The role of lymph node dissection in the management of renal cell carcinoma: a systematic review and meta‐analysis

Abstract

Our objective was to evaluate the role of retroperitoneal lymph node dissection (LND) in non-metastatic (M0) and metastatic (M1) renal cell carcinoma (RCC). We searched Medline, EMBASE, Web of Science and Scopus from database inception to 29 August 2017 for studies of patients who underwent partial or radical nephrectomy for M0 or M1 RCC. Two investigators independently selected studies for inclusion. Risk of bias was assessed using the Newcastle-Ottawa scale, Cochrane Collaboration tool and National Heart, Lung and Blood Institute Quality Assessment Tool. Random effects meta-analysis was performed for all-cause-mortality. The GRADE approach was used to characterize quality of evidence. A total of 51 unique studies were included in the qualitative systematic review. Risk of bias was low in 41/51 (80%) studies. LND was not associated with all-cause mortality in either M0 (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.92-1.12; I = 0%; four studies), M1 (HR 1.04, 95% CI 0.83-1.29; I = 0%; two studies), or pooled M0 and M1 settings (HR 1.00, 95% CI 0.92-1.09; I = 0%; seven studies), with no statistically significant differences according to M stage subgroups (P = 0.50). In the three studies that examined M0 subgroups with a high risk of nodal metastasis, LND was not associated with improved oncological outcomes. Studies on the association of extent of LND with survival reported inconsistent results. Meanwhile, a small proportion of patients with pN1M0 disease demonstrate durable long-term oncological control after surgery, with 10-year cancer-specific survival of 21-31%. Nodal involvement is independently associated with adverse prognosis in both M0 and M1 settings. GRADE quality of evidence was moderate or low for the outcomes examined. Although LND yields independent prognostic information, the existing literature does not support a therapeutic benefit to LND in either M0 or M1 RCC. High-risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long-term survival after surgical resection.

Beyond the predictors of lymph node metastases in patients undergoing lymph node dissection for renal cell carcinoma: the impact of tumour side and location

“…Intriguingly, despite patients with tumours involving multiple kidney locations appeared to have higher rates of nodal metastases in the analyses stratified by tumour side, tumor location was not associated with LNI or NP at final multivariable analysis (12). Moreover, as previously reported (1)(2)(3)6), the strongest predictors of nodal metastases at surgery were tumour size, stage and grade along with radiographic lymphadenopathy (cN1) and cM1 disease (3,11,13).…”

“…These conflicting recommendations reflect the current controversial evidence on the indications, extent and prognostic impact of LND for RCC (3)(4)(5)(6). Furthermore, they might partly explain the trend towards lower rates of LND over the last decades, with LND rates stabilizing after 2010 in both Europe and US (7,8).…”

“…Indeed, as urologic surgeons, we ultimately have to balance the potential benefits and harms of LND in the individual patient. In this regard, while LND is not associated with an increased risk of perioperative morbidity in experienced hands (3,5,10), preoperative identification of patients with nodal metastases is a key unmet need.…”

“…Several nomograms, risk scores and multivariable regression models have been proposed to identify patients at higher risk of lymph node invasion (LNI) (3,6). Although these tools are still suboptimal to guide decision-making, interestingly the most common covariates associated with pN+ disease are tumour size, stage and grade along with radiographic lymphadenopathy (cN1) (3).…”

A Festschrift in Honor of Edward M. Messing, MD, FACS

“…Lymph node (LN) involvement in renal cell carcinoma (RCC) is typically associated with a poor prognosis [ 56 ]. While LND may provide diagnostic information in RCC, the therapeutic benefit remains controversial [ 57–61 ]. Several studies have suggested that LND does not confer a survival advantage in RCC patients, even in high-risk patients or those with clinical lymphadenopathy [ 58, 60, 61 ].…”