Despite the terminology “liquid biopsies” (LBx) becoming common place in diagnostic lexicon, as a routine clinical technology, LBx is still very much in its infancy. Liquid biopsy has a broad definition with a narrow connotation. Generally speaking, LBx is testing of biofluids including blood, urine, saliva and cerebral spinal fluid in lieu of more conventional (tissue) biopsies or assessment (imaging) approaches. In reality, mention of LBx recalls blood or plasma based testing. More specifically circulating tumor DNA (ctDNA), and to a lesser extent, circulating tumor cell (CTC) testing.
Benefits of liquid biopsy testing include:
- Minimally invasive – A blood draw would be attainable in those patients who are unable to undergo tissue biopsy due to health risks of an invasive biopsy procedure.
- Tumor site agnostic – tissue biopsies are limited to sampling site while LBx can inform on all (metastatic) tumor sites
- Real time profiling – archival tissue biopsies can be years old and vaguely representative of the patient’s current tumor. ctDNA has a half-life of hours and can be sampled repeatedly to give a more current mutational profile.
- Faster lab results – LBx averages about 2 weeks quicker results versus tissue testing
- Earlier detection of recurrence – In some settings, LBx can detect recurrence weeks to months before conventional imaging approaches.
The first approved ctDNA LBx assay was in 2016 with Roche’s Cobas EGFR Mutation Test V2. Since then we’ve seen three more approvals consisting of qPCR and NGS covering both centralized and decentralized CDx models, thereby firmly paving pathways for ctDNA LBx as a CDx technology.
- There are many more lessons to be learned as the field of LBx evolves but some key take away’s and trends currently are:
- LBx will not replace tissue. It’s not a 1 for 1, but rather complementary tools.
- LBx has quickly leaped from qPCR into NGS. As the field of molecular testing is moving away from single target platforms, future LBx approvals will likely all be NGS based.
- In addition to LBx for therapy guidance, we expect to see LBx advancing diagnostic applications such as treatment and surveillance monitoring. There is a trend for personalized NGS assays which touts extremely high sensitivity.
- More clinical data on LBx in different disease settings will be critical to understand where LBx can and should be applied as well as drive adoption.
- There is an urgent need for standardization across LBx assays. Qualified standards, controls and QC materials are being developed and marketed. These will help to support analytical validation studies such as limit of detection.
- Growth of LBx in global markets may be slower due to technology hurdles coupled with the risk of sample stability during international transit.
What is evident is that the momentum and fervor for the LBx field is accelerating. We see more dedicated LBx conferences, seminar tracks, and at NeoGenomics’, projects including a LBx component are becoming more common. But with all of the excitement, there is still much more work that is needed for liquid biopsies to be broadly accepted into routine practice.
