 T1 G3
T1a : above muscularis mucosae
T1b: below muscularis mucosae
Only 6% not substaged
5yr survival 54% vs 42%
Holmang et al J Urol 1997: 157; 800-3
Staging System
Categorised to T1a, T1b & T1c
No difference in 3 yr risk of recurrence
Risk of progession
6%, 33% & 55%
ROP x27 if T1c & CIS
Smits et al Urol 1998;86:1035-43
Staging System
Measured the depth of invasion
55 patients
Measured from the BM to the deepest tumour
cell
Cutoff 1.5mm
PPV >T2 95%
Cheng et al. Cancer 1999:86:1035
Prognostic Features
Early recurrence after TUR & BCG
Size
Multifocality
CIS
Prostatic Urethra
LVI
Depth of Lamina Propria Invasion
Rodriguez J urol 2000;163:73-8
Perioperative Cytotoxic
Chemotherapy
60-80% recurrence at 5 years
If high grade, there is risk of progression
Perioperative Cytotoxic
Chemotherapy
Meta-analysis:
One-dose immediate postop cytotoxic
chemotherapy
Sylvester et al J Urol2004: 171;2186-90
Materials & methods
Randomised trials with primary or
recurrent Ta/T1
Exclusion of CIS
Sylvester et al J Urol 171, June 2004
Materials & Methods
Primary end point:
% of patients with a recurrence in the 2
treatment arms
Decrease in Odds of recurrence
calculated without time to recurrence
Sylvester et al J Urol 171, June 2004
Results
12 trials considered
5 exclusions;
4 inadequate randomisation
1 included CIS
7 trials entered into Meta-analysis
Sylvester et al J Urol 171, June 2004
Trial Characteristics
Accural between 1981-1994
Median F/U: 3.4 years (2-10.7 yrs)
3 trials included only primary patients
2 trials only single tumours
Sylvester et al J Urol 171, June 2004
Trial Characteristics
4 different drugs used
Epirubicin 3 trials
Mitomycin C 2 trials
Thiotepa 1 trial
Pirarubicin 1 trial
Sylvester et al J Urol 171, June 2004
Patient Characteristics
1517 eligible patients from 7 trials
1476 had F/U
748 (50.7%) TUR only & 728 (49.3%)
TUR + instillation
Sylvester et al J Urol 171, June 2004
Tumour Characteristics
Predominantly low risk
89.2% primary tumours
84.3% single tumours
67.9% Ta
9.5% G3
Sylvester et al J Urol 171, June 2004
Recurrence
629 (42.6%) of 1476 patients
362 (48.4%) TUR & 267 (36.7%)
TUR + Chemo
Decrease of 39% in odds of recurrence
Sylvester et al J Urol 171, June 2004
Toxicity
Mild irritative bladder symptoms in 10%
Systemic toxicity extremely rare
Allergic skin reactions 1-3%
Sylvester et al J Urol 171, June 2004
Summary
NNT to prevent 1 recurrence:
8.5
One instillation cost effective
Significantly reduces recurrence with
minimal morbidity
Sylvester et al J Urol 171, June 2004
Immunotherapy
BCG results in local immunological
response
Helper T-cells
Cytotoxic t-cell activation
Soloway et al Urol Clin N Am (2005) 133-145
T1G3
BCG era “Rule of threes”
1/3 survive with bladder
1/3 survive without bladder
1/3 die of their disease
Studer et al J Urol 2003; 169:96-100
Merits of BCG
Davis et al
59% of 98 patients bladder retention at 10
years
Herr HW
50% preservation with 15 year F/U
Turner E Urol 45 (2004) 401-405
Merits of BCG
Maintenance BCG
SWOG data: reduced recurrence
Poor tolerance with regimen 17%
completion rate
Lamm et al J Urol 2000;163:1124
Role of Cystectomy: Early
vs Late
Conservative management associated
with lifelong risk of recurrence,
progression & metastasis
Studer et al J Urol 2003; 169:96-100
Role of Cystectomy: Early
vs Late
Series of 153 patients
Recurrence rate 75% at 10 years
30% dead at 10 years
Studer et al J Urol 2003; 169:96-100
Role of Cystectomy: Early
vs Late
Delay in treatment affects survival:
Cystectomy within or greater 3 months
55% vs 34% 5 year survival
May et al scand J Urol Neph 2004
Role of Cystectomy: Early
vs Late
Improved 15 year survival with early
cystectomy
Review of 90 patients
Cut off 2 years
Herr et al J Urol 2001,166:1296-9
Role of Cystectomy: Early
vs Late
Immediate cystectomy if :
Young
Deep T1
One additional poor prognostic feature
Summary
Highly malignant tumour
Variable & unpredictable behaviour
Accurate staging & re –TUR
Intravesicle immunotherapy
Early cystectomy