4L lymph node dissection in non-small cell lung cancer: an updated systematic review and subgroup meta-analysis

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with lymph node involvement being a key prognostic factor. Systemic mediastinal lymph node dissection is a standard component of surgical treatment; however, the role of specific nodal stations, such as the left lower paratracheal (4L) lymph nodes, remains controversial. While some studies suggest that 4L lymph node dissection (4LND+) may improve overall survival (OS), others raise concerns about increased complication rates. Current guidelines provide no clear consensus on whether 4LND+ should be performed routinely. Hence, we aimed to evaluate the effects of 4LND+ in patients with left-sided NSCLC on OS and complication rates, with subgroup analyses for stage I NSCLC, left upper lobe (LUL) and left lower lobe (LLL) tumors.

We searched PubMed, Scopus, and Wiley for studies comparing outcomes between patients with NSCLC undergoing or not undergoing 4LND+. The primary endpoint was OS, while secondary endpoints focused on complication rates. Subgroup analyses examined differences in stage I, LUL and LLL tumors. Statistical analysis was performed using Review Manager 5.1.7 (Cochrane Collaboration), and heterogeneity was assessed with I² statistics. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration No. CRD42025642958).

Patients in the 4LND+ group showed improved OS compared to the lack of left paratracheal lymph node dissection (4LND-) group [hazard ratio (HR) 0.77; 95% confidence interval (CI): 0.62-0.96; P=0.02; I²=84%]. There was no statistical difference between the groups when only studies with propensity score matching (PSM) were compared (HR 0.82; 95% CI: 0.66-1.02; P=0.07; I² =83%). The total complication rate [11.5% vs. 8.0%; risk ratio (RR) 1.45; 95% CI: 1.20-1.74; P<0.001; I² =0], and incidence of vocal cord palsy (2.9% vs. 0.77%; RR 3.64; 95% CI: 1.96-6.78; P<0.001; I² =0) were significantly higher in 4LND+ patients. Differences in other specific complications were not significant. In subgroup analyses, there were no significant differences between groups in OS in patients with LUL (HR 0.71; 95% CI: 0.51-1.01; P=0.05; I² =58%) and LLL (HR 0.91; 95% CI: 0.44-1.88; P=0.80; I²=84%) tumors. Similarly, in patients with stage I NSCLC, no significant difference in OS was observed (HR 0.99; 95% CI: 0.79-1.26; P=0.96; I² =15%).

This meta-analysis provides limited evidence that 4LND+ may offer a survival benefit in patients with left-sided NSCLC. However, the significant heterogeneity observed in the primary analysis and the lack of statistical significance in the PSM/propensity score weighting (PSW) subgroup suggest cautious interpretation of the observed survival benefit. Contrary, it is associated with increased overall complication rates, including vocal cord palsy, which underscores the need for careful patient selection. Given the lack of OS benefit in stage I disease, 4LND+ may be more appropriate for patients with more advanced NSCLC. However, further prospective studies are needed to better define its role.