Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?

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.