Seminars article
Role of lymph node dissection in renal cell cancer

https://doi.org/10.1016/j.urolonc.2018.03.006Get rights and content

Highlights

  • LND is the most reliable way to stage the retroperitoneum in RCC.

  • The only randomized trial looking at the role of LND in RCC failed to show improvement in survival in low risk disease.

  • Even though isolated lymph node involvement portends poor prognosis, a small subset may experience prolonged oncological control following LND.

  • Evidence supporting LND in high risk cases (≥T3, size >10 cm, sarcomatoid features) is weak and needs validation in prospective trials employing pre-specified template based LND.

Abstract

Lymph node metastasis in renal cell cancer (RCC) portends an extremely poor prognosis. Despite proven staging benefit, the therapeutic value of lymph node dissection in RCC remains questionable. The only prospective randomized trial examining its role failed to show any benefit. However, subsequent retrospective publications have attempted to identify high-risk cohorts and clinical scenarios where removal of nodes may improve survival. The aim of this article is to provide a comprehensive review looking at the role of lymph node dissection in RCC if any, the ideal extent of dissection, and also tools a clinician could employ to identify those who would most likely benefit from this exercise.

Introduction

“Radical Nephrectomy” as described by Robson entailed removal of the lymphatic drainage field along with the disease bearing kidney as one of the important requirements for achieving cure [1]. Five decades later, despite proven staging benefit, the therapeutic benefit of lymph node dissection (LND) in renal cell carcinoma (RCC) remains questionable. The only prospective randomized controlled trial to date showed that complete lymph node removal from the crus of the diaphragm to the bifurcation of the aorta/vena cava failed to confer any survival benefit in “low risk” RCC [2]. Increased detection of small, indolent tumors; proliferation of minimally invasive nephron sparing surgery [3], and lack of perception of benefit has resulted in fewer urologists performing LND over the past decade [4].

However, some retrospective series claim that certain “high risk” groups may benefit from LND [5], [6], [7], [8], [9], [10]. Hence, the aim of this review is to ascertain the role of LND in the management of RCC if any, and whether development of novel imaging, molecular and genomic tools have contributed to the identification of those who might benefit from LND.

Section snippets

Patterns of lymphatic spread in RCC

Since literature is still unclear regarding the role of LND in RCC, it makes sense to revisit the patterns of lymphatic drainage of the kidney and understand the reason why spread of RCC is so unpredictable. Detailed injection studies in cadavers carried out in the early half of the last century contributed to this knowledge [11] and helped in constructing the anatomic lymphatic drainage maps of the kidneys [12].

From the right kidney, efferent lymphatic vessels running anterior to the renal

Staging benefit of LND

Knowing the complexity of lymphatic drainage of the kidney, it would be ideal if intraoperative assessment or imaging was accurate for assessing the extent of lymph node involvement. Unfortunately, in the EORTC 30881 trial, less than 20% of the palpably enlarged nodes during surgery were positive on histopathological examination [2]. Both CT and MRI are inadequate in detecting metastasis in nodes of normal shape and size [5]. Hence, LND is currently the only reliable way to stage accurately [3].

Therapeutic benefit of LND

Although the role of LND in staging is well established, its role in improving oncological outcomes is debatable. Table 1 highlights some of the prominent publications focused on this issue. The only prospective, randomized phase III trial (EORTC 30881) which attempted to solve this controversy failed to show any survival benefit in clinically node negative patients [2]. However, these results could not be generalized due to various issues. The 4% incidence of lymph node involvement in the

Extent of LND

A retrospective study looking at the extent of lymphadenectomy showed that systematic, extended LND in cT1–4 RCC was associated with better survival compared to just sampling or lack of LND [27]. Crispen et al. suggested templates for LND based on his study on high-risk patients [8]. However, a major limitation was lack of standardized dissection during the study period. Whitson et al. showed that an increase of 10 lymph nodes in a patient with 1 positive lymph node was associated with a 10%

LND for nodal recurrence

Isolated lymph node recurrence following nephrectomy is rare [5] and salvage LND is challenging and worth the effort only if it improves outcome. In a study done in the pretargeted therapy era, a series from Mayo showed a median CSS of 33.3 months following salvage LND [34]. A retrospective multi-institutional study of 22 patients in this setting seemed to show durable PFS irrespective of histology or original clinical stage [35]. However, most of this cohort had not undergone LND at the time

