Utility and Future Perspectives of Circulating Tumor DNA Analysis in Non-small Cell Lung Cancer Patients in the Era of Perioperative Chemo-immunotherapy

Perioperative/neoadjuvant chemo-immunotherapy is a standard treatment for patients with resectable non-small cell lung cancer (NSCLC). However, several key clinical questions remain unresolved, including the monitoring of tumor response during neoadjuvant treatment, detection of residual disease after neoadjuvant treatment or after surgery, stratification of recurrence risk, and earlier detection of disease recurrence. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to ad-dress these challenges. Data from several recent clinical trials of perioperative/neoadjuvant chemo-immunotherapy demonstrated that ctDNA clearance before surgery was associated with higher rates of major pathological response. Additionally, landmark ctDNA positivity after surgery identified patients at high risk of disease recurrence, and longitudinal ctDNA monitoring enabled earlier detection of recurrence compared with radiographic surveillance. Several ongoing trials are incorporating ctDNA as a biomarker to guide treatment decisions, including optimizing the duration of neoadjuvant therapy, evaluating the need for surgery, and tailoring adjuvant strategies. These trials, together with further development of ctDNA detection technologies, will clarify the role of ctDNA analysis in refining perioperative treatment strategies and may ultimately enable individualized care in patients with resectable NSCLC. In this review, we discuss the current research data on ctDNA analysis in NSCLC in this era of perioperative chemo-immunotherapy.