Mutation testing using cell-free (cf) DNA is becoming increasingly common in oncology, particularly as a tool in tumors that commonly have driver mutations, such as non-small cell lung cancer. Circulating cf tumor DNA in the plasma is now routinely being used alongside traditional tissue-based testing to guide treatment selection and detect resistance mutations upon progression. Given the increasing prevalence of this technique and the importance of accurate results, a European expert panel recently convened to discuss challenges associated with cfDNA testing, including the lack of standardization between different centers, inconsistent quality control, and the impact of false-negative testing. In the consensus statement resulting from this discussion, the panel highlighted the growing importance of cfDNA mutation testing and the need for standardized procedures, commenting, “If implemented well and performed at high quality, it can be a reliable, robust, reproducible, cost-effective, and accurate test with fast turnaround time.” However, the science and infrastructure has actually not yet reached that point in general practice. The panel noted the variability in testing procedures between centers, and provided general recommendations for cfDNA extraction, choice of assay, test validation, and confirmation of negative results.
High Altitude: The cfDNA as a testing approach is increasingly utilized for the clinical development of multiple targeted therapies, especially in cancer types where tissue samples are typically limited . At the most recent American Society for Clinical Oncology meeting, there were over 100 presentations incorporating cfDNA for mutation testing, highlighting both the prevalence of this technique and the wide variety of potential applications. For example, one study focused on cfDNA as a method to detect treatment resistance in patients with breast cancer undergoing chemotherapy, while another evaluated genome-wide cfDNA screening as a potential tool for early detection and monitoring of cancer. As cfDNA testing becomes increasingly integrated into both clinical trials and clinical practice, it will be essential to ensure standardized testing practices. The consensus paper underscores the variability in testing practices between centers and the different testing technologies, emphasizing the need for all publications regarding cfDNA research to include all the variables discussed in this paper so that the analyses can be placed in the appropriate context.
Ground Level: While cfDNA testing largely remains a tool for clinical trials, its prevalence in routine clinical practice is growing. Liquid biopsy testing has numerous potential benefits over conventional diagnostic biopsy. As it becomes more common, the need for standardization is paramount. At the community practice level, it is likely that cfDNA testing will be outsourced to centralized laboratories. However, it will be important to be aware of recommendations for when and how to use cfDNA testing and how to best collect and handle the blood samples. This consensus statement may be a valuable resource for understanding the limitations and potential variability of cfDNA testing technology when interpreting the results. It is also an important step toward further harmonization and standardization of this promising technique.