Radical Nephrectomy With or Without Lymph Node Dissection for High-Risk Nonmetastatic Renal Cell Carcinoma
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersPURPOSE
LND may benefit patients at increased risk of lymph node (LN) metastases from renal cell carcinoma (RCC). We therefore evaluated the association of LND with survival among high-risk patients undergoing radical nephrectomy (RN) for RCC.
MATERIALS AND METHODS
We identified 2,722 patients with M0 RCC who underwent RN with or without LND at two international centers from 1990-2010. The associations of LND with development of distant metastases, cancer-specific mortality (CSM), and all-cause mortality (ACM) were evaluated using propensity score techniques and traditional multivariable Cox regression. Subset analyses examined patients at increased risk of LN metastases.
RESULTS
Overall, 171 (6.3%) patients were pN1. Median follow-up was 9.6 years. Clinicopathologic features were well balanced after PS adjustment. LND was not significantly associated with a reduced risk of distant metastases, CSM, or ACM in the overall cohort, among patients with preoperative radiographic lymphadenopathy (cN1), or across increasing probability of pN1 disease from ≥0.10 to ≥0.50. Neither performance of extended LND nor the extent of LND was associated with improved oncologic outcomes.
CONCLUSIONS
The current analysis of a large, international cohort indicates that LND is not associated with improved oncologic outcomes among high-risk patients undergoing RN for M0 RCC, including those with radiographic lymphadenopathy (cN1) or across increasing probability thresholds for pN1 disease.
Additional Info
Radical Nephrectomy With or Without Lymph Node Dissection for High-Risk Non-Metastatic Renal Cell Carcinoma: A Multi-Institutional Analysis
J Urol 2017 Dec 07;[EPub Ahead of Print], B Gershman, RH Thompson, SA Boorjian, A Larcher, U Capitanio, F Montorsi, C Carenzi, R Bertini, A Briganti, CM Lohse, JC Cheville, BC LeibovichFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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The authors are to be congratulated for performing an extensive analysis in the largest series of patients (N = 2657) reported on the impact of lymph node dissection (n = 1183; 45%) on oncological outcomes after radical nephrectomy (RN) for nonmetastatic disease. This is essentially an international, multi-institutional validation study of previously reported Mayo Clinic results that failed to identify a positive survival outcome with lymph node dissection (LND) at the time of RN.1 The authors applied high-level propensity score techniques to compare cohorts; however, 157 patients who had LND were not included because of inappropriate matching. Therefore, propensity score matching may in and of itself introduce imbalance, and so a properly performed randomized controlled trial remains the gold standard analysis.2
The current analysis supports a recently reported secondary analysis of the ASSURE trial, which also failed to reveal a positive impact of LND on overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) in the adjuvant setting.3 It is clear that having positive lymph nodes is the single most important independent predictor of survival in all of these categories, regardless of T stage in surgically resected disease.4 Patients with high-risk primaries have a 33% to 50% risk of positive regional nodes.5
The impetus for LND comes from traditional RN technique and metastasectomy experience wherein patients presenting with isolated retroperitoneal or fossa recurrences due to lymphadenopathy were resected and achieved extended survival.6,7,8 In addition, it was also determined in the cytokine era that those patients who underwent debulking retroperitoneal LND in the face of N1-2 disease experienced improved survival.9 Notwithstanding the negative results of EORTC-30881, the morbidity of LND at the time of RN is extremely low.10 Therefore, the driving force behind performing LND at the time of RN is to identify those patients most likely to benefit as salvage metastasectomies or debulking surgeries are associated with increased morbidity.
Recently, effort has been directed to stratify patients at highest risk of positive nodes at the time of RN at centers that specialize in surgical management of advanced RCC.5 A few key issues dominate in this regard. First of all, the LND reported in the current analysis was done in an ad hoc or surgeon-discretion manner. Protocol or algorithms to define those patients at highest risk of harboring lymph nodes were not standardized and rarely employed. Second, surgical templates for LND have not been adhered to; as in the current study, the median number of nodes removed was six and in the ASSURE trial, only three. Fewer than 10% of patients had 13 or more lymph nodes resected, indicating an adequate LND at the time of RN. It has been determined that at least 15 nodes need to be removed to achieve 90% probability of detecting lymph node invasion.11 When LNs are positive, an extended dissection and increased LN yield is associated with improved survival.12,13 Five-year survivors of high-risk advanced kidney cancer are becoming increasingly common.14
The randomized, double-blind, phase III S-TRAC trial randomized 615 patients with high-risk clear cell cancer to receive adjuvant sunitinib or placebo. DFS in the sunitinib arm was superior (median DFS, 6.8 years) to that in the placebo arm (median, 5.6 years).15 Results of the S-TRAC trial came as a surprise because of the negative results of the ASSURE trial. What is clear in these randomized trials is that the surgical technique is not well-defined in terms of protocols for performing LND in the face of high-risk disease and in defining surgical templates. Will under-staged patients be undertreated? Will control of the retroperitoneum become more important as DFS improves with individualized targeted therapy, sequential therapy, new drugs, and checkpoint inhibitor therapy? Urologic oncologists can do more to add quality control to surgical technique for future drug trials of first- and second-line treatments in high-risk disease.
The current analysis adds to, but does not settle, the debate regarding the value of LND in high-risk renal cell cancer; however, clearly more prospective studies performed to determine the place of LND in managing high-risk and advanced renal cell cancer are needed. Standardized surgical templates for node dissection must be utilized to improve the quality of surgery performed in pivotal drug trials for high-risk patients.
References