Actionable driver gene alterations in early-stage non-small cell lung cancer: a review

Early-stage (I–III) non-small cell lung cancer (NSCLC) can harbor oncogenic driver mutations that have critical implications for patient management and outcomes. Historically, molecular testing in resected NSCLC was limited, often focusing only on EGFR mutations or ALK rearrangements due to the lack of approved targeted therapies in the adjuvant setting until recently. However, with the advent of next-generation sequencing (NGS) and emerging evidence of actionable mutations in early-stage tumors, comprehensive genomic profiling is becoming increasingly relevant in this setting. Identifying these alterations is clinically significant: the presence of specific mutations can directly influence adjuvant treatment planning and refine the role of immunotherapy. Beyond guiding therapy selection, molecular profiles also provide prognostic insight: certain driver subtypes have been associated with higher recurrence risk in early-stage patients, suggesting a need for intensified surveillance. The expanding role of NGS enables personalized postoperative strategies, including tailored follow-up intervals and potential circulating tumor DNA monitoring to detect minimal residual disease. In summary, incorporating broad molecular testing in early-stage NSCLC empowers clinicians to optimize adjuvant treatment decisions and surveillance strategies, ultimately aiming to improve patient outcomes through precision oncology.