Sin ttulo de diapositiva

1
Disease profiling in superficial bladder cancer
Dr. Eduardo Solsona Service of
Urology Instituto Valenciano de Oncología
(IVO) Valencia. Spain
2
Table 1. Recurrence, progression and survival in
SBC
Mean follow-up
Authors (yr.)
No.pts.
Criteria
Recurrence
Progression
Death
Mulders (94)
387
Ta-1, G1-3, primary
2,25 yrs.
37,2
2,2
Kurth (95)
576
Ta-1, G1-3
4 yrs.
54
13
22
Kiemeney (93)
1674
Ta-1, G1-3, primary
3,5 yrs.
55
10
Herr (97)
88
Recurrent, high risk
gt15 yrs.
49
28,4
Millan (00)
1529
Ta-1, G1-3, primary
4.2 yrs
48
7,3
4,4
Pawinski (96)
2535
Ta-1, G1-3
4.6 yrs.
51
15
35
Solsona (00)
191
T1G3, Ta-1Tis
6.5 yrs.
72,7
47,6
18,6
3
Table 2. Univariate analysis prognostic factors
Authors (yr.)
Clinical factors
Recurrent
Culter (82)
Mean time interval
Dalesio (83), Kurth (95), Loening (80)
Recurrence/year
Lutzeyer (82)
Recurrent
Multiplicity
Culter (82), Dalesio (83) , Lutzeyer(80), Parmar
(89), Heney (83)
Culter (82), Narayana (83), Takashi (87), Dalesio
(83), Loening (80),
Size
Henney (83), Parmar (89)
Localisation
Stephenson (90), De Mulder (94)
Pathological factors
Malmtröm (89), Takayashi (87), Lutzeyer (82),
Narayana (83), Loening (80)

Stage
Henney (83), Lipponen (90), Schappers (90)
Culter (82), Dalesio (83), Loening (80), Narayana
(80), Takayashi (87),
Grade
Henney (83) , Lipponen (90), Flamm (89)
Bladder Tis associated
Henney (83), Utz (70), Smith (83), Vicente (90),
Solsona (91), Flamm (89)
Prostate Involvement
Sthephenson (90), Matzkin (96), Solsona (95),
Herr (97)
Cytogenetic factors
DNA ploidy
Malmström (89), Koss (89), Murphy (86), De
Vere-White (88), Norming (89)
Chromosome abnormalities
Falor (88), Sandberg (77), De Vere-White (88),
Pauwels (88)
Blood Groups Antigens
ABO (H)
DeCenzo (75), Lange(78), Newman (80), Johnson
(80), Fujita, Pauwels (88)
Lewis X antigen
Sheinfeld (92), Cordon-Cardo (88)
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Table 3. Multivariate analysis Prognostic
factors for recurrence
Independent significant variables
Bladder
3-month
Authors (yr.)
No.pts.
No.
Stage
Grade
Recurrent
Size
Localisation
Tis
cystoscopy
Loening (80)
178
Yes
Parmar (89)
305
Yes
Yes
De Mulder (94)
371
Yes
Yes
Kiemenney (93)
1674
Yes
Yes
Millan (00)
1529
Yes
Yes
Yes
Kurth (95)
535
Yes
Yes
Yes
Yes
Yes
Witges (92)
1026
Yes
5
Table 4. Multivariate analysis Prognostic
factors for progression
Independent significant variables
Bladder
First
Authors (yr.)
No.pts.
No.
Stage
Grade
Recurrent
Size
Localisation
Tis
cystoscopy
Herr (89)
221
Yes
Malmström (89)
195
Yes
Kiemeney (93)
1674
Yes
Yes
Yes
Yes
Millan (00)
1529
Yes
Yes
Yes
Kurth (95)
535
Yes
Yes
Yes
Yes
Yes
Solsona (97)
1243
Yes
Yes
Yes
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Table 5. Multivariate analysis Prognostic
factors for survival
Independent significant variables
Bladder
Authors (yr.)
No.pts.
Age
Stage
Grade
Recurrent
Size
Sex
Tis
Flamm (90)
345
Yes
Yes
Takayasi (87)
264
Yes
Yes
Yes
Kuth (95)
535
Yes
Yes
Yes
Yes
Millan (00)
1529
Yes
Yes
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Table 6. Prognostic factors for risk groups
multivariate analysis for
establishing risk groups.
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Table 7. Risk groups
No. pts 1529 primary superficial bladder
tumours. Multivariate analysis
Recurrence
Progression
Mortality
Risk groups (criteria)
rate
rate
rate
Low ( TaG1, T1G1 unique)
0
37
0
Intermediate (T1G1 multiple, TaG2,T1G2 unique)
45
1.8
0
High (T1G2 multiple, G3, Tis)
54
15
9.5
Millán M. J.Urol, 2000
Low risk single, Ta, G1, ? 3 cm.
diameter High-risk T1, G3, multifocal or highly
recurrent, CIS (TIS) Intermediate-risk all
other tumours, Ta-1, G1-2, multifocal, gt 3 cm
diameter

