Bridging evidence and practice: international multidisciplinary consensus on non-metastatic NSCLC

Background: The management of non-metastatic non-small-cell lung cancer (NSCLC) has become increasingly complex with the integration of multimodality strategies and biomarker-driven approaches. Several clinically relevant areas remain insufficiently defined by current evidence and international guidelines. We conducted an international multidisciplinary consensus to address major areas of uncertainty in real-world practice. Methods: A modified Delphi process was conducted during a 3-day in-person meeting in Barcelona, Spain (3-5 September 2025). Eighty-nine thoracic oncology experts independently rated predefined clinical statements developed by working groups and refined by a steering committee. Agreement was assessed using a 9-point Likert scale. Consensus was predefined as ≥75% of ratings in the 7-9 range; rejection as ≥75% in the 1-3 range. Results: Ninety-six statements were evaluated. Consensus was achieved for 62 statements (64%), 31 (32%) remained without consensus, and 3 (3%) were rejected. Consensus supported routine FDG PET-CT for staging, histologic confirmation of suspicious mediastinal nodes, reflex PD-L1 testing and DNA-based next-generation sequencing at diagnosis, standardized post-neoadjuvant pathologic assessment, and sublobar resection with systematic nodal evaluation for selected peripheral node-negative tumors ≤2 cm. Consolidation durvalumab after definitive chemoradiotherapy was supported irrespective of PD-L1 expression in unresectable stage II-III disease. Persistent areas of controversy included brain MRI in stage I disease, mediastinal restaging after induction therapy, routine RNA-based testing, and the use of circulating tumor DNA/minimal residual disease to guide perioperative decisions. Conclusions: This international consensus provides structured expert guidance in areas of uncertainty in non-metastatic NSCLC and highlights priorities for future prospective research.