Insufficient Evidence of Clinical Validity and Utility for the Majority of ctDNA Assays in Advanced Cancer

Robust research is needed in several areas to enable development of clinical practice recommendations

An Expert Panel from the American Society of Clinical Oncology (ASCO) and the College of American Pathologists conducted a literature review on the use of circulating tumour DNA (ctDNA) assays for solid tumours. Some ctDNA assays have demonstrated clinical validity and utility in certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in that setting. Considering the rapid pace of research, re-evaluation of the literature will shortly be needed. The article is published in the JCO.

The use of assays that assess genomic variants in ctDNA is increasing in the oncology practice, despite uncertainties in term of pre-analytical considerations, analytical validity, and clinical validity and utility. The joint panel of oncology and pathology experts reviewed available evidence and developed the paper about ctDNA assays as a cancer biomarker. The review is limited to analysis of variants in ctDNA for solid tumours and the analysis of sequence or copy number variants in DNA.

A literature search was completed on 20 March 2017. The search strategies were developed in collaboration with a medical librarian for the concepts of liquid biopsies; blood; cancer abnormalities; and pre-analytical, analytical, interpretation, reporting, utility, and validity variables. A total of 1338 unique publications were identified in the search and 390 articles were selected for full-text review. The Expert Panel supplied an additional 31 references. In total, 77 articles were selected for inclusion in the review.

The expert panel concluded that some ctDNA assays have demonstrated clinical validity and utility in certain types of advanced cancer. However, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer with the exception of those with demonstrated clinical utility or those with regulatory approval.

Evidence shows discordance between the results of ctDNA assays and genotyping tumour specimens and supports tumour tissue genotyping to confirm undetected results from ctDNA tests.

There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity and clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial.

The expert panel concluded that robust research is needed in several areas to enable development of clinical practice recommendations. It is highly likely that in coming period evidence will emerge to enable better assessment of the clinical validity and utility of ctDNA assays. 

Reference

Merker JD, Oxnard GR, Compton C, et al. Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol 2018 Mar 5:JCO2017768671. doi: 10.1200/JCO.2017.76.8671. [Epub ahead of print].