Examined lymph node count as an independent predictive biomarker for adjuvant systemic therapy efficacy in stage IB lung adenocarcinoma

Adjuvant systemic therapy (AST) utility for stage IB lung adenocarcinoma (LUAD) remains controversial due to the lack of objective metrics for staging adequacy. We aimed to establish an evidence-based threshold for "unknown nodal status" (Nx) and evaluate examined lymph node (ELN) count as a predictive biomarker for AST benefit.

Data from a multicenter cohort (N = 443) and SEER database (N = 4,636) were analyzed. Adjuvant systemic therapy (AST) in this study specifically referred to traditional platinum-based doublet chemotherapy. LOWESS regression identified mortality risk inflection points. Propensity score matching (PSM, SMD ≤ 0.12) evaluated AST efficacy across ELN strata.

LOWESS modeling identified 11 ELNs as the optimal staging threshold. In the local cohort, patients with < 11 ELNs without AST had significantly worse survival ( P < 0.0001); however, AST was associated with significantly improved survival in this subgroup(Adjusted HR 0.24, 95% CI 0.07-0.89, P = 0.033). This compensatory trend was corroborated by SEER (P = 0.0033). Conversely, for thoroughly evaluated "true N0" patients (≥ 11 ELNs), AST provided no survival improvement (Adjusted HR 0.94, 95% CI 0.27-3.19, P = 0.916).

ELN count is a robust gatekeeper for AST efficacy. An ELN < 11 could help clarify Nx status and serve as a strong clinical indicator suggesting potential benefit from AST in stage IB LUAD.

The study was approved by the Ethics Committee of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (IRB -24/660-4940). All participants provided written informed consent.