Complications of LND

Complications associated with LND include injury to major vessels/bleeding, bowel injury/damage to adjacent organs, lymphocele, and chylous ascites [2], [37]. However, the EORTC trial failed to show any significant difference in complication rates between the extended LND and no LND arms (26% vs. 22%) [2]. A systematic review of LND in locally advanced RCC too failed to show any difference in adverse events in the LND vs. no LND groups [23]. With the proliferation of minimally invasive surgery,

Imaging

CT and MRI are ideal tools to diagnose and stage RCC but fall short of accurately predicting lymph node involvement, more so for detecting micrometastasis in normal-sized nodes [39], [40]. Association between lymph node size and metastatic involvement was reported to be around 32%–43% even in lymph nodes>1 cm in size [41], [42]. A more recent publication has shown that the sensitivity, specificity, and positive and negative predictive values for preoperative CT were 82%, 71%, 56%, and 90%,

Conclusion

LND continues to be the most reliable way to stage the retroperitoneum in RCC. Extended dissection and removal of at least 15 nodes improves accuracy. The only randomized trial looking at the role of LND in RCC failed to show improvement in survival in low-risk disease. Evidence supporting LND in high-risk cases (≥T3, size > 10 cm, sarcomatoid features, etc.) and for isolated nodal recurrence is weak and needs validation. Well-designed, multi-institutional, prospective, randomized trials using a

References (54)

  • N. Kroeger 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)
  • H.J. Bekema et al.

    Systematic review of adrenalectomy and lymph node dissection in locally advanced renal cell carcinoma

    Eur Urol

    (2013)
  • B. Gershman et al.

    Radical nephrectomy with or without lymph node dissection for nonmetastatic renal cell carcinoma: a propensity score-based analysis

    Eur Urol

    (2017)
  • A. Herrlinger et al.

    What are the benefits of extended dissection of the regional renal lymph nodes in the therapy of renal cell carcinoma

    J Urol

    (1991)
  • B.T. Ristau et al.

    Retroperitoneal lymphadenectomy for high risk, nonmetastatic renal cell carcinoma: an analysis of the ASSURE (ECOG-ACRIN 2805) Adjuvant Trial

    J Urol

    (2018)
  • B. Gershman 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)
  • B. Gershman et al.

    Lymph node dissection is not associated with improved survival among patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma: a propensity score based analysis

    J Urol

    (2017)
  • S.A. Boorjian et al.

    Surgical resection of isolated retroperitoneal lymph node recurrence of renal cell carcinoma following nephrectomy

    J Urol

    (2008)
  • C.M. Russell et al.

    Surgical outcomes in the management of isolated nodal recurrences: a multicenter, international retrospective cohort

    J Urol

    (2014)
  • R.G. Ferrigni et al.

    Chylous ascites complicating genitourinary oncological surgery

    J Urol

    (1985)
  • T.N. Chapman et al.

    Laparoscopic lymph node dissection in clinically node-negative patients undergoing laparoscopic nephrectomy for renal carcinoma

    Urology

    (2008)
  • X. Ming et al.

    Value of frozen section analysis of enlarged lymph nodes during radical nephrectomy for renal cell carcinoma

    Urology

    (2009)
  • U.E. Studer et al.

    Enlargement of regional lymph nodes in renal cell carcinoma is often not due to metastases

    J Urol

    (1990)
  • A.R. Guimaraes et al.

    Pilot study evaluating use of lymphotrophic nanoparticle-enhanced magnetic resonance imaging for assessing lymph nodes in renal cell cancer

    Urology

    (2008)
  • K.N. Babaian et al.

    Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection

    J Urol

    (2015)
  • N. Kroeger et al.

    Clinical, molecular, and genetic correlates of lymphatic spread in clear cell renal cell carcinoma

    Eur Urol

    (2012)
  • A. Soultati et al.

    Identifying the metastatic subclone by exhaustive sampling of primary and metastasis in clear cell renal cell carcinoma (ccRCC) pair

    Eur Urol Suppl

    (2016)
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