Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: a systematic review with meta-analysis

Abstract

Background: Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. Methods:We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias.Results: Five studies published between 2010 and 2014 were eligible for this systematic review with metaanalysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports.Conclusions: LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC. Multiple investigators have demonstrated the heterogeneity in survival of patients with pN0 resections, suggesting the possibility that a significant proportion of these patients are understated, probably because LN metastasis is missed (5-8). However, the survival of patients with pathologic N1 is also heterogenous, ranging from a 5-year survival of 54% to 34% in the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project database (4). The reported risk of recurrence for patients with pathologic Stage IIA-IIB disease ranges from 7% to 55% (9). Keywords: Lymph node ratio (LNR);These results suggest a need to identify patterns of LN involvement that more accurately predict survival, particularly of patients with N1 disease (10,11). Because the thoroughness of nodal examination interacts with the likelihood of detecting nodal metastasis, the number of positive LNs may depend on by the number of LNs examined from the resection specimen. Therefore, the prognostic accuracy of the actual number of positive LNs is potentially restricted (12). The lymph node ratio (LNR)-the number of positive LNs divided by the number of LNs examined-has been suggested to be a more accurate prognostic indicator than the number of LNs with metastasis in different types of cancer including thyroid, gastric, colorectal, and cancer (13)(14)(15)(16)(17)(18)(19).The prognostic value of the LNR in N1 NSCLC remains controversial. We conducted a meta-analysis of published reports in order to evaluate the LNR as a predictor of survival and recurrence in patients with pathological N1 NSCLC. Methods Search strategyW...

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