Liquid Biopsy

Liquid biopsies may be used to help guide treatment, predict treatment response or prognosis, and monitor therapy and disease progression in select cancers.

There are currently two main types of clinically available liquid biopsy:

• Circulating tumor cell count (CTC)—these tests look at whole tumor cells in the blood to help determine prognosis in breast, colon, or prostate cancer that has spread to nearby or distant organs (metastatic). They may also be used to evaluate responses to therapy for those cancers.
• Circulating tumor DNA (ctDNA)—these tests look for tumor DNA that cancer cells release into the blood. An example is an FDA-approved test that is used to decide if anti-EGFR medications (erlotinib or osimertinib) can be used to treat non-small-cell lung cancer.

Testing may be ordered:

• When you have metastatic breast, colon, or prostate cancer and a better understanding of the prognosis (predicted course of disease) is necessary to guide treatment
• When monitoring response to treatment for metastatic breast, colon, or prostate cancer
• Before or after starting certain specific targeted therapies for non-small cell lung cancer

• Circulating tumor cell count (CTC)—circulating tumor cell counts are measured as the number of CTCs in a specified volume of blood. Results may be interpreted as favorable or unfavorable. Prostate, colon, and breast cancers all have unique cutoffs for when a CTC count is no longer favorable for prognosis.

  Studies show that lower CTC counts or levels are associated with a more favorable prognosis, specifically how long individuals live after treatment (overall survival) and the time between diagnosis and progression of the disease to a higher stage or recurrence of the tumor (progression-free survival). If the CTC count is above a certain cutoff during the course of cancer, it is associated with a poor prognosis and is predictive of shorter progression-free survival and overall survival. If it is below that cutoff it is associated with more favorable prognosis.

• Circulating tumor DNA (ctDNA) tests—these tests can detect mutations in the tumor that can predict potential responsiveness or resistance to certain therapies. For example:
  • In a person with lung cancer, a positive ctDNA test for a sensitizing EGFR mutation (i.e., a mutation that makes the cancer sensitive to targeted therapy) means the cancer is likely to respond to targeted therapy and the individual can receive these treatments. However, ctDNA testing is known to sometimes give false-negative results (meaning the mutation is present but not detected by the ctDNA testing). For this reason, the FDA recommends a tissue biopsy if the liquid biopsy is negative (doesn't detect a sensitizing mutation).
  • In addition, when a patient has already been treated with an EGFR-targeted tyrosine kinase inhibitor but does not appear to be responding favorably to the treatment, a liquid biopsy may be used to detect an EGFR T790M mutation, which causes resistance to targeted therapy. If an EGFR T790M mutation is detected, it can then be targeted with a different drug that has been designed especially for this particular mutation. However, data are currently limited on this use for a liquid biopsy, so it may be used only if a tissue biopsy cannot be obtained.

Liquid biopsies are currently clinically available for only a few cancer types. These include metastatic breast, colon and prostate cancers, and non-small cell lung cancer.

While liquid biopsies continue to become commercially available and in some cases are FDA-approved, more research is needed to understand the benefits and limitations of these tests. For example, it is still unclear if using liquid biopsies to guide treatment actually improves outcomes for people with cancer.

Liquid biopsies are currently most useful in detecting mutations that predict response or resistance to treatment in lung cancer and for evaluating prognosis in select cancers. Over time, these tests may become a part of management of a wider array of cancers. Liquid biopsies are also showing promise as cancer screening tools in research settings, but none are currently FDA-approved as screening tests.

Some experts say that more research is needed before liquid biopsies are used in medical practice. In March 2018, a review jointly published by the American Society of Clinical Oncology and the College of American Pathologists concluded that currently, cell-free tumor DNA tests are not useful outside of clinical trials. The groups say that prospective studies are needed to evaluate how well liquid biopsies perform in diagnosing cancer, but such studies have not yet been conducted. The experts acknowledge, however, that research on these tests is progressing quickly and use of liquid biopsies will likely evolve in the near future.

For diagnosis of your tumor, you will need a conventional tissue biopsy. As mentioned above, if your liquid biopsy is negative for certain mutations, you may need to have follow-up testing done on a conventional biopsy specimen. A liquid biopsy may miss details available from a conventional tissue biopsy and can't determine where in one's body a mutation has arisen.

In some situations, a liquid biopsy alone can provide sufficient information for making treatment decisions. It may be sufficient if, for example, the primary test is positive for a mutation or if a T790M mutation is detected and a tissue biopsy cannot be obtained. While liquid biopsies are promising and powerful tools, they complement but do not necessarily replace tissue biopsies for the foreseeable future.