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Characterizing the Impact of Lymph Node Metastases on the Survival Outcome for Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapies

European Urology, Volume 68, Issue 3, September 2015, Pages 506 - 515



It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients.


To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT).

Design, setting, and participants

Patients (n = 2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype. Additional analyses (n = 1536) were performed in subgroups of patients with supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non–clear cell RCC (nccRCC) patients, respectively.

Outcome measurements and statistical analysis

The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS).

Results and limitations

All patients with LNM had worse PFS (p = 0.001) and OS (p < 0.001) compared to those without LNM. Compared to patients without LNM (PFS 8.8 mo; OS 25.1 mo), any SBD LNM involvement was associated with worse PFS (SBD, 6.8 mo; p = 0.003; SPD+/SBD+, 5.5 mo; p < 0.001) and OS (SBD, 16.2 mo; p < 0.001; SPD+/SBD+, 11.5 mo; p < 0.001). Both SBD and SPD+/SBD+ LNM were retained as independent prognostic factors in multivariate analyses (MVA) for PFS (p = 0.006 and p = 0.022, respectively) and OS (both p < 0.001), while SPD LNM was not an independent risk factor. Likewise, in ccRCC, SBD LNM (19.8 mo) and SPD+/SBD+ LNM (12.85 mo) patients had the worst OS. SPD+/SBD+ LNM (p = 0.006) and SBD LNM (p = 0.028) were independent prognostic factors for OS in MVA, while SPD LNM was not significant (p = 0.301). The study is limited by its retrospective design and the lack of pathologic evaluation of LNM in all cases.


The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT.

Patient summary

The presence of lymph node metastases below the diaphragm is associated with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients.

Take Home Message

Lymph node metastases are associated with adverse prognostic International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk factors and poor prognosis in mRCC patients treated with targeted therapies. The question of whether or not lymph node dissection could improve the outcome for this group of patients may be important in clinical trials.

Keywords: Lymph node metastases, Lymph nodes, Targeted therapies, Treatment response, Survival outcome, Renal cell carcinoma.


a Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada

b Department of Urology, University Medicine, Greifswald, Germany

c Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine at the University of California Los Angeles, CA, USA

d Auckland City Hospital, Auckland, New Zealand, Auckland, New Zealand

e Department of Medical Oncology Johns Hopkins Hospital, Baltimore, MD, USA

f Division of Oncology, Stanford Medical Center, Stanford, CA, USA

g Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada

h Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada

i Department of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada

j Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

k Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA

l Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

m Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada

n Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium

o Department of Oncology, Aarhus University Hospital, Aarhus, Denmark

p Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Corresponding author. University of Calgary, Tom Baker Cancer Center, 1331 29th Street NW, Calgary, AB T2N 4N2, Canada. Tel. +1 403 521 3166; Fax: +1 403 283 1651.