Nodal upstaging and neoadjuvant therapy in lung adenocarcinoma: Evidence of a missed opportunity?

Nodal upstaging at time of lung adenocarcinoma resection is associated with worse outcomes. Using a large national cohort, we studied rates of upstaging and outcomes of patients with clinical stage IA-IIA disease who were upstaged due to positive nodes at surgery compared to patients with clinically node-positive stage IIB/IIIA who received neoadjuvant therapy (NT).

We used National Cancer Database data from 2018 to 2022. Nodal upstaging was defined as patients clinical stage IA-IIA found to be pathologic stage IIB/IIIA due to positive nodes at surgery. Upstaged patients were compared to patients who were clinically node-positive stage IIB/IIIA and who received NT. Kaplan-Meier curves, log-rank tests, and adjusted Cox proportional hazard models were used to analyze survival.

Out of a total of 33,016 patients identified as clinical stage IA-IIA and node-negative, 4301 (13.0%) were upstaged due to positive nodes at surgery, with this rate increasing to 23.3% in clinical stage IIA patients. Patients who were clinical stage IA-IIA but upstaged at surgery were then compared to patients who were clinical stage IIB/IIIA and received NT (n = 1569). In an adjusted model, patients who were upstaged demonstrated worse survival (1.20 [1.00-1.44], P = .04).

In this large national cohort, a nodal upstaging rate of 13% was observed in patients undergoing lung resection for adenocarcinoma, and patients with nodal upstaging demonstrated worse survival compared to clinically node-positive patients who received NT. Patients who were clinical IIA had a higher rate of upstaging (23.3%), and investigation of empiric NT in this subpopulation may be warranted.