Post on 12-Jan-2016
description
Lymphadenectomy in the surgical treatment of prostate cancer - does it influence survival?
Oliver HakenbergUrologische Klinik und Poliklinik
Universitätsklinikum Rostock
Incidence and mortality of prostate cancer in Europe 1998
Davidson & Gabbay, WHO Report 2007
Pelvic lymphadenectomy
• Node-positive prostate cancer is a systemic disease
• Surgery should be aborted if pelvic lymph nodes are positive
trends in risk stratification of surgically treated prostate cancer (CaPSURE)
Cooperberg et al, J Urol 2003, 170, S21ff
temporal trends in RPERetrospective studyn=37 centres5291 patients
Stage shift
PSA-recurrence = 36%
Chun & Djavan et al, Eur Urol 2007, 52, 1067-75
Lymphadenectomy - pros and cons
• Pro– A significant percentage of patients will harbour N+ disease
– Better staging with LAE
– LAE in limited N+ will be curative
• Con– Overtreatment in most patients
– Associated with morbidity
– No influence on outcome
Incidence of pN+ in RPE
n pN+
Allaf, 2004 4000 2.2%
Masterson, 2006 5038 3.8%
Burckhard, 2002 463 26%
Briganti, 2007 858 10.3%
Weckermann, 2007 1055 19.6%
Burckhardt et al, Eur Urol, 2002Allaf et al, J Urol 2004Masterson et al, J Urol 2006Briganti et al, Urology 2007Weckermann & Wawroschek et al, J Urol 2007
Partin tables for the preoperative predictionof pathologic stage
Partin tables for the preoperative predictionof pathologic stage
Difference in Gleason Score: original vs. reference pathologyDifference in Gleason Score:
original vs. reference pathology
0,12 0,592,64
10,56
25,02
45,71
12,73
2,330,25 0,04 0,01
0
5
10
15
20
25
30
35
40
45
50
-5 -4 -3 -2 -1 0 1 2 3 4 5
Abweichung von Referenz
Häu
fig
keit
(%
)
Validation of the Partin tables for the prediction of an organ-confined cancer
Validation of the Partin tables for the prediction of an organ-confined cancer
Blute et al. J Urol 164, 2000Blute et al. J Urol 164, 2000
0
20
40
60
80
100
0 20 40 60 80 100
Mayo
Line of equalityLine of equality
Predicted % organ confined by Partin tablesPredicted % organ confined by Partin tables
May
o %
org
an c
onfin
edM
ayo
% o
rgan
con
fined
n=2.295n=2.295
Sentinel nodes and radio-guided surgery
n pN+ Outside standard PLND
Jeschke et al, 2005
71 12.9% 73%
Weckermann et al, 2007
1055 19.6% 63%
Jeschke et al, J Urol 2005 Weckermann & Wawroschek et al, J Urol 2007
Lymphocelesclinical series
n
Viville 1994 1288 8.5%
Hautmann 1994 418 0.2%
Noldus 1997 511 11%
Augustin 2003 1243 without PLAD
with PLAD
0.3%
4.3%
Heinzer 1998 320 4.7%
Paul 2004 57 19%
Lymphocelesby imaging studies
• 33% with ultrasound
• 27% with ultrasound
• 61% with CT scanning
Hakenberg et al, Eur Urol 2005Spring et al, Radiology 1981Solberg et al, Scand J Urol Nephrol 2003
• n= 446 consecutive RPEs• pelvic U/S and venous duplex sonography on days 0, 8 and
21• 146 pelvic lymphoceles (size 1-20 cm) - 32.7%
– 18.7% day 8, 27.9% day 21 – only 26 with venous thromboses, 13/26 with measurable reduction in venous flow
• 73 patients with venous thromboses - 16.4%– 7.2% day 8, 10.5% day 21.– 3 patients with distal thromboses (calf muscles) were diagnosed preoperatively– majority of thromboses was distal and small – DVTs: day 8 n=4, day 21 n=10 – pulmonary emboli: day 8 n=2, day 21 n=2
