Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis

Introduction The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients' prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE-). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for potential confounders. Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE-). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95 % CI: 1.43-2.03, I (2) = 66 %; HR = 2.14; 95 % CI: 1.66-2.75, I (2) = 0 %), cancer-specific mortality (RR = 1.59; 95 % CI: 1.42-1.79; HR = 1.52; 95 % CI: 1.19-1.96), and disease recurrence (RR = 3.43, 95 % CI: 1.80-6.54, I (2) = 0 %). Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report.