Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease (MRD) or molecular relapse (MR), has high evidence of clinical validity in anticipating future relapse in many cancers. MRD/MR detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations prior to clinical progression, and in screening asymptomatic people for cancer. Recommendation for reporting of results, future development of ctDNA assays, and future clinical research are made.
View details for DOI 10.1016/j.annonc.2022.05.520
View details for PubMedID 35809752