ctDNA for the Evaluation and Management of EGFR-Mutant Non-Small Cell Lung Cancer

Simple Summary Lung cancer patients with a specific gene mutation often undergo tissue biopsies to guide treatment. But what if a simple blood test could do the same? This review explores "liquid biopsies", which detect circulating tumor DNA (ctDNA) in the blood, offering several advantages. For early-stage disease, it could help decide on treatment after surgery. In advanced stages, it can identify genetic changes in the tumor that might affect treatment response. Additionally, tracking ctDNA levels can monitor treatment progress and detect resistance early. While tissue biopsies remain standard, liquid biopsies are becoming a recommended alternative. Ongoing research aims to improve test sensitivity for early detection, refine treatment approaches based on ctDNA results, and explore other bodily fluids for even better detection. Making liquid biopsies more accessible and integrated into routine care could significantly improve lung cancer management.Abstract Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating tumor DNA (ctDNA), in the management of NSCLC with EGFR mutations. While tissue-based genomic testing remains the cornerstone for clinical decision-making, liquid biopsies offer a well-validated, guideline-recommended alternative approach. Ongoing trials integrating ctDNA for EGFR-mutant NSCLC management are also discussed, shedding light on the potential of ctDNA in early-stage disease, including its applications in prognostication, risk stratification, and minimal residual disease detection post-curative intent treatment. For advanced disease, the role of ctDNA in identifying resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) is explored, providing insights into disease progression and guiding treatment decisions. This review also addresses the challenges, including the limitations in sensitivity of current assays for disease recurrence detection, and calls for future studies to refine treatment approaches, standardize reporting, and explore alternative biofluids for enhanced sensitivity. A systematic approach is crucial to address barriers to ctDNA deployment, ensuring equitable access, and facilitating its integration into routine clinical practice.