Role of radiotherapy in advanced oncogenic-driven oligometastatic non-small cell lung cancer patients: a narrative review.

Background and Objective: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), improving survival significantly. However, the integration of TKIs with radiotherapy (RT) for oligometastatic EGFR-mutant NSCLC remains an emerging strategy, with questions surrounding the optimal timing of RT intervention. This review seeks to examine recent insights into the timing of RT in relation to disease progression and to investigate the radiosensitizing effects of TKIs. Methods: A comprehensive literature search was conducted using PubMed, Web of Science and ClinicalTrials.gov, focusing on studies from the three decades published in English. Key terms included "oncogenic-driven NSCLC", "oligometastasis", "radiotherapy", "TKI combination therapy" and "local therapy". Key Content and Findings: The review assesses studies evaluating two RT intervention timings: after disease progression (oligoprogressive state) and during stable disease (oligoresidual state). Findings indicate that RT timing can influence patient outcomes, with preclinical studies showing that TKIs enhance radiosensitivity through mechanisms that impede deoxyribonucleic acid (DNA) repair, alter cell cycle phases, and inhibit angiogenesis. Conclusions: The combination of TKIs with RT presents promising survival benefits for oligometastatic EGFR-mutant NSCLC patients, yet timing remains critical to optimizing therapeutic outcomes. This review highlights the need for future research to refine RT protocols, guide clinical practice, and inform policy for advanced NSCLC management, potentially impacting survival and quality of life in this patient population.