ctDNA in Early and Locally Advanced NSCLC: Evidence Review and Clinical Readiness Assessment
This Nature Reviews Clinical Oncology paper synthesizes evidence for ctDNA applications in early-stage and locally advanced non-small-cell lung cancer, where ctDNA detection before or after surgery correlates with higher recurrence risk. Longitudinal monitoring can detect relapse earlier than imaging, and post-chemoradiotherapy ctDNA positivity signals progression risk. The authors conclude that while the evidence is compelling, heterogeneous study designs and small cohorts mean routine clinical use requires interventional trial validation.
The original study
Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?
- Authors
- Normanno N, Morabito A, Rachiglio AM, Sforza V, Landi L, Bria E, et al.
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review
- PMID
- 39833354
Original abstract
Circulating tumour DNA (ctDNA) can be released by cancer cells into biological fluids through apoptosis, necrosis or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA levels correlate with clinical and pathological factors, including histology, tumour size and proliferative status. Currently, ctDNA analysis is recommended for molecular profiling in patients with advanced-stage NSCLC. In this Review, we summarize the increasing evidence suggesting that ctDNA has potential clinical applications in the management of patients with early stage and locally advanced NSCLC. In those with early stage NSCLC, detection of ctDNA before and/or after surgery is associated with a greater risk of disease recurrence. Longitudinal monitoring after surgery can further increase the prognostic value of ctDNA testing and enables detection of disease recurrence earlier than the assessment of clinical or radiological progression. In patients with locally advanced NSCLC, the detection of ctDNA after chemoradiotherapy is also associated with a greater risk of disease progression. Owing to the limited number of patients enrolled and the different technologies used for ctDNA testing in most of the clinical studies performed thus far, their results are not sufficient to currently support the routine clinical use of ctDNA monitoring in patients with early stage or locally advanced NSCLC. Therefore, we discuss the need for interventional studies to provide evidence for implementing ctDNA testing in this setting.