Guidelines on Bladder Cancer (2002)
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Table 8. Risk groups recurrence and progression
Risk groups
Recurrence ()
Progression ()
Incidence (range)
32 -40
Low
36.5 (29-48)
3.3 (0-7.1)
30 -42
Intermediate
57.2 (45-67)
9.4 (1.8-17.4)
6 -43
High
73.5 (54-82)
31.5 (15-47.6)
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Table 9. Risk groups Basic therapy strategy
Low -primary Avoid overtreatment
-secondary Reduce recurrence
Intermediate -primary Reduce recurrence
-secondary Prevent or delay progression
Decrease toxicity
High -primary Prevent or delay
progression -secondary Decrease toxicity
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Table 10. Molecular markers uni multivariate
analysis
Molecules
Univariate analysis
Multivariate analysis
Proliferating Antigens
Fontana (92), Tsujuhashi (91),
Asakura (97) , Popov (93)
.Ki-67
Cohen (93) (recurrence)
(recurrence)
.PCNA
Cohen (93), Vet (96) (recurrence)
Growth Factors
.EGF
Neal (90) (progression)
Cellular adhesion m.
Banks (96), Griffiths (95), Lpponen (95)
.E-Cadherin
(recurrence, progression)
Angiogenesis
Bochner (97),OBrien (95)
.Microvessel density
(recurrence, progression)
Suppressor genes
.Rb
Cordon-Cardo (92) (progression)
Lipponen (93), Cordon-Cardo (94),
Keegan (98), Lipponen (98),
.p53
Esrig (94), Sarkis (94) (progression)
Lee (97) (progression)
.p21
Stein (98) (recurrence, progression)
.bcl-2
Wolf (01) (progression)
Oncogenes
.c-H-ras
Fontana (96) (recurrence)
Underwood (95), Moriyana (91),
.c-erB-2
Moch (93) (progression)
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Table 11. RCT indication Predictive factors for
progression
Microstaging (T1a/T1b/T1c) 1.- Predictive
value for progression Younes (90), Hasui (94),
Angulo (95), Holmang (97), Smits (98)
2.- No predictive value for progression
Zellwerger (99)



The reproductibility of these stratifications has
been questioned since interobserver agreement
was only 52 to 67 (Holmang -97, Engel -92)


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Table 12. Timing of RCT Predictive factors for
progression
High risk group response to intravesical therapy
Response
Pathological
Progression
Number Patients
Author (yr.)
Therapy
interval
pattern
()
Merz (95)
115
BCG
9 months
no response
82.6
Bono (94)
128
ADM
1st evaluation
no response
50
Oversen (90)
60
BCG
3-6 months
no response
77
no response (T1, positive cytology)
Herr (91)
221
BCG
3-6 months
79-100
no response (T1,G3, Tis, prostate invasion)
Solsona (00)
191
BCG/MMC
3 months
82.8
independent factor in multivariate analysis
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Table 13. Timing of RCT Predictive factors for
progression
High risk group (bladder Tis) response to BCG
plus p53 expression
Author (yr.)
p53 status
Number Patients
Progression
Died of tumour
Lacombe (96)
(-)
15
2 (13)
1 (7)
()
17
14 (83)
7 (41)
Ick (97)
(-)
8 0 (0)
()
4
3 (75)
independent factor in multivariate analysis
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Table 14. Conclusions
1. The most useful prognostic factors for
recurrence and progression are stage, grade,
recurrent character, bladder Tis associated
and multifocality. 2. Based on these prognostic
factors, three risk groups of patients can
be identified in which a different therapeutic
strategy can be considered. 3. Molecular
markers are new promising prognostic factors,
but currently dont have enough
reliability. 4. In high risk patients, clinical
response to intravesical therapy can be an
important predictive factor for progression and
in non-responders pathological pattern or
p53 overexpression can be potential
indicators for early cystectomy.