Diagnostic Utility of Liquid Biopsy to Analyze Circulating Tumor DNA Via Next-Generation Sequencing

OBJECTIVES: This report evaluates the potential of Liquid Biopsy (LB) for diagnostic purpose by analyzing circulating tumor DNA (ctDNA) via next-generation sequencing (NGS) in breast, lung, and colorectal cancer, aiming to assess its inclusion in the Catalan Health System (CHS) benefit package.

METHODS: An umbrella review was conducted to evaluate LB diagnostic utility for analyzing ctDNA via NGS compared to tissue biopsy. Data from NGS panels were manually sourced and presented as narrative review. Recommendations by leading scientific societies (SS) on LB use were also reviewed. Finally, a protocol was designed to outline guidelines for a budget impact analysis (BIA) of this technology’s implementation in the CHS.

RESULTS: The umbrella review found no existing systematic reviews (SR) on early cancer diagnosis or screening. However, some SR with meta-analysis (MA) were identified on the diagnostic utility in establishing the molecular profile of the tumor in breast cancer (PIK3CA), non-small cell lung cancer (NSCLC) (EGFR, ALK, ROS-1, BRAF, RET, and MET), or colorectal cancer (RAS [KRAS, NRAS]. Eleven commercial NGS panels were identified, with only two having a CE mark for profiling tumor mutations or selecting therapy. SS generally recommend LB as the first choice in advanced disease for tumor genotyping only when there are no tissue samples or when urgent therapeutic decisions need to be made. The proposed BIA protocol aims to estimate the expected variations in the financial budget of the CHS.

CONCLUSIONS: Existing evidence of LB to analyze ctDNA via NGS from SR with MA is limited to the molecular profile application and for certain target genes. Most NGS panels allow the detection of SNV, indels, CNV, and fusions. SS recommendations suggest that LB may be complementary to tissue biopsy. The BIA will help decision-makers understand the potential costs and economic benefits in different scenarios, facilitating better resource management.