Detection of Tumor Recurrence via Circulating Tumor DNA Profiling in Patients with Localized Lung Cancer: Clinical Considerations and Challenges

SIMPLE SUMMARY: Circulating tumor DNA is a novel biomarker with emerging uses in the clinical care of patients with cancer, including non-small-cell lung cancer. Already approved for use in various clinical settings in patients with metastatic non-small-cell lung cancer, recent research has focused on the ability of circulating tumor DNA to predict relapse of patients with localized disease after treatment with curative intent. Identifying patients at increased risk of relapse after treatment with curative intent remains challenging, but several groups have identified circulating tumor DNA kinetics as a potential means of aiding our risk stratification. Herein, we discuss current research that identifies longitudinal circulating tumor DNA kinetics as a highly sensitive and specific marker for relapse. Then, we identify important clinical considerations and challenges for moving forward with further studying and eventually using this biomarker for patients with localized disease in clinic. ABSTRACT: Approximately 30% of patients with non-small-cell lung cancer (NSCLC) present with localized/non-metastatic disease and are eligible for surgical resection or other “treatment with curative intent”. Due to the high prevalence of recurrence after treatment, adjuvant therapy is standard care for most patients. The effect of adjuvant chemotherapy is, however, modest, and new tools are needed to identify candidates for adjuvant treatments (chemotherapy, immunotherapy, or targeted therapies), especially since expanded lung cancer screening programs will increase the rate of patients detected with localized NSCLC. Circulating tumor DNA (ctDNA) has shown strong potential to detect minimal residual disease (MRD) and to guide adjuvant therapies. In this manuscript, we review the technical aspects and performances of the main ctDNA sequencing platforms (TRACERx, CAPP-seq) investigated in this purpose, and discuss the potential of this approach to guide or spare adjuvant therapies after definitive treatment of NSCLC.