ORIGINAL ARTICLE

Impact of lymphadenectomy in management of renal

cell carcinoma

Ashraf Hamid Ibrahim *, Abd ElHamid H. Ezzat 1

Department of Surgical Oncology, National Cancer Institute – Cairo University, Egypt

Received 23 May 2011; accepted 24 January 2012

Available online 14 March 2012

KEYWORDS

Radical nephrectomy;

Lymphadenectomy

Abstract Purpose: To evaluate the impact of regional lymphadenectomy as part of a management

plan on morbidity, morbidity and survival in renal cell carcinoma (RCC).

Patients and methods: A retrospective study reviewing 158 cases diagnosed as RCC at the National

Cancer Institute, Cairo university, Egypt, during the time period from 2000 to 2007. Histopathol-

ogical data and significant operative and postoperative events were retrieved to compare three lym-

phadenectomy groups; Group A, where more than 5 nodes were dissected, Group B where 5 or less

nodes were dissected and Group C where no nodal dissection was done.

Results: More positive lymph nodes were seen in group A (37.8%) compared to group B (9.6%)

(p= 0.002). Lymph node positivity was significantly associated with higher grade (p= 0.005),

but not with larger tumor size (p= 0.221). There was no significant difference in overall survival

between the three lymphadenectomy groups (p= 0.163). Overall survival was not significantly

affected by lymph node status (p= 0.585).

Conclusion: Regional lymphadenectomy in RCC has no impact on the mortality or morbidity.ª 2012 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V.

All rights reserved.

Introduction

Renal Cell Carcinoma (RCC) accounts for approximately 3%of adult malignancies. It is generally accepted that RCC usu-

ally metastasizes to distant organs through blood circulationrather than lymphatogenous dissemination. Clinical and au-

topsy studies have revealed that most lymph node [LN] metas-tases accompany distant metastases [1]. Positive LNs werefrequently accompanied with advanced stage and poor prog-

nosis, which suggested the diagnostic and prognostic signifi-cance of lymphadenectomy (LND) [2]. The role of lymphnode dissection (LND) in renal cell carcinoma (RCC) remains

controversial [3].Although LND in patients with low-risk disease had no ben-

efit in a randomized clinical trial; LND in patients with high-risk

disease improved stage assessment and might prolong survival[4–6]. The indications for and extent of LND in patients with ad-vanced RCC could be based on clinical and/or pathologic fac-

1110-0362 ª 2012 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

http://dx.doi.org/10.1016/j.jnci.2012.02.001

* Corresponding author. Tel.: +20 01001402770.

E-mail addresses: yjashraf71@hotmail.com (A.H. Ibrahim), hamidez

zat@hotmail.com (A.E.H. Ezzat).1 Tel.: +20 01005214033.

Peer review under responsibility of the National Cancer Institute,

Cairo University.

Production and hosting by Elsevier

Journal of the Egyptian National Cancer Institute (2012) 24, 57–61

Cairo University

Journal of the Egyptian National Cancer Institute

www.nci.cu.adu.egwww.sciencedirect.com

tors [7]. Several investigators attempted to select patients forLND during radical nephrectomy based on predictors of regio-nal lymph node involvement [8,9].

Patients and methods

This was a retrospective study reviewing cases diagnosed as re-

nal cell carcinoma (RCC) who presented to the National Can-cer Institute (NCI), Cairo University, Egypt, during the timeperiod 2000 to 2007. All patients were treated with radical

nephrectomy. All patients had a pre-operative routine labora-tory work-up, pelvi-abdominal ultrasound and/or abdominalCT. Patients presented with metastatic disease were excluded

from this study.Full histopathological data were obtained for each patient

including tumor site and size, pathological type and grade,peri-nephric fat infiltration, venous involvement and status

of lymph nodes.Patients were classified into 3 main groups based on the

number of lymph nodes dissected according to their pathology

report; group A (n= 37) included patients with >5 lymphnodes in the pathology report, group B (n = 52) includingpatients with 65 lymph nodes and group C (n= 69) including

those with no lymph nodes in the pathology report. Patientswere followed up till 2010 by clinical examination, ultrasoundand computerized tomography (CT scan).

Statistical methods

Data were analyzed using SPSS win statistical package version

15 (SPSS Inc., Chicago, IL). Chi-square test was used to exam-ine the relation between qualitative variables. Survival analysiswas done using Kaplan–Meier method and a comparison be-

tween two survival curves was done using log-rank test. A pvalue <0.05 was considered significant.

