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Stage III non-small cell lung cancer (NSCLC) accounts for approximately 30% of newly diagnosed NSCLC cases, and the vast majority of these patients present with unresectable disease. Its unresectable nature makes definitive chemoradiotherapy the cornerstone of treatment. In recent years, with immune checkpoint inhibitors (ICIs) becoming a major research focus in lung cancer, increasing evidence demonstrates that the combination of radiotherapy and immunotherapy (iRT) can significantly enhance antitumor efficacy through synergistic mechanisms. The groundbreaking results of the landmark PACIFIC trial further established consolidation immunotherapy following concurrent chemoradiotherapy as the standard of care. However, controversies persist regarding optimal radiotherapy strategies, timing of immune intervention, management of adverse reactions, and exploration of biomarkers. This review aims to systematically elucidate the synergistic mechanisms of iRT, summarize clinical trial advances under different iRT treatment modalities (concurrent, consolidation and induction), and provide an in-depth analysis of key issues in current clinical practice along with future research directions.
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