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