Longitudinal ctDNA profiling in precision oncology and immunο-oncology

Serial analysis of circulating tumor DNA (ctDNA) over the disease course is emerging as a prognostic, predictive and patient-monitoring biomarker. In the metastatic setting, several multigene ctDNA assays have been approved or recommended by regulatory organizations for personalized targeted therapy, especially for lung cancer. By contrast, in nonmetastatic disease, detection of ctDNA resulting from minimal residual disease (MRD) following multimodal treatment with curative intent presents major technical challenges. Several studies using tumor genotyping-informed serial ctDNA profiling have provided promising findings on the sensitivity and specificity of ctDNA in predicting the risk of recurrence. We discuss progress, limitations and future perspectives relating to the use of ctDNA as a biomarker to guide targeted therapy in metastatic disease, as well as the use of ctDNA MRD detection to guide adjuvant treatment in the nonmetastatic setting.