Liquid biopsy FAQ

What is liquid biopsy?

Liquid biopsy is a test performed to assess or detect cancer. It involves the collection and analysis of biomarkers from cancer cells in the peripheral blood.

Circulating tumor DNA (ctDNA) is currently the most common source of genetic material used in liquid biopsy analysis, but others including circulating cell-free RNA (cfRNA), circulating tumor cells (CTCs), circulating extracellular vesicles (EVs), tumour-educated platelets (TEPs), proteins, and metabolites may also be used.

When should liquid biopsy be ordered?

Liquid biopsy has three primary clinical uses currently:

• Screen for cancer, specifically colorectal cancer
• Identify potential targeted treatments
• Identify acquired resistance variants that would suggest the cancer will not respond as well to previously effective therapy

This rest of this resource will focus on liquid biopsy for treatment.

Targeted treatment indications

The FDA has approved specific liquid biopsy tests for identifying targeted treatments in solid tumors, including:

In addition to these cancers, liquid biopsy may be used for most clinical indications for which a clinician would consider genomic tumor testing on a solid tumor. Liquid biopsy may identify FDA-approved targeted treatment options as well as investigational treatments.

What are the benefits and limitations of liquid biopsy for solid tumors?

Benefits

• High sensitivity
• Easy sample collection; allows for testing when a solid tumor biopsy is challenging
• Fast turn-around time (~7-10 days)
• Variant detection throughout the tumor as opposed to variants present in a single tumor location
• Low failure rate in the presence of active tumors

Limitations

• May not represent the complete genomic profile of the tumor
• Possibility of false negative based on frequency of variants in the peripheral blood
• Possibility of false positive due to presence of age-related acquired genomic variants in non-cancer cells (clonal hematopoiesis)
• May identify fewer potential targets compared to solid tumor biopsy
• Not ideal for patients with multiple concurrent tumors as the origin of any specific genetic variant is not able to be determined

What are future applications of liquid biopsy?

Research is ongoing to study the effectiveness of different types of liquid biopsy tests in cancer care. Some emerging applications include:

• Diagnosing early stage cancer
• Assessing treatment response
• Monitoring residual disease
• Detecting disease recurrence

Resources & References

College of American Pathologists. The “Liquid” Biopsy. May 22, 2018.

Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet 2019; 20: 71–88.

Jensen K, Konnick EQ, Schweizer MT, Sokolova AO, Grivas P, Cheng, HH et al. Association of Clonal Hematopoiesis in DNA Repair Genes With Prostate Cancer Plasma Cell-free DNA Testing Interference. JAMA Oncol. 2021;7(1):107-110. 

Reed EK, Steinmark L, Seibert DC, Edelman E. Somatic Testing: Implications for Targeted Treatment. Semin Oncol Nurs 2019; 35(1):22-33.

Saarenheimo J, Eigeliene N, Andersen H, Tiirola M, Jekunen A. The Value of Liquid Biopsies for Guiding Therapy Decisions in Non-small Cell Lung Cancer. Front Oncol. 2019;9:129.

U.S. Food & Drug Administration. FDA approves liquid biopsy NGS companion diagnostic test for multiple cancers and biomarkers. 11/9/2020.

About

This resource was developed as part of the Maine Cancer Genomics Initiative (MCGI) and is supported by The Harold Alfond Foundation, Maine Cancer Foundation and The Jackson Laboratory. 

Updated April 2021