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

IPBronch Review

🎯 Background & Rationale

The management of non-metastatic non-small-cell lung cancer (NSCLC) has evolved rapidly with multimodality strategies, biomarker-driven therapies, and immunotherapy. However, significant variations in real-world clinical practice persist due to ambiguities and conflicting recommendations across major international guidelines, particularly in complex or borderline scenarios. This study addresses these clinical "gray zones" by establishing an international multidisciplinary consensus.

👥 Study Design & Population

This is an international, multidisciplinary expert consensus study utilizing a modified Delphi methodology. The panel comprised 89 international experts in thoracic oncology, including medical oncologists, interventional pulmonologists/pulmonologists, thoracic surgeons, radiation oncologists, radiologists, and pathologists from diverse geographic regions.

📈 Methodology & Rigor

A modified Delphi process was conducted, incorporating a 3-day in-person meeting in Barcelona (September 2025). Prior to the meeting, expert working groups drafted statements based on literature reviews and clinical experience, which were refined by a steering committee. Panelists independently rated 96 clinical statements using a 9-point Likert scale via a secure digital platform. Consensus was predefined as $\ge$75% of ratings falling in the 7–9 range, and rejection as $\ge$75% in the 1–3 range.

🔬 Key Findings [or Planned Endpoints]

Out of 96 evaluated clinical statements:

  • Consensus Achieved (64%): 62 statements reached agreement. Strong consensus supported routine staging with FDG PET–CT, histologic confirmation of suspicious mediastinal nodes ($\ge$15 mm or FDG-avid), reflex PD-L1 testing and DNA-based NGS at diagnosis, standardized post-neoadjuvant pathological assessment (pCR evaluation), and sublobar anatomic resection for peripheral node-negative tumors $\le$2 cm. Consolidation durvalumab after definitive chemoradiotherapy was endorsed for unresectable stage II–III disease regardless of PD-L1 expression.
  • No Consensus / Controversial (32%): 31 statements remained without consensus, including the routine use of brain MRI in stage I disease, invasive mediastinal restaging after induction therapy, routine RNA-based fusion testing, and the clinical utility of liquid biopsy/ctDNA to guide perioperative treatment decisions.
  • Rejected (3%): 3 statements were rejected, including the routine use of major pathologic response (MPR) to determine adjuvant therapy, postoperative MRD results to guide the type or duration of adjuvant therapy, and concurrent administration of adjuvant immunotherapy and postoperative radiotherapy (PORT).
  • Note: Exact numerical percentages for individual statements are fully detailed in the published consensus tables.

⚖️ Critical Appraisal

While the modified Delphi method is a validated tool to synthesize expert opinion in the absence of robust randomized trial data, consensus inherently represents expert opinion rather than high-level Level 1 empirical evidence. The panel included a broad international multidisciplinary representation, reducing single-specialty bias. However, regional variations in healthcare resource availability, local drug approvals, and differing guideline interpretations globally may limit the universal generalizability of certain non-consensus items.

💡 The Clinical Bottom Line

This international consensus provides a pragmatic decision-support tool for pulmonologists and thoracic oncologists navigating complex, real-world scenarios not fully resolved by standard guidelines. For the bronchoscopy and interventional pulmonology suite, it reinforces the mandate for thorough initial staging (systematic FDG PET–CT and tissue acquisition of suspicious nodes), tissue stewardship to preserve material for molecular profiling, and collaborative multidisciplinary planning for perioperative and locally advanced multimodality therapies.


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.
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