Postoperative radiotherapy (PORT) for resected locally advanced non-small cell lung cancer (rLA-NSCLC) has been the subject of debate for decades. Early meta-analyses suggested harm except possibly in N2 disease, and subsequent practice was influenced by a secondary analysis of the ANITA trial that demonstrated an overall survival benefit in patients with pN2 disease. More recent randomized trials in this population, including Lung ART, did not show a disease-free survival benefit. The reduction in mediastinal relapse observed with PORT was counterbalanced by increased cardiopulmonary toxicity, which was likely related to the use of less conformal techniques.

The treatment landscape has shifted with the introduction of neoadjuvant chemo-immunotherapy, which achieves pathological complete response (pCR) rates of up to 25 percent. Patients who do not achieve pCR remain at high risk for locoregional relapse, often in thoracic lymph nodes. Because additional systemic therapy may provide limited benefit for these poor responders, there is renewed interest in evaluating modern, precision-based PORT as a strategy for improving outcomes in this high-risk pN2 population.

This Research Topic will examine the role of postoperative radiotherapy (PORT) in resected locally advanced non-small cell lung cancer (rLA-NSCLC) in the era of neoadjuvant immunotherapy. The aim is to understand whether modern, precision-based PORT can provide meaningful benefit for patients at highest risk of locoregional relapse, particularly those with persistent pN2 disease after chemo-immunotherapy. The collection will explore advances in patient selection, integration with contemporary systemic approaches, and technical innovations that improve the balance between tumor control and cardiopulmonary toxicity. By drawing on clinical, translational, and technical perspectives, this work will provide a foundation for evidence-based recommendations and future clinical trials that address the unique challenges of the of treating NSCLC in the neoadjuvant immunotherapy era.

We invite original research, reviews, clinical trial protocols, and expert perspectives that address the evolving role of postoperative radiotherapy (PORT) for resected locally advanced non-small cell lung cancer (rLA-NSCLC) in the neoadjuvant immunotherapy era. Submissions may focus on:

• Patient selection strategies for PORT after chemo-immunotherapy, including pathological and imaging-based response criteria.

• Advances in radiation planning and delivery such as intensity-modulated radiotherapy (IMRT), proton therapy, hypofractionation, and involved-station targeting.

• Strategies to minimize cardiopulmonary toxicity while maintaining tumor control.

• Translational research on the interaction between radiotherapy and immune modulation.

• Health services and comparative effectiveness research on PORT adoption and access in diverse practice settings.

• Cost–benefit and value-based analyses of modern PORT techniques in the context of evolving systemic therapy standards.

The aim is to integrate clinical, technical, economic, and translational insights into a coherent framework that guides real-world practice and informs the design of future clinical trials.

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

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The Role of PORT (Post Operative Radiotherapy) for LA-NSCLC in the era of immunotherapy