• A reduction in venous flow was seen only in patients with lymphoceles
Hakenberg et al, Eur Urol 2005
Extent of PLND
• Limited (standard) = obturator fossa
• Modified = + internal iliac artery
• Extended = + common iliac artery
Standard PLND underestimates nodal disease
• n = 100 standard vs n= 103 extended PLND
Heidenreich et al, 2002
PLND standard extended
nodes (mean)
11 28
pN+ 12% 26%
Standard PLND underestimates nodal diseaselaparoscopic RPE
Stone et al, 1997Touijer & Guilloneau, 2006
n nodes(mean) pN+
Stone et al, 1997Modified
extended
1899.3
17.8
7.3%
23.1%
Touijer et al, 2006Limited
extended
2129
14 RR 21.2
pN+ disease in Berne n= 365-463 consecutive RPE patients, 50.6% pT2
n PSA nodes pN+
Bader et al, 2002 365 11.9
(0.4-172)
21 24% Internal iliac artery 58%
Obturator 34%
Exclusively internal iliac 19%
Burckhard et al, 2002
463 11.0 21 24% PSA < 10: 12%
PSA < 20: 17%
PSA < 10 and Gleason < 7: 0%
PSA < 10 and Gleason < 8: 10%
Bader et al, 2003 367 Follow-up: 45 months (13-141)
19 (22%) DOD
Disease-free survival
with 1 pN+ 39%
with = 2 pN+ 10%
with> 2 pN+ 14%Bader et al, J Urol, 2002Bader et al, J Urol, 2003Burckhardt et al, Eur Urol, 2002
But…contemporaray RPE
• n= 123
• Limited vs extended PLND on either side
• PSA 7.4 ng/ml, 72% cT1c– Extended: 4 pN+– Limited: 3 pN+
Clark et al, 2003
Extent of PLND and pN+ yield• n= 858• PSA 5.8 ng/ml• 55% pT1c, 41% pT2• 14 nodes (mean)• 10.3% pN+
– 2-10 nodes: 5.6% pN+– 20-40 nodes: 17.6% pN+
• no of nodes examined predicted for pN+: p<0.001– < 10 nodes examined: 0% probability of pN+– > 28 nodes: 90% probability of detecting pN+
Briganti et al, Urology 2007
Volume of N+ disease and progressionn Volume of N+
diseaseothers
Cheng et al, 1998
269 RPE patients
significant Gleason score
Cancer volume
DNA ploidy
Daneshmand et al, 2004
235 pN+ patients significant RR of clinical recurrence compared to N-
Golimbu et al, 1987
43 D1 patients with median FU > 5 years
significant 1 N+ vs > more N+
Cheng et al, Am J Surg Pathol 1998Daneshmand et al, J Urol 2004Golimkbu et al, Urology 1987
Influence of PLND with limited N+ -disease on PFS
Surgeon 1 extended PLND
Surgeon 2limited PLND
n 2135 1865
nodes 11.6 8.9 p<0.001
pN+ 3.2% 1.1%<15% nodes +
5-yr PSF survival 43% 10%
Allaf et al, J Urol 2004
Influence on survival?
n PSA recurrence
Bhatta Dhar, 2004
Low risk PCa
with PLND
without PLND
140
196
14%
12%
Berglund, 2007
CaPSURE
with PLND
without PLND
4963
No significant difference
Influence on survival?
n nodes
Masterson, 2006 5038 mean 9
(3.8% positive)
No of nodes removed correlated with bNED in node-negative patients
DiMarco, 2005 7036 mean
14 (1987) to 5 (2000)
No correlation of no of nodes and PSA-progression
Conclusions
• PLND carries morbidity• many positive nodes are outside obturator fossa• the more nodes removed the more likely the detection of
positive nodes• no influence of limited PLND on survival• influence of extended PLND on PFS is unclear but likely• extent of PLAD should depend on case and case mix• low risk PCa (Gleason < 7 and PSA < 10 ng/ml) does not
need PLAD