Prostatakarzinom

Prostatakarzinom
Dr. med. Daniel Nguyen
Urologische Klinik
Inselspital, Bern
Prostate Cancer -­‐ Prevalence High Intermediate Low Prävalenz in Autopsiestudien
Autopsy Prevalence Rates of Prostate Cancer Worldwide (%)
Age (Yrs)
US White
US Black
Spain
Japan
Greece
Hungary
21-30
8
8
4
0
0
0
31-40
31
31
9
20
0
27
41-50
37
43
14
13
2.6
20
51-60
44
46
24
22
5.2
28
61-70
65
70
32
35
13.9
44
71-80
83
81
33
41
30.9
58
81-90
0
0
0
48
40
73
Total
34.6
35.9
18.5
20.5
19.9
38.8
51-60: 28%
61-70: 43%
Epidemiologie
• 
Schweiz:
152/100‘000 Neuerkrankungen/Jahr (5446 Männer 2007)
36/100‘000 Todesfälle/Jahr (24%, 1302 Männer 2007)
• 
USA:
16% Risiko Diagnose Prostatakrebs
3% Risiko Tod durch Prostatakrebs
< 20% sterben am Prostatakrebs, wenn unbehandelt
Statistik des jährlichen Bevökerungsstandes (ESPOP) 2006, Bundesamt für Statistik 2007
Krebs in der Schweiz: Wichtige Zahlen, Schweizerische Krebsliga 2007
H.B. Carter, N Engl J Med, 350(33):2292-4;2004
Screening: bei wem?
•  Männer ab 50 Jahren mit einer
Lebenserwartung >10 Jahren
•  Bei positiver Familienanamnese ab 45 Jahren
•  In Abhängigkheit der Therapiebereitschaft
•  Kein Screening ab 70–75 Jahren
•  Intervallen 2-3 Jahre
Prostate Specific An<gen (PSA) •  “organspezifisch”: Prostata normal 0.1 ng/ml/g Gewebe BPH 0.3 ng/ml/g Gewebe Prostatakarzinom
3.5 ng/ml/g Gewebe •  hormonelle Faktoren (Proscar®, Avodart®)
•  Infek<onen A. Stamey et al., J. Urol., 141:1076, 1989 J. Amiel et al., Ann Urol., 23:528, 1989 Warum PSA? confined Carcinoma Organ •  < 4 ng/ml 5-­‐10% > 60% •  4 -­‐ 10 ng/ml 20 % 50 % •  10 -­‐ 20 ng/ml 50 % 35 % •  > 20 ng/ml > 50% < 20 % Par<n et al., JAMA, 277: 1445-­‐1451, 1997 Probability of finding Prostate cancer according to serum PSA and the pa<ent‘s age Total PSA (ng/mL) Age(yr) 4.0-­‐10.0 10.1-­‐20 45-­‐55 22% ( 349) 27% ( 68) 56-­‐65 29% (1211) 35% (246) 66-­‐75 34% (1479) 40% (460) >75 45% ( 346) 62% (139) Total 32% (3385) 41% (913) Key: PSA = prostate-specific antigen.
*Malignancy rate (number of cases). Carlson G.D. et al., Urology 52:455-­‐461,1998 Andere Gründe für eine PSA –
erhöhung
zwischen 4 bis 10 ng/ml
•  Prostatitis
•  Zystitis, Harnretention
•  Katheterismus, Prostatamassage,
Biopsien
•  Sehr grosse BPH (0.03ng PSA/ml/ ccm
BPH)
Prevalence of Prostate Cancer among Men with a PSA Level ≤4.0 ng per Milliliter PSA Level
No. of Men
(N=2950)
Men with Prostate
Cancer
(N=449) (15.2 %)
no. of men (%)
≤0.5 ng/ml
486
32 (6.6)
0.6 - 1.0 ng/ml
791
80 (10.1)
1.1 - 2.0 ng/ml
998
170 (17.0)
2.1 - 3.0 ng/ml
482
115 (23.9)
3.1 - 4.0 ng/ml
193
52 (26.9)
I.M. Thompson et al., N Engl J Med 350:2239-­‐2246, 2004 Prostate Cancer Preven<on Trial Placebo Group No. at No. Included No. Positive PSA level at
Random- in Analysis for Prostate study entry
ization
Cancer (%)
0.0 - 1.0 ng/
4639
2196
357 (16.3)
ml
1.1 - 2.0 ng/
3311
1647
457 (27.7)
ml
2.1 - 3.0 ng/
1506
848
332 (39.2)
ml
I.M. Thompson et al., N Engl J Med 349:215-­‐224, 2003 Propor<on of screen-­‐eligible American men of different age groups who would be labeled abnormal by prostate-­‐specific an<gen (PSA) threshold PSA > 2.5 ng/mL Propor<on abnormal 40% 30% PSA > 4 ng/mL 20% PSA > 6 ng/mL 10% 0% 40 -­‐ 49 50 -­‐ 59 60 -­‐ 69 70 -­‐ 79 Age groups (years) PSA > 8 ng/mL PSA > 10 ng/mL 10-­‐year risk of prostate cancer death > 80 Conclusion: Lowering the PSA threshold to 2.5 ng/mL would double the number of men defined as abnormal. Un<l there is evidence that screening is effec<ve, increasing the number of men recommended for prostate biopsy would be a mistake. H.G. Welch et al., J Natl Cancer Inst, 97:1132-­‐1137, 2005 0022-5347/04/1724-1297/0
The Journal of Urology®
Copyright © 2004 by American Urological Association
0000139993.51181.5d
Vol. 172, 1297-1301, October 2004
Printed in U.S.A.
