Radical Nephrectomy With or Without Lymph Node Dissection for Nonmetastatic Renal Cell Carcinoma: A Propensity Score-based Analysis: Beyond the Abstract

Lymph node dissection (LND) for renal cell carcinoma (RCC) dates back to Robson’s original description of radical nephrectomy in 1969[1].  Indeed, Robson and colleagues suggested a therapeutic benefit to LND, attributing, in part, the improved survival in their series compared to contemporaneous studies to “removal of the lymphatic drainage system,” which was involved by RCC in in 22.7% of patients. 

However, RCC has historically been characterized by a predominantly hematogenous route of spread[2], and the oncologic benefit of LND in the management of RCC has remained unproven.  While several retrospective studies provided evidence to support a therapeutic benefit to LND[3-5], the only randomized trial to examine this issue, EORTC 30881, reported no difference in survival with performance of LND[6].  Still, EORTC had a low incidence of lymph node metastases – only 4% – and since removal of benign lymph nodes cannot be expected to impact survival, advocates of LND have argued that LND may still benefit higher-risk patients.

To this end, we conducted a propensity-score based analysis to examine the association of LND with oncologic outcomes among patients undergoing radical nephrectomy (RN) for RCC, specifically focusing on patients at increased risk of lymph node metastases[7].  In short, LND was not associated with improved survival in the overall cohort, nor among high risk patients, including those with radiographic lymphadenopathy (cN1) or across increasing threshold probabilities for lymph node involvement ranging from 0.05 to 0.50.  Moreover, the extent of LND was likewise not associated with oncologic outcomes.  

While our findings support the results of EORTC 30881, they contradict older retrospective studies.  How is one to reconcile these disparate results?  Notwithstanding the inherent potential limitations of observational studies, there is evidence to support the historically hematogenous, rather than lymphogenous, route of dissemination for RCC.  For instance, whereas isolated lymph node metastases in the absence of distant metastases are rare, comprising only 2-5% of non-metastatic cases[2, 8, 9], distant metastases are present in more than half of patients with lymph node involvement[3].  Moreover, anatomic mapping studies have suggested that renal lymphatics may bypass the retroperitoneal lymph nodes, noting direct lymphovenous communications to the renal vein, IVC, and thoracic duct[10].

Ultimately, although it appears that LND does not provide a therapeutic benefit for the majority of patients with RCC, it may still provide valuable staging information.  Specifically, given the frequent co-existence of distant metastases in the setting of lymph node involvement, isolated nodal disease may be an excellent marker for occult systemic disease and risk of postoperative progression.  Although there is, as yet, no established adjuvant therapy for surgically resected non-metastatic RCC, such patients may be candidates for enrollment into clinical trials and more intensive surveillance protocols.

Written by: Boris Gershman1 and Bradley C. Leibovich2

1Divison of Urology, Rhode Island Hospital and The Miriam Hospital, Providence, RI
2Department of Urology, Mayo Clinic, Rochester, MN


References:
1. Robson CJ, Churchill BM, Anderson W. The results of radical nephrectomy for renal cell carcinoma. J Urol. 1969;101(3):297-301.

2. Capitanio U, Becker F, Blute ML, et al. Lymph node dissection in renal cell carcinoma. Eur Urol. 2011;60(6):1212-20.

3. Pantuck AJ, Zisman A, Dorey F, et al. Renal cell carcinoma with retroperitoneal lymph nodes: role of lymph node dissection. J Urol. 2003;169(6):2076-83.

4. Vasselli JR, Yang JC, Linehan WM, White DE, Rosenberg SA, Walther MM. Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma. J Urol. 2001;166(1):68-72.

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. Blom JH, van Poppel H, Marechal JM, 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.

7. Gershman B, Thompson RH, Moreira DM, et al. Radical Nephrectomy With or Without Lymph Node Dissection for Nonmetastatic Renal Cell Carcinoma: A Propensity Score-based Analysis. Eur Urol. 2016.

8. Karakiewicz PI, Trinh QD, Bhojani N, et al. Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease: prognostic indicators of disease-specific survival. Eur Urol. 2007;51(6):1616-24.

9. Delacroix SE, Jr., Chapin BF, Chen JJ, et al. Can a durable disease-free survival be achieved with surgical resection in patients with pathological node positive renal cell carcinoma? J Urol. 2011;186(4):1236-41.

10. Karmali RJ, Suami H, Wood CG, Karam JA. Lymphatic drainage in renal cell carcinoma: back to the basics. BJU international. 2014;114(6):806-17.

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