1. 1 LINFOADENECTOMIA Alessandro Volpe Università del Piemonte Orientale
AOU Maggiore della Carità, Novara 1

2. LND IN RENAL CANCER
The value of LND in patients with renal cell carcinoma (RCC) still remains controversial
No data have clearly demonstrated which candidates should undergo LND and which template should be used for LND in RCC surgical management
Many urologists have abandoned systematic and standardized LND at the time of nephrectomy because of the lack of a proven benefit

6. 6

7. 7

8. 8

9. 383 RN+LND vs. 389 RN alone OUTCOMES Time-to-progression
Overall survival
Progression-free survival
383 RN+LND
vs.
389 RN alone

12. pN+ = 4%

13. Low-risk population
All cN0
patients

14. Prognostic implications of nodal metastasis
Positive nodes have been clearly shown to have an independent adverse effect on oncologic outcome, regardless of other prognostic factors
The estimated cancer specific survival rates at 1, 5, and 10 yr following radical nephrectomy for patients with pN1 RCC are 52– 72%, 21–38%, and 11–29%, respectively
Patients with nodal involvement have a 7.8-fold greater chance of dying from their disease than those without nodal involvement
Lymph node stage has even an impact on the survival of patients with established metastatic RCC
Lughezzani G et al. Cancer 2009;115:5680–7
Blute ML et al. J Urol 2004;172: 465–9

15. LNI rates increase with tumor stage

16. Mean tumor diameter (mm)
when one notes that presently there is no curative adjuvant therapy.
Extended LND
cN+ LND
No LND n
531 (51%)
199 (19%)
305 (30%)
LN removed 18 6 3
p<0.001
Mean age (ys) 55 60 66
Mean tumor diameter (mm) 81 77 64
pT3ab (%) 56 47
p<0.05
Furhman G3 (%) 30 25 21
5 years CSS (%) 70 61 65
p<0.01
10 years CSS (%) 58 50 44

19. Can we predict LNI ? - Non standardized LND in 415 cN0 patients
- 5 risk factors:
Tumor size > 10 cm
Fuhrman 3-4
Sarcomatoid component
pT3-pT4
Histologic tumor necrosis
169 high-risk patients
LNI 38%

21. cN+ patients “Histologically positive nodes were found
in only 42% of patients with
enlarged nodes at preoperative CT”

22. M+
patients

24. “Patients who can potentially be cured by LND
have early lymph node metastasis
and no systemic disease”
Canfield et al., J Urol 175: , 2006 24

25. LND in RCC. Which template?
Predilection of RCC for early haematogenic dissemination
≈57% TanyN0M1
Directly to the thoracic duct ≈30%
Many possible different lymphatic routes in normal retroperitoneal anatomy
Collateral lymphatic drainage and invasion of tissue with different lymphatic drainage (e.g. perinephric fat)
Isolated metastases in the ipsilateral iliac and supraclavicular nodes ≈10%

26. RCC: LYMPH NODE LANDING SITES

28. Distribution of first landing sites with direct tracer injection28

29. Some cases of sentinel nodes from RCC outside the known templates
RCC = renal cell carcinoma. 29

31. LND IN RCC: TEMPLATE Lymph node dissection (LND) should include:
- (a) for the right kidney, the paracaval, retrocaval, and precaval nodes from the adrenal vein to the level of the inferior mesenteric artery
- (b) for the left kidney, the para-aortic and preaortic nodes from the crus of the diaphragm to the inferior mesenteric artery
- Interaortocaval nodes (overlapping purple area) should always be removed as well when extended LND is sought

32. as pN + increased with the number of lymph nodes examined
as pN + increased with the number of lymph nodes examined. In RCC, >12 lymph nodes need to be assessed for optimal staging.

33. p=0.02
In conclusions,
C.Terrone et al ,Eur Urol. 2006 33

34. BACKGROUND AND OBJECTIVES
The optimal classification for lymph node staging in RCC is still debated.
Aim of the study was to assess the prognostic value of the number of positive LNs using different cut-offs (0 vs. 1 vs. >1 LN+; 0 vs. 1-4 vs >4 LN+).
PATIENTS AND METHODS
1550 patients underwent radical nephrectomy and lymphadenectomy for RCC
3 tertiary care centers (Milan, Turin, Novara)
November December 2012
Prognostic value of the number of LNs:
2009 TNM classification (0 vs. 1 vs.>1 LN+) vs. new proposed classification (0 vs. 1-4 vs >4 LN+)
Age
Follow up (months)
LNs removed
LNs involved
Median
60.0
57.6 7 3
IQR
52-68
18-130
4-12
1-6
pN0
pN+
Tot
pT1a
196 1
197
pT1b
363 12
375
pT2a
172 15
187
pT2b 75 11 86
pT3a
335 79
414
pT3b
154 35
189
pT3c 23 17 40
pT4 25 37 62
1343
207
1550 %
pN1 61
3.9
pN2
146
9.4
pN0
pN+
Tot
cM0
1145
111
1256
cM1
198 96
294
1343
207 34

35. Regressor HR
95% CI p
pN (1 vs 0)
1.31
( )
0.119
pN (2 vs 0)
2.76
( )
<0.001
pT (2 vs 1)
2.04
( )
pT (3 vs 1)
3.20
( )
pT (4 vs 1)
6.30
( )
cM (1 vs 0)
4.91
( )
Grade (High vs Low)
1.60
( )
RESULTS
The 2009 TNM classification correlates significantly with 5-year CSS only in M1 pts, but not in Mall and M0 pts.
The proposed classification correlates significantly with 5-year CSS for Mall and M1 pts, but not for M0 pts.
Regressor HR
95% CI p
pN (1 vs 0)
1.90
( )
<0.001
pN (2 vs 0)
2.58
( )
pT (2 vs 1)
2.07
( )
pT (3 vs 1)
3.17
( )
pT (4 vs 1)
6.11
( )
cM (1 vs 0)
4.71
( )
Grade (High vs Low)
1.62
( )
CONCLUSIONS
The number of positive lymph nodes correlates with prognosis after RN in RCC, especially in patients with distant metastases.
The current TNM classification of nodal involvement should be modified.

36. n = 850; TanyN0–1Many RCC + LND (1987-2011)
90% 15
nodes