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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.
Neoadjuvant chemoimmunotherapy shows promise for stage-II non-small cell lung cancer, improving survival and pathological response compared to upfront surgery and chemotherapy. Further stratification tools are needed to identify high-risk patients for optimal treatment selection.
Area of Science:
- Medical Oncology
- Thoracic Surgery
- Clinical Trials
Background:
- Neoadjuvant chemoimmunotherapy adoption in stage-II non-small cell lung cancer (NSCLC) lacks clear survival advantages and patient stratification methods.
- Randomized clinical trials have yielded mixed results regarding the efficacy of neoadjuvant chemoimmunotherapy in NSCLC.
Purpose of the Study:
- To compare the overall survival of stage-II NSCLC patients receiving neoadjuvant chemoimmunotherapy versus upfront surgery.
- To evaluate the pathological response and survival outcomes of neoadjuvant chemoimmunotherapy compared to chemotherapy in stage-II NSCLC.
Main Methods:
- Individual patient data (IPD) meta-analysis of phase-3 randomized-controlled trials for neoadjuvant chemoimmunotherapy versus upfront surgery.
- Utilized the IPDfromKM method for data extraction and Cox-regression analyses to estimate hazard ratios (HR) and 95% confidence intervals (95%CI).
- Conducted meta-analysis and meta-regression comparing neoadjuvant chemoimmunotherapy and chemotherapy, deriving relative risks (RR) with 95%CI.
Main Results:
- Neoadjuvant chemoimmunotherapy improved survival versus upfront surgery in the 8th edition TNM database (HR=0.68, p=0.002) but not the 9th edition (HR=0.82, p=0.10).
- Chemoimmunotherapy significantly improved pathologic complete response (RR=6.19) and major pathologic response (RR=3.08) compared to chemotherapy.
- Chemoimmunotherapy also improved event-free survival (HR=0.66) and overall survival (HR=0.68) compared to chemotherapy, with comparable surgical outcomes.
Conclusions:
- Neoadjuvant chemoimmunotherapy demonstrates encouraging results for stage-II lung cancer, improving long-term outcomes and pathological response.
- Stratification tools are essential to identify high-risk patients for neoadjuvant chemoimmunotherapy selection.
- Chemoimmunotherapy offers superior pathological and survival benefits over chemotherapy with similar surgical safety profiles.
