Liquid biopsy in newly diagnosed patients with locoregional (I-IIIA) non-small cell lung cancer

ABSTRACT

Introduction: Liquid biopsy is a promising method for the management of lung cancer, but previous studies focused mainly on patients with advanced-stage disease. As the methodology has progressed for the detection of circulating tumor DNA (ctDNA) and its aberrant methylation, researchers are gradually investigating the utility of liquid biopsy in early-stage patients. As a result, liquid biopsy has shown its potential for the application in patients with early- and locally advanced-stage non-small cell lung cancer (NSCLC).

Areas covered: This review summarizes the utility of liquid biopsy in NSCLC and provide an outlook for future development. We focus on the role of ctDNA and its aberrant methylation in patients with stage IA to stageⅢA NSCLC, in the field of early detection and screening, perioperative management, and postoperative surveillance.

Expert opinion: Liquid biopsy has shown the potential for clinical application of early-stage patients but has not been routinely applied yet. The utilization of liquid biopsy will be promoted by improved detection methods and data from well-designed clinical trials. With the development of precision medicine, liquid biopsy will likely play an increasingly important clinical role.

KEYWORDS:

• Lung cancer
• circulating tumor DNA
• minimal residual disease
• liquid biopsy

Article highlights

• Liquid biopsy can provide an auxiliary means of differential diagnosis for lung cancer, when screening by LDCT. Detection of ctDNA and miRNAs has shown great potential for early detection. Several platforms based on liquid biopsy have been designed for screening of multiple cancer types. Prospective clinical trials should be conducted to explore the optimization of screening strategies in high-risk and healthy populations.

• ctDNA detection can be used to infer the tumor mutational burden (TMB) and predict immunotherapy responders. By analyzing mutations of patients with detectable ctDNA, potential candidates for EGFR-TKI treatment can be selected. Considering the advantage of noninvasiveness, liquid biopsy may become a practical method for treatment selection.

• With the development of targeted therapy and immunotherapy, the superiority of liquid biopsy in the perioperative management of lung cancer patients improves. ctDNA can reflect tumor genetic changes, detect tumor progression and drug-resistant mutations during the treatment of EGFR-TKI. Patients with pseudoprogression can be evaluated by ctDNA detection, when taking immune checkpoint inhibitors.

• Previous studies have shown satisfactory results for lung cancer surveillance by ctDNA detection, although further clinical trials are still needed. As a sensitive and cost-effective method, ctDNA methylation detection has the potential to be utilized in lung cancer surveillance. Some ongoing clinical trials may describe the characteristics of ctDNA methylation in postoperative patients in the near future.

• MRD detection was related to unfavorable prognosis in surgical lung cancer patients. However, ctDNA detection-based adjuvant therapy needs validation in large-scale randomized controlled trials.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they currently have grant funding monitoring in newly diagnosed patients with loco-regional NSCLC. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [No. 81602001].