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1
The Role Of Surgery In The High Risk Patient
M. Wirth
Department of Urology, Technical University of
Dresden
2
Who Is At High Risk?

• PSA gt 20 ng/ml or
• clinical stage gt T2c or
• Gleason score gt 7
• gt biochemical failure gt 50 after 5 years

DAmico et al., JAMA 1998
3
PSA-relapse After RPE in Locally Advanced PCa
(n2091)


PSA-relapse (0.2 ng/ml) after 10 years
100
80
60
preop. PSA
40
20 ng/ml
20
10.1-20 ng/ml
4.1-10 ng/ml
0-4 ng/ml
0
6-
34
43
8-10
Gleason-Score
Han, Partin et al., J Urol 2003
4
Radical Prostatectomy For Locally Advanced CaP?
5
Complications of Radical Prostatectomy
(n2029, 12/1992 06/2005)
Department of Urology, TU Dresden 2006
6
Continence After RPE
Organ confined
cT3,cT4 No, N
p
Fully continent
78
80
ns
12
4
ns
Mild incontinent
Severe incontnent
10
16
ns
Gontero P. et al www.europeanurology.com
7
Positive Margins and Tumor Stage Literature
Review
8
pT Stages After RPE for Stage cT3 (n841, adj. HT
in 51 , adj. RT in 15,8 )
27
27
46
Ward et al., BJU Int 2005
9
Stage and Survival After RPE (n1255)
100
pT2pN0
pT3-4pN0
pN1
80
60
CaP-specific survival
40
Stadium
Ereignisse
Hazard-Ratio
p
10-Jahres-ÜL
pT2pN0
6/804
1
97
pT3-4pN0
12/334
5.18
0.0012
89
20
pN1
12/117
59.52
lt0.0001
83
0
0
2
4
6
8
10
12
14
Years
Dept. of Urology, TU Dresden 2006
10
Ca.- Survival After RPE for Stage cT3 (n841)
97 89 84
pT2 pT3-4 pN1
Tumor-specific survival
years
Ward et al., BJU Int 2005
11
Survival After RPE Gleason Score (n1255)
CaP-specific survival
Years after RPE
Department of Urology, TU Dresden 2006
12
Survival after RPE in Stage cT3 Role of Gleason
score (n812, adj. treatment n491 / 60)
100
Gleason score 2-6 (n307)
80
60
Overall survival
40
Gleason score 7-10 (n501)
20
p0.0001
0
2
4
6
8
10
12
14
Years
Lerner et al., J Urol 1995
13
Positive Lymph Nodes Outcome Literature review
14
PSA and Recurrence After RPE (n2477)
No PSA progression
50
Months
Chun et al., World J Urol 2006
15
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
16
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
17
Independent Predictors of Survival After RPE
(n1302)
or not classified, n47.
(not significant pN0 vs. pN1, PSA lt10 vs. 10
ng/ml)
Dept. of Urology, TU Dresden 2006 (presented at
DGU 2006)
18
Retropubic vs. Laparoscopic RPE Outcome In High
Risk Patients (Gleason-Score 8-10)
100
laparoscopic (n82)
retropubic (n188)
80
60
Guillonneau et al., J. Urol. 2003
Mian et al., J. Urol. 2002
PSA-free survival (PSA-cutoff 0.1 ng/ml)
40
?
20
0
0
5
10
0
5
10
Years after RPE
19
Outcome In Clinically Locally Advanced CaP
According To Chosen Treatment (1971-1984,
n2311)
100
80
60
prostate cancer-specific survival
40
radical prostatectomy
external beam radiotherapy
watchful waiting
20
0
2
4
6
8
10
12
Years after onset of treatment
Barry et al., Cancer 2001
20
Radical Prostatectomy for cT4 Disease (n1093,
SEER database)
Johnstone et al., Cancer 2006
21
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22
Survival After RPE for Clinically Not Organ
Confined CaP (n751)

• Not distinguishable concerning CaP- specific
  and overall survival
• Supports our decision to perform surgery
  for stage T3 disease

Sweat, Zincke et al., J Urol 2002
23
Combined Treatment?

• Neoadjuvant HTRPE
• RPEadjuvant HT
• RPEadjuvant RTX
• RPEadjuvant RTXadjuvant HT
• Chemotherapy?