DOI:10.1097/01.ju.
Oncology: Prostate/Testis/Pernis/Urethra
THE PROSTATE SPECIFIC ANTIGEN ERA IN THE UNITED STATES IS OVER
FOR PROSTATE CANCER: WHAT HAPPENED IN THE LAST 20 YEARS ?
THOMAS A. STAMEY, MITCHELL CALDWELL, JOHN E. McNEAL, ROSALIE NOLLEY, MARCI
HEMENEZ,
AND JOSUA DOWNS
From the Department of Urology, School of Medicine, Stanford University, Stanford, California
Results: Most parameters decreased linearly during the 20 years, including
palpable nodules on digital rectal examination from 91% to 17%, mean age from 64
to 59 years, mean serum PSA from 25 to 8 ng/ml, and index (largest) cancer volume
from 5.3 to 2.4 cc. Percent Gleason grade 4/5 of the largest cancer averaged 27% to
35% and prostate weight 44 to 53 gm. Contrasting August 1983 to December 1988
with January 1999 to July 2003, 6 histological cancer parameters had statistically
significant relationships to serum PSA in the first period. In the last 5 years serum
PSA was related only to prostate size.
Conclusions: Serum PSA was related to prostate cancer 20 years ago. In the last
5 years serum PSA has only been related to benign prostatic hyperplasia. There is an
urgent need for serum markers that reflect the size and grade of this ubiquitous
cancer.
The value of the serum level of the prostate-­‐ specific an<gen in prosta<c pathology Théodon P, Rymer JC, Chopin D, Kouyoudjian JC, Abbou CC, Auvert J. Service d'Urologie, Hôpital Henri-­‐Mondor, Creteil. Development of serum assays for prostate-­‐specific an<gen (PSA) has provided physicians with a new marker for carcinoma of the prostate. PSA was compared to prostate acid phosphatases (PAP), the reference serum marker, in 162 pa<ents including 54 pa<ents with carcinoma of the prostate (CP), 84 pa<ents with benign hypertrophy of the prostate (BHP), and 24 controls free of prostate disorders. PSA appeared more sensi<ve but less specific than PAP. Results showed that PSA is not suitable for rou<ne screening in the popula<on at large where BPH is common. Ann Urol 22:199-­‐205, 1988 Preopera<ve serum prostate specific an<gen levels between 2 and 22 ng./ml correlate poorly with post-­‐radical prostatectomy cancer morphology 315 100 PSA (ng/ml) 31.5 10 3.2 1 0.1 0.3 3.2 1 10 Cancer Volume (cc) 31.5 100 315 Conclusions: Preopera<ve serum PSA has a clinically useless rela<onship with cancer volume and grade in radical prostatectomy specimens. Th. A. Stamey et al., J. Urol., 167:103-­‐111, 2002  PSA is no good discriminator in small
volume disease
Prostate specific Antigen
1 gr of normal prostatic tissue:
serum
1 gr of BPH tissue:
serum
1 gr of prostate cancer:
prostate cancer of 0.5 ml
serum
(significant)
0.1 ng/ml
0.3 ng/ml
3.5 ng/ml serum
1.75 ng/ml
3-­‐Gläser-­‐Probe: Ausschluss Prosta<<s ca. 200 ml später Doxycyclin 2 x 100 mg/d/2 wks., 1 x 100 mg/d/2 wks. PSA 6 weeks aqer treatment Digitally-­‐guided fine-­‐
needle puncture Ultrasound-­‐guided transrectal biopsy Risikostratifizierung bei Männern
mit lokalisiertem Prostatakarzinom
PSA
Low risk
Intermediate risk
High risk
Gleason score
Klinisches
Stadium
<10ng/ml
und
<6
und
T1 T2a
10-20ng/ml
oder
7
oder
T2b T2c
>20ng/ml
oder
8 10
oder
T3 T4*
* Klinisches Stadium T3 T4 = lokal fortgeschritten
Rule out metastasis •  CT Abdomen / Becken •  Bone scan •  Chest x-­‐ray Wer braucht Therapie?
