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Lung Cancer Treatments and Mutations / Lung Cancer Diagnosis and Treatment · Journal article
Frontiers in Oncology · September 8, 2026
A consensus or society position rather than new primary data.
This is a clinical framework synthesizing evidence from recent phase III trials of neoadjuvant and perioperative immunotherapy combinations in stage III NSCLC, proposing risk-adapted, multidisciplinary management strategies. The framework acknowledges that while efficacy has been demonstrated (EFS improvements consistent across trials, modest OS benefit in neoadjuvant nivolumab plus chemotherapy, significant OS advantage in KEYNOTE-671), major uncertainties remain regarding comparative perioperative versus neoadjuvant-only strategies, the contribution of adjuvant immunotherapy, and optimal biomarker-guided adaptation. The authors emphasize that prospective validation of risk-adapted strategies is essential before firm practice changes can be recommended.
Journal article. Patients with stage III NSCLC across the resectability spectrum (resectable and unresectable disease)..
Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival, with modest but clinically meaningful overall survival benefit at five years KEYNOTE-671 demonstrated significant overall survival advantage with perioperative strategy AEGEAN and CheckMate 77T showed consistent event-free survival improvements, with overall survival data still maturing
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Clinicians should tailor management through multidisciplinary assessment accounting for anatomical resectability, nodal burden, tumor biology, and treatment response. For resectable disease with actionable oncogenic alterations, upfront resection followed by adjuvant targeted therapy is preferred; for unresectable stage III disease, definitive chemoradiotherapy with consolidation durvalumab is standard. However, the choice between neoadjuvant-only and perioperative immunotherapy strategies, and the role of biomarker-guided adaptation, remains uncertain and requires prospective validation.
A critical synthesis and clinical framework addressing heterogeneous stage III NSCLC management in the perioperative immunotherapy era, integrating recent phase III trial evidence with expert consensus on risk-adapted strategies.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should tailor management through multidisciplinary assessment accounting for anatomical resectability, nodal burden, tumor biology, and treatment response. For resectable disease with actionable oncogenic alterations, upfront resection followed by adjuvant targeted therapy is preferred; for unresectable stage III disease, definitive chemoradiotherapy with consolidation durvalumab is standard. However, the choice between neoadjuvant-only and perioperative immunotherapy strategies, and the role of biomarker-guided adaptation, remains uncertain and requires prospective validation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous disease, and recent phase III trials have demonstrated the efficacy of neoadjuvant and perioperative chemoimmunotherapy in selected patients. However, translating these data into consistent real-world multidisciplinary decision-making remains challenging because anatomical resectability, nodal burden, tumor biology, and treatment response vary substantially. Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival (EFS), with a modest but clinically meaningful overall survival (OS) benefit at five years. Perioperative strategies appear to extend these benefits: KEYNOTE-671 demonstrated a significant OS advantage, while AEGEAN and CheckMate 77T showed consistent EFS improvements, with OS data still maturing. However, cross-trial comparisons are inherently limited, and the incremental contribution of the adjuvant immunotherapy phase remains unclear. Exploratory subgroup analyses suggest potentially greater benefit in N2 disease, although prospective validation is required. For tumors harboring actionable oncogenic alterations, upfront resection followed by adjuvant targeted therapy remains the preferred strategy, whereas definitive chemoradiotherapy followed by consolidation durvalumab remains standard of care for unresectable stage III disease. Management of stage III NSCLC should be individualized through multidisciplinary assessment. Major uncertainties persist regarding the comparative efficacy of perioperative versus neoadjuvant-only strategies, the contribution of adjuvant immunotherapy, and the role of biomarker-guided treatment adaptation. This clinical framework provides structured guidance to support treatment selection across the heterogeneous spectrum of stage III disease, while recognizing that prospective validation of risk-adapted strategies remains essential.
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