24
Neoadjuvant Hormonal Therapy?
25
Downstaging of Locally Advanced to Organ
Confined CaP By Neoadjuvant HT
Literature review
Authors
n
downstaged to pT1/2
Hellström et al. (1999)
35
50
Pummer et al. (1994)
25
4
Labrie et al. (1994)
15
73
Schulman et al. (1994)
15
27
Fair et al. (1993)
55
26-40
Kennedy et al. (1992)
7
29
Flamm et al., (1991)
21
33
Morgan et al. (1991)
36
11
Thompson et al. (1991)
24
13
Schröder and van den Ouden, World J Urol 2000
26
PSA-free Survival After Neoadjuvant HT


Literature review
Scolieri et al., J Urol 2000
27
PSA-relapse-free After 7 years
Cyproteronacetate vs. Control (n213)
PSA
CPA
control
p
(ng/ml)
0-10
97
96
0.2
10-20
90
96
0.4
gt20
53
35
0.015
Klotz et al., J Urol 2003
28
Adjuvant Hormonal Therapy?
29
Adjuvant Hormonal Therapy After RPE Overview
survival
progression
regimen
stage
author, year
benefit
benefit
orchiectomy or LHRH- analog
pN
Messing et al., 1999, 2003
no data available
benefit
LHRH- analog
stage C
Prayer-Galetti et al., 2000
no difference
benefit
flutamide
pT3-4pN0
Wirth et al., 2004
no difference
benefit
bicalutamide
T1b-T4
Mc Leod et al., 2006
30
Adjuvant Hormonal Therapy After RPE for pN-PCa
(n98, FU 11.9 Jahre)
Messing et al., Lancet Oncol 2006
31
Prospective Randomised Study Flutamide vs.
Control After RPE In Stage pT3-4 pN0
recurrence-free survival
survival
100
100
80
80
60
60
40
40
Flutamide, n152
20
20
control, n157
log-rank-Test, p0.0041
log-rank-Test, p0.92
0
0

0
100
200
300
400
500
600
0
100
200
300
400
500
600
weeks after RPE
Wirth et al., Eur Urol 2004
32
EPC-Program Objective Progression (n8116, FU
7.4 y)
McLeod et al., BJU Int 2006
33
EPC-Program Overall Survival (n8116, FU 7.4 y)
McLeod et al., BJU Int 2006
34
Adjuvant Radiation Therapy ?
35
Adjuvant Radiotherapy After RPE (ARO 96-02 / AUO
AP 09/95 , pT3R0-1, PSA 0, n108)

100
plt0.0001, hazard ratio 0.4
80
60
81
no PSA relapse at 4 years
40
60
20
0
Adjuvant RTX (60 Gy)
no adjuvant RTX
Wiegel et al., ASCO 2005
36
Adjuvant Radiotherapy After RPE (EORTC Trial
22911, pT3 or R1, n1005)
100
plt0.0001
80
60
no local recurrence
40
adjuvant radiotherapy
watchful waiting
20
0
0
1
2
3
4
5
6
7
8
9
10
Years
Bolla et al., Lancet 2005
37
Summary

• Best concept unknown (lack of randomized studies)
  
• Complications after RPE seem to be similar in pT2
  and pT3
• Outcome after RPE is better than expected in the
  past
• The role of adjuvant treatment in locally
  advanced disease is still unclear
• Wide spectrum in biological behavior of locally
  advanced disease
• Refined patient selection (new prognostic
  markers) of paramount concern

38
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39
Summary
Best concept unknown (lack of studies) Good
results after RPE/RT/-adjuvant treatment Wide
spectrum in biological behavior of locally
advanced disease Refined patient selection (new
prognostic markers) of paramount
concern Nomogramms may improve clinical staging
40
Postoperative nomogram to predict failure after
RPE
Kattan et al., J Clin Oncol 1999
41
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
42
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
43
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
44
Outcome of Surgery for Clinical Unilateral T3a
Prostate Cancer (n200, adj. treatment n44 /
22)
Hsu et al., Eur Urol 2006
45
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46
PSA velocity and mortality after RPE (n1.095)
tumor-specific mortality
Years after RPE
DAmico et al., NEJM 2004
47
Positive margins and tumor stage literature
review
48
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