Rate per 100,000 person-years (ESR)
Prostate cancer
trends in incidence & mortality
110
100
PSA
90
80
70
60
50
40
30
20
10
Year of diagnosis/mortality
Source Eindhoven Cancer Registry (IKZ) © 05-04-2006
Inzidenz
Mortalität
Welchem Patienten mit bioptisch
diagnostiziertem Prostatakarzinom sollte zur
Therapie mit kurativer Absicht geraten
werden?
•  Lebenserwartung mehr als 10 Jahre
•  Signifikantes Tumorvolumen (>0.5 ml Karzinom)
•  (mässig) agressiver Typ ( ab Gleason score 6)
Indikationen:
cT1-T2 Nx M0 G1-3
(cT3 Nx M0 G1-3)
What is the size of so called
„significant disease“? (> 0,5ml)
Diameter Radius Volume 1mm 0.5mm 0.004ml 5mm 2.5mm 0.06ml 10mm 5.0mm 0.5ml Organ begrenzt / Nicht Organ begrenzt
Partin et al. JAMA 1997, 277:1445
Natürlicher Krankheitsverlauf
(55-59y)
100
80
60
Gleason Score 6
40
Alive %
20
Survival
0
Non-Prostate Cancer Mortality
Prostate Cancer Mortality
100
80
n=767
60
Gleason Score 9
40
20
0
0
5
10
15
20
years
Albertsen CP, JAMA. 2005 May 4;293(17):2095-101. (modifiziert)
Prevalence of Prostate Cancer among Men with a PSA Level ≤4.0 ng per Milliliter 4.0 PSA (ng/ml) 3.0 2.0 1.0 0.0 Gleason Gleason Gleason Gleason Gleason Gleason Score 4 Score 5 Score 6 Score 7 Score 8 Score 9 (N=12) (N=47) (N=302) (N=60) (N=4) (N=3) Prosta<c-­‐Specific An<gen (PSA) Values among the 449 Men with Prostate Cancer, According to the Gleason Score. I.M. Thompson et al., N Engl J Med 350:2239-­‐2246, 2004 Organ begrenzt / Nicht Organ begrenzt
Stromale Invasion
Periprostatische
Invasion
Perineurale Invasion
Therapieoptionen beim lokalisierten
Prostatakarzinom
•  Wait and Watch
Resultate von Patientenserien mit
„Active Surveillance“
Autor
Anzahl
Probanden
Mittleres Alter
(Jahre)
Follow-up
(Monate)
% auf
surveillance
verbleibend
Krebsspezifische
Mortalität (%)
Klotz
299
Not given
64
60
0.7
Soloway
99
66
46
92
0
Carter
407
66
34
59
0
Dall‘era
321
63
43
63
0
Van As
326
67
22
73
0
Roemeling
278
70
41
71
0
Therapieoptionen beim lokalisierten
Prostatakarzinom
•  Wait and Watch
•  Radikale Prostatektomie
Allgemeines Überleben
A
0.4
Radical prostatectomy
Probability
Watchful waiting
0.3
0.2
0
No. At risk
Radical prostatectomy
Watchful waiting
P = .09.
