Introductions: The objective of this study was to determine the prognostic value of positive lymph nodes (LNs) in patients with renal cell carcinoma (RCC) and tumor thrombus (TT) and to explore risk factors predicting LNs metastasis. Methods: We retrospectively analyzed 216 patients with RCC and TT treated at a single institution from January 2015 to December 2019. Overall survival (OS) and progression-free survival (PFS) was estimated using the Kaplan-Meier curves divided by pathological LN status. Associations between clinicopathological features and survival outcomes were evaluated using Cox regression models. Logistic regression model was performed to determine risk factors associated with LN metastasis. Results: We identified 216 patients with RCC and TT including 85 (39.4%) who did and 131 (60.6%) who did not undergo lymph node dissection. Pathologically positive LNs were found in 18 (8.3%) cases. pN1 had significant worse OS (median: 21 vs. 41 and 56 months, p < 0.001) and PFS (median:14 vs. 29 and 33 months, p < 0.001) than pN0 and pNx respectively. However, survival outcomes of OS and PFS were similar between pNx-0/M1 and pN1/M0 group and between 1- and ≥2-node-positive group. Non-CCRCC (p = 0.001), sarcomatoid differentiation (p < 0.001), and pathologically positive LNs (p = 0.025) were independent prognostic predictors predicting worse OS while distance metastasis (p = 0.009), non-CCRCC (p = 0.023), necrosis (p = 0.014), sarcomatoid differentiation (p = 0.003), and pathologically positive LNs (p = 0.007) were independent prognostic indicators predicting worse PFS. Clinically positive LNs (p = 0.014) and sarcomatoid differentiation (p = 0.009) were predictors of positive LNs. Conclusions: LNs metastasis independently associated with worse survival outcomes in RCC and TT populations, with similar survival outcomes compared to distance metastasis. Therefore, more accurate risk stratification is warranted for guiding postoperative surveillance and adjuvant therapy.

1.
Blom
JH
,
van Poppel
H
,
Maréchal
JM
,
Jacqmin
D
,
Schröder
FH
,
de Prijck
L
, et al.
Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881
.
Eur Urol
.
2009
;
55
(
1
):
28
34
. .
2.
Bhindi
B
,
Wallis
CJD
,
Boorjian
SA
,
Thompson
RH
,
Farrell
A
,
Kim
SP
, et al.
The role of lymph node dissection in the management of renal cell carcinoma: a systematic review and meta-analysis
.
BJU Int
.
2018
;
121
(
5
):
684
98
. .
3.
Gershman
B
,
Thompson
RH
,
Moreira
DM
,
Boorjian
SA
,
Tollefson
MK
,
Lohse
CM
, et al.
Radical nephrectomy with or without lymph node dissection for nonmetastatic renal cell carcinoma: a propensity score-based analysis
.
Eur Urol
.
2017
;
71
(
4
):
560
7
. .
4.
Marchioni
M
,
Bandini
M
,
Pompe
RS
,
Martel
T
,
Tian
Z
,
Shariat
SF
, et al.
The impact of lymph node dissection and positive lymph nodes on cancer-specific mortality in contemporary pT(2–3) non-metastatic renal cell carcinoma treated with radical nephrectomy
.
BJU Int
.
2018
;
121
(
3
):
383
92
.
5.
Whitson
JM
,
Harris
CR
,
Reese
AC
,
Meng
MV
.
Lymphadenectomy improves survival of patients with renal cell carcinoma and nodal metastases
.
J Urol
.
2011
;
185
(
5
):
1615
20
. .
6.
Capitanio
U
,
Becker
F
,
Blute
ML
,
Mulders
P
,
Patard
JJ
,
Russo
P
, et al.
Lymph node dissection in renal cell carcinoma
.
Eur Urol
.
2011
;
60
(
6
):
1212
20
. .
7.
Capitanio
U
,
Suardi
N
,
Matloob
R
,
Roscigno
M
,
Abdollah
F
,
Di Trapani
E
, et al.
Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC)
.
BJU Int
.
2014
;
114
(
2
):
210
5
. .
8.
Gershman
B
,
Moreira
DM
,
Thompson
RH
,
Boorjian
SA
,
Lohse
CM
,
Costello
BA
, et al.
Renal cell carcinoma with isolated lymph node involvement: long-term natural history and predictors of oncologic outcomes following surgical resection
.
Eur Urol
.
2017
;
72
(
2
):
300
6
. .
9.
Tilki
D
,
Chandrasekar
T
,
Capitanio
U
,
Ciancio
G
,
Daneshmand
S
,
Gontero
P
, et al.
Impact of lymph node dissection at the time of radical nephrectomy with tumor thrombectomy on oncological outcomes: Results from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC)
.
Urol Oncol
.
2018
;
36
(
2
):
e11
79
. .
10.
Srivastava
A
,
Rivera-Núñez
Z
,
Kim
S
,
Sterling
J
,
Farber
NJ
,
Radadia
KD
, et al.
Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer
.
Cancer
.
2020
;
126
(
13
):
2991
3001
. .
11.
Golijanin
B
,
Pereira
J
,
Mueller-Leonhard
C
,
Golijanin
D
,
Amin
A
,
Mega
A
, et al.
The natural history of renal cell carcinoma with isolated lymph node metastases following surgical resection from 2006 to 2013
.
Urol Oncol
.
2019
;
37
(
12
):
932
40
. .
12.
Capogrosso
P
,
Larcher
A
,
Nini
A
,
Muttin
F
,
Cianflone
F
,
Ripa
F
, et al.
