Benefits

The clinical utility of liquid biopsy is reinforced by numerous other advantages including:

• Ease of collection

• Low risk of adverse effects

• Ability to perform serial testing, which is useful in clinical trials

• Potential to assess the whole-body impact of disease and response to therapy

• Potentially lower cost of diagnostic testing and much faster turnaround time for results than tissue biopsies, which can then accelerate interventions

The potential applications of liquid biopsies include:

• Screening for presence of disease

• Patient stratification and therapy selection

• Monitoring treatment response and drug resistance

• Detection of minimal residual disease (MRD) after surgery / recurrence

Also, regulatory approval progress has been slowly advancing for liquid biopsies. In 2020, the FDA approved two comprehensive genomic profiling liquid biopsy tests . . . the Guardant360 CDx which detects changes in 60 different genes, and the FoundationOne Liquid CDx which can identify mutations or alterations in 300 genes as well as help determine tumor mutation burden and microsatellite instability, key indicators for potential immunotherapy response.

Limitations

The first limitation of liquid biopsies in clinical applications is the lack of being a proven “gold standard” that tissue biopsies have long been. To prove their utility, interventional clinical trials are needed. Liquid biopsies still carry the risk for false-positive or false-negative results, prompting the FDA to recommend confirmation of a negative result from the Guardant360 CDx and the FoundationOne Liquid CDx with a tissue biopsy test.

Next, while the FDA has approved liquid biopsies for people with certain advanced cancers to help guide therapy decisions and detect earlier the recurrence of disease, it remains to be seen if cancer screening of the general population is beneficial. The argument is that earlier detection of cancer is only valuable if there are available effective therapies or interventions that can be started earlier to help patients. Otherwise, the result could be people living longer knowing they have an incurable disease. H. Gilbert Welch from the Center for Surgery and Public Health at Brigham & Women’s Hospital states that “I want to know if multi cancer liquid biopsy screening of the general population will help people live longer.”

Conclusion

Liquid biopsies will continue to evolve in the application of precision medicine to cancer detection, diagnosis, and treatment. They have enormous advantages of being non-invasive, low cost, and better able to detect the heterogeneity of cancer. However, the extent to which they can replace standard tissue biopsies is unclear.

References

• “There’s a New Frontier in Detecting Cancer: Blood Tests”; Jonathan Saltzman; Boston Globe; January 26, 20022

• "Liquid Biopsy: From Discovery to Clinical Application”; Catherine Alix-Panabieres and Klaus Pantel; American Association for Cancer Research Journal; April 3, 2021

• “The Future of Liquid Biopsy”; Catherine Alix-Panabieres; Nature; March 26, 2020

• “ctDNA Assays: Exploring Their Clinical Use in Oncology Care” Pashtoon Kasi; ASCO Daily News; January 13, 2022

• “Precision Oncology: Advancing the Development of Liquid Biopsy-Based Diagnostics with NGS”; Rob Fannon; Onco’Zine; November 16, 2021

• "Liquid Biopsy: Misplaced Faith in Early Cancer Detection?”; H. Gilbert Welch; STAT News; August 31, 2021

• “The Evolution of Liquid Biopsy in Cancer Care”; Jo Cavallo; The ASCO Post; October 10, 2021