0.1
0
2
4
6
8
Years
10
12
347 343 332 311 284 220 142
348 341 326 306 267 201 127
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Tod durch Prostatakarzinom
B
0.4
Radical prostatectomy
Watchful waiting
0.3
0.2
P = .03
0.1
0
No. At risk
Radical prostatectomy
Watchful waiting
0
2
4
6
8
Years
10
12
347 343 332 311 284 220 142
348 341 326 306 267 201 127
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Lokale Progression
0.6
Radical prostatectomy
Watchful waiting
Probability
0.5
0.4
P < .001
0.3
0.2
0.1
0
No. At risk
Radical prostatectomy
Watchful waiting
0
2
4
6
8
Years
10
12
347 330 310 278 246 186 112
348 311 261 203 168 119 71
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Hormonelle Therapie
0.6
Radical prostatectomy
Watchful waiting
0.5
0.4
P < .001
0.3
0.2
0.1
0
No. At risk
Radical prostatectomy
Watchful waiting
10
12
347 317 284 250 215 165
348 309 261 206 157 112
92
68
0
2
4
6
8
Years
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Allgemeine Mortalität
Probability
0.4
0.3
0.2
P = .004
0.1
0
No. At risk
RP, Age > 65
RP, Age < 65
WW, Age > 65
WW, Age < 65
RP, Age > 65
RP, Age < 65
WW, Age > 65
WW, Age < 65
0
3
190
157
182
166
185
154
177
157
6
Years
166
145
162
144
9
12
121
127
123
105
59
83
64
63
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Tod durch Prostatakarzinom
Probability
0.4
0.3
0.2
P = .01
0.1
0
No. At risk
RP, Age > 65
RP, Age < 65
WW, Age > 65
WW, Age < 65
RP, Age > 65
RP, Age < 65
WW, Age > 65
WW, Age < 65
0
3
190
157
182
166
185
154
177
157
6
Years
166
145
162
144
9
12
121
127
123
105
59
83
64
63
Bill-Axelson A. et al., J Natl Cancer Inst 2008;100: 1144 – 1154
Vorteile und Nachteile der radikalen
Prostatektomie
•  Möglichkeit der ausgedehnten pelvinen
Lymphadenektomie
•  Geringer Blutverlust, ökonomisch
•  gute funktionnelle und onkologische
Ergebnisse
•  Kurze Lernkurve, das Ergebnis hängt
jedoch von der Erfahrung des Operateurs
ab
•  Kurze Operationszeit
Vorteile und Nachteile der radikalen
Prostatektomie
•  Erektile Dysfunktion 40 bis 90%
•  Tropfenweise Harninkontinenz 5 bis 20%
Ausgedehnte pelvine Lymphadenektomie
1
2
3
Pelvic Lymphadenektomy How extensive ? Localized Extensive (externa, obturatoria) (externa, obturatoria, value interna, communis, No of removed LN präsakral) 9.3 17.8 % posi<ve LN 7.3 % 23.1 % No of Pa<ents 150 39 (Median) N.N. Stone et al., J. Urol., 158: 1891, 1997 < 0.05 0.02 Pelvic Lymphadenektomy No of removed LN Standard LA Extended LA n=100 n=103 11 (6 – 19) 28 (21 – 48) Incidence of posi<ve LN 12 % 26 % Pre-­‐op PSA 14.9 (1.6 – 109) 15.9 (1.2 – 129) A. Heidenreich et al., J Urol 167: 1681, 2002 463 Pa<ents with P-­‐CA N0 M0 •  PSA (Median): 11.2 µg/L (0.4 -­‐ 172) •  extended pelvic lymphadenektomy •  Retropubic Radical Prostatektomy 109 (24%)  (pN+) 21 (6-­‐50) LK per pa<ent removed Urologische Universitätsklinik Bern, Schweiz Posi<ve Lymphknoten beim Prostata-­‐Ca 12% 21% 17% Bei 64/109 (59%) Pat. N+ entlang der iliakal internen Gefässe Without resec<on of lymph nodes in A. iliaca interna-­‐region 17% of pa<ents with posi<ve LN understaged and in 59% of posi<ve LN resp. 14% of all pa<ents posi<ve LN would be leq in situ Urologische Universitätsklinik Bern, Schweiz Prostatakarzinom with local LN-­‐
Metastases Longterm survival possible ? Bexer survival in pN+? n = 156, 1975 -­‐ 1989 Tumor-­‐spezific
P survival (Median)
LA +
nur LA
RPE 1 or 2 posi<ve LN
0.015 10.2 J
5.9 J
≥ 3 posi<ve LN
0.734 6.0 J
5.3 J
Pa<ents with low lymphogenic tumor-­‐load Frazier et al., World J Urol 12: 308, 1994