Results

Patients’ mean age at presentation was 53.7 years ± 14.2;

46.8% were in the age group of 41–60 years. There was a slightfemale predominance (male to female ratio, 0.93). The mainpresenting symptom was loin pain (n = 116) followed byhematuria (n= 27) and abdominal mass (n = 13).

Renal capsular and perinephric fat infiltration were mani-fested in 51% of cases and 11% showed hilar vascular inva-sion. Clear cell carcinoma was the main pathological type

(47%) followed by granular cell carcinoma (20%) and mixedcell tumors (18%). Nearly 73% of cases had grade 2 tumorswhile 13% had grade 1 and 14% had grade 3. Tumor sizewas >7 cm in 74.7% of cases.

Positive lymph nodes were seen in 14/37 cases (37.8%) ingroup A and 5/52 cases (9.6%) in group B (p= 0.002). Therelation between lymph node positivity and tumor size and

grade is shown in Table 1. Grade 3 tumors had significantlyhigher frequency of positive nodes (54%) compared to grades1 and 2 (16%).

Post-operative period was uneventful in the majority ofcases (92.4%). Four cases (2.5%) died due to pulmonaryembolism and 8 patients (5.1%) had complications in the formof postoperative hemorrhage, diaphragmatic injury and infe-

rior vena cava (IVC) thrombosis. Overall survival was 65%as shown in Table 2. Loco-regional recurrences as well asmetastasis were reported in 26 patients (16.5%).

There was no significant difference in overall survival be-tween the three lymphadenectomy groups (Fig. 1). Fig. 2shows that the overall survival was not significantly affected

by lymph node status (p= 0.585).

Discussion

RCC is primarily a disease of the elderly patients, with typicalpresentation in the sixth and seventh decades of life, with a

male-to-female predominance of 3:2 [10,11]. While Kwon

Table 1 Lymph node status in relation to tumor size and grade in groups A and B (n = 89) patients with RCC.

LN negative (n= 70) LN positive (n = 19) Total (%) p value

Tumor size

67 cm 18 (90.0%) 2 (10.0%) 20 (100.0%) 0.221*

>7 cm 52 (75.4%) 17 (24.6%) 69 (100.0%)

Grade

1 & 2 64 (84.2%) 12 (15.8%) 76 (100.0%) 0.005**

3 6 (46.2%) 7 (53.8%) 13 (100.0%)

RCC: renal cell carcinoma; LN: lymph node.

p 6 0.05.* p value not significant.

** p value significant.

Table 2 Cumulative overall survival at 12 months of follow

up for all patients and in separate groups and in relation to

lymph node status.

n Cumulative overall

survival (%)

p value

All patients 158 65.0

Study groups

Group A 37 73.3

Group B 52 68.0

Group C 69 59.0 0.163*

Lymph nodes

+ve 19 70.4 0.585**

�ve 70 69.8

p 6 0.05.* p value not significant.

** p value not significant.

58 A.H. Ibrahim, A.E.H. Ezzat

et al. found that the mean age was 52.6 years [12], in this study,the peak age of presentation in the majority of patients was inthe age group of 40–60 years with slight female predominance

(1.1:1.0). All the cases in this study were symptomatic on pre-sentation mostly with loin pain. CT and ultrasound studiesconfirmed the diagnosis.

One unique feature of RCC is its predilection for involve-

ment of the venous system, which is found in 10% of RCCs,more often than in any other tumor type [13]. In this study ve-nous involvement was documented in 17 cases (11%). Peri-

nephric fat infiltration by the tumors was found in 80 cases(51%).

In the present study, conventional RCC represented about

85% of the cases; this was in agreement with studies statingthat conventional RCC accounts for approximately 70–80%and 87.7% of all cases [12–14].

In this study the number of documented cases of positivelymph nodes were 19 out of 89 cases in groups A and B(24.3%). This agreed with a study reporting a rate of lymphnode affection in RCC of about 21% [16]. However, another

study, and due to modern technique and early screening op-tions, found only 37 out of 1503 patients with positive lymphnodes [12].

The study published in 2011 stated that patients with LNmetastasis (pN 1) had larger tumors and greater pathologicT stage and grade than did the patients with stage pNx or

pN0. Patients with negative LN metastasis (pN0) had largertumors and greater pathologic T stage and grade than patientswith stage p0x. Of the 763 patients who underwent LND, 560(73.4%) had a clinically suspicious LN mass (LN enlargement

1 cm or contrast enhance- mint) on preoperative computedtomography, and LND revealed 37 (6.6%) with metastases.

