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Published on: February 27, 2026
Stage II Non-Small Cell Lung Cancer: Upfront Surgery or Neoadjuvant Chemoimmunotherapy
Riccardo Tajè1, Filippo Tommaso Gallina2, Jonathan David Spicer3
1Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada; Department of Thoracic Surgery, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) "Regina Elena" National Cancer Institute, Rome, Italy.
Background:
Neoadjuvant chemoimmunotherapy adoption in stage II non-small cell lung cancer is shrouded by lack of clear survival advantages and stratification across randomized clinical trials.
Methods:
An individual patient data (IPD) meta-analysis was conducted comparing overall survival of stage II patients (according to the American Joint Committee on Cancer TNM staging, eighth edition) receiving neoadjuvant chemoimmunotherapy in phase 3 randomized controlled trials with overall survival of patients undergoing upfront surgery included in the pathologic eighth and ninth edition TNM databases. Individual patient data were extracted using the individual patient data from Kaplan-Meier survival curves (IPDfromKM) method. Cox regression analyses estimated hazard ratios (HRs) and relative 95% (CIs). Meta-analysis and metaregression comparing neoadjuvant chemoimmunotherapy and chemotherapy were also conducted. Relative risk (RR) with 95% CI was derived.
Results:
Overall survival IPD were extracted from 275 stage II patients receiving chemoimmunotherapy and from 6864 (eighth edition) and 7342 (ninth edition) patients undergoing upfront surgery in the pathologic TNM-database. Neoadjuvant chemoimmunotherapy improved survival compared with upfront surgery in the eighth edition TNM database (HR, 0.68; 95% CI, 0.53-0.87; P = .002) but yielded similar survival compared with the ninth edition (HR, 0.82; 95% CI, 0.64-1.1; P = .10). Compared with chemotherapy, pathologic complete response (RR, 6.19; 95% CI, 3.37-10.27; P < .001) and major pathologic response (RR, 3.08; 95% CI, 2.27-4.16; P < .001) favored neoadjuvant chemoimmunotherapy. Similarly, chemoimmunotherapy improved event-free survival (HR, 0.66; 95% CI, 0.52-0.82; P 0.001) and overall survival (HR, 0.68; 95% CI, 0.50-0.92; P = .01). Similar rates of canceled surgery, open surgery, pneumonectomy, conversion from minimally invasive to open surgery, and positive margin were found. The percentage of stage II patients did not modulate surgical-related adverse events, 90-day mortality, and adjuvant treatment receipt.
Conclusions:
Neoadjuvant chemoimmunotherapy has encouraging results in stage II lung cancer, but stratification tools are warranted to select high-risk patients. Compared with chemotherapy, chemoimmunotherapy improves both long-term outcomes and pathologic response with comparable surgical outcomes.
