New ESMO recommendations on the use of ctDNA

Despite circulating tumour DNA (ctDNA) can theoretically give more information on the spatial and temporal heterogeneity of a tumour than traditional tissue genotyping, its use in routine clinical practice requires a careful attention to pre-analytical processing and the selection of the appropriate technology which may influence the results obtained. Newly published recommendations of the ESMO Precision Medicine Working Group provide guidance to medical oncologists on the clinical applications of this tool at any stage of the cancer care course, aiming to address the main technical aspects of testing and provide some quality standards required for decision-making.

Liquid biopsies, and in particular ctDNA detected in plasma, are increasingly used in clinical practice as their minimally invasive nature holds the potential of repeated sampling over time. ctDNA release is believed to be proportional to tumour growth, with the fastest-growing tumour clones shedding the largest amount of DNA in plasma. Multiple technologies and modalities to detect, extract and quantify ctDNA are currently available, making a deep understanding of the analytical and clinical validity and utility of lab developed or commercial ctDNA assays essential to address specific scientific and clinical questions.

In the paper published in the Annals of Oncology, the group of experts highlight the main aspects to consider before testing, when reading a report and then translating the findings into action in clinics (Figure), including some considerations on the high rates of false negative or non-informative results, limitations for the detection of specific aberrations and tumour-specific recommendations.

In the new ESMO recommendations, some insights are also given about other possible applications of ctDNA in the future like screening, molecular residual disease assessment, molecular relapse monitoring and early assessment of treatment response of which evidence of utility is still lacking.