The critical role of lymph node dissection in selecting high-risk nonmetastatic renal cancer candidates for adjuvant therapy after nephrectomy
.
Urol Oncol
.
2019
;
37
(
4
):
293
e30
. .
13.
Lardas
M
,
Stewart
F
,
Scrimgeour
D
,
Hofmann
F
,
Marconi
L
,
Dabestani
S
, et al.
Systematic review of surgical management of nonmetastatic renal cell carcinoma with vena caval thrombus
.
Eur Urol
.
2016
;
70
(
2
):
265
80
. .
14.
Wagner
B
,
Patard
JJ
,
Méjean
A
,
Bensalah
K
,
Verhoest
G
,
Zigeuner
R
, et al.
Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma
.
Eur Urol
.
2009
;
55
(
2
):
452
9
. .
15.
Miyake
H
,
Terakawa
T
,
Furukawa
J
,
Muramaki
M
,
Fujisawa
M
.
Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus
.
Eur J Surg Oncol
.
2012
;
38
(
7
):
630
6
. .
16.
Yang
B
,
Xia
H
,
Xu
C
,
Lu
M
,
Zhang
S
,
Wang
G
, et al.
Impact of sarcomatoid differentiation and rhabdoid differentiation on prognosis for renal cell carcinoma with vena caval tumour thrombus treated surgically
.
BMC Urol
.
2020
;
20
(
1
):
14
. .
17.
Neves
RJ
,
Zincke
H
.
Surgical treatment of renal cancer with vena cava extension
.
Br J Urol
.
1987
;
59
(
5
):
390
5
. .
18.
Edge
SB
,
Compton
CC
.
The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM
.
Ann Surg Oncol
.
2010
;
17
(
6
):
1471
4
. .
19.
Al Otaibi
M
,
Abou Youssif
T
,
Alkhaldi
A
,
Sircar
K
,
Kassouf
W
,
Aprikian
A
, et al.
Renal cell carcinoma with inferior vena caval extention: impact of tumour extent on surgical outcome
.
BJU Int
.
2009
;
104
(
10
):
1467
70
. .
20.
Manso
M
,
Pacheco-Figueiredo
L
,
Santos-Silva
A
,
Silva
J
,
Silva
C
,
Cruz
F
.
Renal cell carcinoma with venous thrombus: should surgery be offered when metastasis is present at diagnosis?
Urol Int
.
2018
;
101
(
4
):
387
90
. .
21.
Zhang
Q
,
Ma
R
,
Liu
Z
,
Zhang
S
,
Ma
L
.
A contemporary high-volume center analysis of postoperative complications following surgical management of renal cell carcinoma with tumor thrombus
.
Urol Int
.
2019
;
102
(
4
):
427
34
.
22.
Yu
KJ
,
Keskin
SK
,
Meissner
MA
,
Petros
FG
,
Wang
X
,
Borregales
LD
, et al.
Renal cell carcinoma and pathologic nodal disease: implications for American Joint Committee on Cancer staging
.
Cancer
.
2018
;
124
(
20
):
4023
31
. .
23.
Kroeger
N
,
Pantuck
AJ
,
Wells
JC
,
Lawrence
N
,
Broom
R
,
Kim
JJ
, et al.
Characterizing the impact of lymph node metastases on the survival outcome for metastatic renal cell carcinoma patients treated with targeted therapies
.
Eur Urol
.
2015
;
68
(
3
):
506
15
. .
24.
Liao
X
,
Qiu
S
,
Zheng
X
,
Ai
J
,
Jin
X
,
Gong
L
, et al.
Lymph node density as an independent prognostic factor in node-positive renal-cell carcinoma: results from the surveillance, epidemiology, and end results program
.
Clin Genitourin Cancer
.
2019
;
17
(
5
):
e968
80
. .
25.
Chipollini
J
,
Abel
EJ
,
Peyton
CC
,
Boulware
DC
,
Karam
JA
,
Margulis
V
, et al.
Pathologic predictors of survival during lymph node dissection for metastatic renal-cell carcinoma: results from a multicenter collaboration
.
Clin Genitourin Cancer
.
2018
;
16
(
2
):
e443
50
. .
26.
Blute
ML
,
Leibovich
BC
,
Cheville
JC
,
Lohse
CM
,
Zincke
H
.
A protocol for performing extended lymph node dissection using primary tumor pathological features for patients treated with radical nephrectomy for clear cell renal cell carcinoma
.
J Urol
.
2004
;
172
(
2
):
465
9
. .
27.
Capitanio
U
,
Abdollah
F
,
Matloob
R
,
Suardi
N
,
Castiglione
F
,
Di Trapani
E
, et al.
When to perform lymph node dissection in patients with renal cell carcinoma: a novel approach to the preoperative assessment of risk of lymph node invasion at surgery and of lymph node progression during follow-up
.
BJU Int
.
2013
;
112
(
2
):
E59
66
. .
28.
Babaian
KN
,
Kim
DY
,
Kenney
PA
,
Wood
CG
 Jr
,
Wong
J
,
Sanchez
C
, et al.
Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection
.
J Urol
.
2015
;
193
(
4
):
1101
7
. .
29.
Gershman
B
,
Takahashi
N
,
Moreira
DM
,
Thompson
RH
,
Boorjian
SA
,
Lohse
CM
, et al.
Radiographic size of retroperitoneal lymph nodes predicts pathological nodal involvement for patients with renal cell carcinoma: development of a risk prediction model
.
BJU Int
.
2016
;
118
(
5
):
742
9
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.