Rethinking Operability and Multimodal Decision-Making in Early-Stage and Stage III NSCLC: Impact of Perioperative Immunotherapy and Advanced Imaging

The introduction of perioperative immunotherapy is transforming the management of early-stage and stage III non-small cell lung cancer (NSCLC), particularly in patients with limited or marginal resectability. Traditional criteria used to define operability are being challenged as neoadjuvant and induction chemoimmunotherapy reshape tumor burden, radiologic appearance, and expected outcomes. These regimens expand the pool of patients who may become candidates for curative-intent resection, yet they also introduce uncertainty regarding which patients truly benefit from surgery, and when non-surgical or combined-modality approaches are preferable. In parallel, indications and strategies for radiotherapy are evolving in both early-stage and locally advanced disease, while advanced thoracic imaging modalities—including high-resolution CT, PET/CT, MRI, and artificial intelligence-driven radiomics—are becoming central to staging, response assessment, and treatment planning.This Research Topic aims to clarify how operability and resectability should be defined and applied in early-stage and stage III NSCLC in the era of perioperative immunotherapy. We seek to understand which patients should proceed to surgery after neoadjuvant or induction chemoimmunotherapy, which patients should not—and why—and how systemic, imaging, and clinical factors can be integrated into robust decision frameworks. A key objective is to refine patient selection for surgery versus definitive radiotherapy or combined multimodal approaches, addressing how immunotherapy-induced changes influence technical feasibility, oncologic benefit, and long-term outcomes. The collection will also explore the evolving role and timing of radiotherapy in patients with limited resectability, and how advanced imaging can be used to better characterize response, residual disease, and nodal involvement, thus improving multidisciplinary treatment planning.Within this context, the Scope of the Research Topic encompasses early-stage (including higher-risk resectable disease) and stage III NSCLC in which perioperative immunotherapy is considered or delivered, with a focus on preoperative and non-operative decision-making and deliberate exclusion of the strictly postoperative radiotherapy (PORT) setting. We welcome submissions that address, but are not limited to, the following themes:- Evolving definitions and clinical frameworks for resectability and operability in early-stage and stage III NSCLC treated with perioperative immunotherapy- Real-world and trial-based data on outcomes of surgery versus non-surgical or combined-modality strategies after neoadjuvant or induction chemoimmunotherapy- The role and timing of radiotherapy in multimodal regimens for patients with limited or uncertain resectability, before or instead of surgery- Advanced thoracic imaging techniques (e.g., functional imaging, radiomics, AI-based analysis) for staging, response assessment, and surgical or radiotherapy planning- Integration of imaging, molecular, and clinical risk models into multidisciplinary tumor board decision-making for perioperative immunotherapy candidates- Role of multidisciplinary tumor boards in borderline resectable or borderline operable NSCLC, including inter-tumor board variability and its impact on treatment recommendations and outcomes- Methodological innovations in trial design and real-world evidence for early-stage and locally advanced NSCLC receiving perioperative immunotherapyWe invite original research articles, comprehensive and mini-reviews, clinical trial protocols, consensus or position papers, and expert perspectives that advance evidence-based, imaging-informed, and multidisciplinary decision-making for patients with early-stage and stage III NSCLC in the perioperative immunotherapy era.Priv.-Doz. Dr. Gerald Schmid-Bindert declares he is a full time employee of AstraZeneca, Germany.Priv.-Doz Dr. med. Wilfried E.E. Eberhardt declares that they have received an honoraria for Advisory Board function from Astra Zeneca, Roche, MSD, BMS, PFIZER, Boehringer Ingelheim, Amgen, Sanofi, Regeneron, BEONE, GSK, Onkowissen.de, Eli Lilly, Pierre Fabre, Takeda, Daichii Sankyo. They have also received honoraria for Educational Lectures from Astra Zeneca, Roche, MSD, BMS, PFIZER, Amgen, Sanofi, Regeneron, BEONE, Onkowissen.de, Eli Lilly, Pierre Fabre, Takeda, Daichii Sankyo. They have also declared an Investigator Initiated Trial funded by an AstraZeneca Unrestricted Grant to the Institution. Topic editors: PD D. Gerald Schmid-Bindert, Wilfried Ernst Erich Eberhardt, Xiaonan Cui, Eric Dominic Roessner Source: https://www.frontiersin.org/research-topics/76535/rethinking-operability-and-multimodal-decision-making-in-early-stage-and-stage-iii-nsclc-impact-of-perioperative-immunotherapy-and-advanced-imaging