Of the other 203 patients who underwent LND without suspi-cion of nodal enlargement (cN0), none had pathologically LN-positive disease [12].

Positive lymph nodes in the current study were found in24.6% of cases with tumors >7 cm compared to 10% of smal-ler tumors, however, the difference was not statistically signif-icant. It was previously documented that the rate of lymph

node affection was stage dependent [16]. On the other hand,higher tumor grade was significantly associated with higherfrequency of positive nodes (p= 0.005). This agreed with pre-

vious studies [12,16,17].The rate of positive lymph nodes was higher if more than 13

nodes were dissected (extended lymphadenectomy), with 21%

positive nodes in patients with greater than or equal to 13nodes dissected and 10% positive for patients with fewer than13 nodes in the specimen [16]. In this study higher number of

positive lymph nodes were found when more nodes were dis-sected; i.e., 14/37 cases (37.8%) in group A versus 5/52 cases(9.6%) in group B (p = 0.002).

In this study operative mortality was 2.5%, almost all died

due to pulmonary embolism, while hemorrhage, diaphragmaticinjury and IVC thrombosis were encountered in 5.1% of cases.

Disease recurred in (13.4%), of which 17.3% with local

recurrence and 82% with distant metastases. The most fre-quent site of local recurrence was the regional LNs, and themost frequent distant metastatic site was the lungs [12]. LN

metastasis was a significant prognostic factor for 5-year sur-vival but not in patients with stage N1and N2. On univariateanalysis, patients with pN0 tumors were significantly morelikely to have distant metastasis and to die than were those

with pNx tumors. After adjusting for tumor stage and nucleargrade, the differences in 5-year survival were statistically signif-

0 12 24 36 48 60 72 84 96 108 120Time (months)

0.0

0.2

0.4

0.6

0.8

1.0

Cum

Sur

viva

l Pro

port

ion

GroupGroup AGroup BGroup C

Group A-censoredGroup B-censoredGroup C-censored

Overall Survival

p = 0.163

Figure 1 Cumulative overall survival at 12 months of groups A, B and C of RCC patients studied.

Impact of lymphadenectomy in management of renal cell carcinoma 59

icant for patients with stage pNx and pN0 tumors (p = 0.008).The survival rate did not vary according to the LN location,even when grouping patients according to hilar and other loca-

tions. It was observed that the differences in the survival ratewere relative to the LN metastasis size. Accordingly, patientswith LN metastases 3 cm or less had significantly better 5-yeardistant metastasis-free survival (p= 0.003) [12]. Generally,

overall operative mortality after radical nephrectomy was re-ported to be around 1% [16,17].

Metastasis and progression in RCC occurred in one third of

the patients [16] and about (13.4%) [12] of the patients who pre-sented with localized disease. In this study there were only 26cases (16.46%) with documented progression of the disease in

the formofmetastasis and/or local recurrence of the tumor, withthe percentage of distant metastases in relation to the patholog-ical T stage showing increased percentage according to T stage

as 13%, 16% and 17% for T1, T2 and T3, respectively.The relation between LN status and progression of the

RCC disease showed that 25% of cases with positive lymphnode affection developed progression in comparison to 13%

of cases with negative lymph nodes [17].It was reported that there was a significant survival advantage

in patientswhowere treatedwith extended lymphadenectomywith

the radical nephrectomy. It was concluded that radical nephrec-tomy plus extended lymphadenectomy benefited at least 4% ofall patients [17]. In this study only prognostic value of lymphade-

nectomywas demonstrated while therapeutic value was not signif-icantly represented. The difference in overall survival rates was notstatistically significant when comparing positive to negative lymph

node status groups (p= 0.163) as there was no significant differ-ence in overall survival between the three lymphadenectomy

groups. So the value of lymphadenectomy in RCCwas only prog-nostic for stage determination but not of significant therapeutic va-lue. Similarly, overall survival was not significantly affected by

lymph node status (p = 0.585).We could conclude that, regional lymphadenectomy in

RCC had no statistically significant impact on the mortalityor morbidity.

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0.0 20.0 40.0 60.0 80.0 100.0 120.0Time (months)

0.0

0.2

0.4

0.6

0.8

1.0

Cum

Sur

viva

l Fun

ctio

n

LN+ve-ve+ve-censored-ve-censored

Overall Survival

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60 A.H. Ibrahim, A.E.H. Ezzat

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incidentally detected tumors. J Urol 2000;163:426–30.

Impact of lymphadenectomy in management of renal cell carcinoma 61