Resectability in the Era of Modern Systemic Therapy for Non-Small Cell Lung Cancer (NSCLC)

The management of non-small cell lung cancer (NSCLC) has changed substantially with the integration of modern systemic therapies, including immunotherapy, targeted therapy, and multimodal perioperative strategies. These advances are reshaping how clinicians define operability and resectability, particularly in patients with locally advanced disease, oligometastatic presentations, or tumors initially considered borderline resectable. In parallel, improvements in imaging, staging, molecular profiling, and response assessment have made treatment planning more precise, but also more complex. Surgeons now play a central role within multidisciplinary teams that must decide not only whether a tumor can be removed, but also when surgery should be performed, after which systemic treatment, and for which biological or clinical subgroups. As a result, traditional surgical decision-making frameworks are being challenged and refined in real time.This Research Topic aims to examine how modern systemic therapy is redefining resectability in NSCLC and to identify the clinical, pathological, radiological, and molecular factors that should guide treatment selection. A major challenge in current practice is the lack of uniform criteria for determining resectability after induction or neoadjuvant treatment, especially as major pathological responses, nodal downstaging, and radiographic changes do not always align. Questions also remain regarding patient selection for surgery after immunotherapy or targeted therapy, the role of salvage and conversion surgery, perioperative risk after systemic treatment, and the best endpoints for evaluating outcomes in this new therapeutic landscape.By bringing together surgical oncologists, thoracic surgeons, medical oncologists, radiation oncologists, pathologists, and translational researchers, this collection seeks to clarify contemporary definitions of resectability and to highlight evidence that can support multidisciplinary decision-making. It will also provide a forum for discussing emerging strategies, unresolved controversies, and future directions for integrating surgery into personalized NSCLC care.This Research Topic welcomes contributions addressing the evolving role of surgery across resectable, borderline resectable, and initially unresectable NSCLC in the setting of modern systemic therapy. We are particularly interested in clinically relevant and multidisciplinary studies that inform patient selection, timing of surgery, technical feasibility, perioperative outcomes, and long-term oncologic benefit.We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:- definitions and assessment of resectability after neoadjuvant therapy- immunotherapy and chemo-immunotherapy in operable NSCLC- targeted therapies and surgery in oncogene-driven disease- conversion, salvage, and rescue surgery- nodal downstaging, pathological response, and biomarkers of surgical benefit- technical challenges and perioperative outcomes after systemic treatment- multidisciplinary decision-making and treatment sequencing- future trial designs and clinically meaningful endpoints in perioperative NSCLCPlease note: manuscripts consisting solely of bioinformatics or computational analysis of sole public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Jorge Humberto Rodriguez-Quintero, Francesco Petrella Source: https://www.frontiersin.org/research-topics/79403/resectability-in-the-era-of-modern-systemic-therapy-for-non-small-cell-lung-cancer-nsclc