Urologic Oncology: Seminars and Original Investigations
Seminars articleRole of lymph node dissection in renal cell cancer
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
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