Survival Benefits Based on the Number of Lymph Nodes Removed during Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis

The role of lymph node dissection (LND) is still controversial for upper tract urothelial carcinoma (UTUC), and there are no guidelines regarding its use. This study was conducted to find a higher level of evidence for the survival benefits based on the number of LNs removed during radical nephroureterectomy (RNUx) through a systematic review and meta-analysis. We included studies comparing patients who underwent LND during RNUx for UTUC. We searched the major electronic databases (Pubmed, Embase(R), and Scopus(R)) and conducted manual searches of the electronically available abstracts of the major international urology cancer meetings [American Society of Clinical Oncology (ASCO), American Urological Association (AUA), and Eropean Association of Urology (EAU)] prior to April 2019 using grouped terms of nephroureterectomy (nephroureterectom*) and lymph node excision (lymphadenectomy; lymph + node*; lymph* + metasta*) with variations in the terms. Study selection, data collection, and risk of bias assessment were performed by two independent authors (A and B). Six retrospective case-control studies included a total of 33,944 patients who underwent RNUx for UTUC, 5071 of whom underwent LND and were finally included in the meta-analysis. The pooled hazard ratio (HR) in these studies revealed that an increased number of LNs removed during RNUx was associated with improved cancer-specific survival (CSS) in patients with UTUC (HR = 0.95, 95% CI: 0.91-0.99;p= 0.07). In addition, increased numbers of LNs removed were associated with improved overall survival (OS) in pN0 patients. However, in pN+ patients, the number of LNs removed showed no survival benefit on CSS, overall survival (OS), or progression-free survival (PFS). Higher numbers of LNs removed during RNUx were associated with improved survival outcomes in patients with UTUC. This study confirmed that LND also has oncological benefits in UTUC patients. Although still a controversial topic, meticulous LND must be considered, and efforts should be made to eliminate as many LNs as possible when administering RNUx for UTUC, especially in patients without clear evidence of LN metastasis.