Utility of Liquid Biopsy for a Cancer Patient

Highlights

Liquid biopsy is the test that isolates and analyzes circulating tumor DNA from blood or urine samples through sequencing, and can provide information on potentially actionable genetic mutations and aberrations linked to the cancer. While this technique has benefits for easy monitoring of the disease, it has the potential for false positives and currently lacks standardization in sample collection and analysis.

When a person is diagnosed with cancer, one of the tests is a tissue biopsy for solid tumors and bone marrow biopsy for blood cancers, both invasive procedures that could be done via a needle, endoscopy or surgery, and in some that may not even be possible if the location of the tumor is inaccessible. The results of examining the cells from these biopsies provides details on the type, stage and prognosis of the cancer. In more recent times and with advancing technologies, scientists have been able to detect circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in blood, urine and saliva samples. A liquid biopsy is therefore sampling of a patients’ blood or other easily and non-invasively accessible samples for diagnostic, prognostic and monitoring purposes.

Liquid biopsy is based on the premise that the rapidly growing cancer cells in the body release their DNA into the blood. There are techniques to identify and extract the minuscule amounts of ctDNA from the high background of normal circulating DNA in the blood or urine. Probing and analyzing this ctDNA through various assays including sequencing, can provide information about the genetic characteristics of the tumor. Identification of genetic modifications such as cancer related gene mutations, other chromosomal changes such as amplifications, deletions, inversions, translocations of segments impacting cancer genes, gives insight into the molecular characteristics of the cancer – valuable and potentially actionable information for personalization of type and course of treatment (Elazezy and Joosse, Comput Struct Biotechnol J., 2018).

What are the Advantages and Disadvantages of Liquid Biopsy?

Advantages of liquid biopsy in Cancer

Listed below are some of the key advantages of doing liquid biopsy in cancer.

• Can be done on samples such as blood that are easily accessible and routinely used for laboratory tests. It is not dependent on painful, invasive and expensive procedures as needed for tissue or bone marrow biopsy.
• Allows monitoring of response to treatment by assessing the levels of the ctDNA.
• Allows monitoring of recurrence of disease by doing periodic analysis of levels and characteristics of ctDNA once the patient has completed treatment and is in remission. This monitoring is also called assessment of minimal residual disease (MRD).
• For metastatic or progressive disease, the monitoring via liquid biopsy of the ctDNA will give insight into how the tumor has evolved from its primary characteristics and can help with change in treatment strategies to treat the evolving and aggressive cancer.

Disadvantages of liquid biopsy

Some of the disadvantages of liquid biopsy include:

• The circulating tumor DNA (ctDNA) concentration can be extremely low in a high background of normal circulating DNA and therefore the liquid biopsy approach can miss detection and therefore report false negative results.
• With the techniques used for liquid biopsy where minuscule amounts of ctDNA are amplified for analysis, the possibility of errors and artifacts resulting in false positive results is high.
• Liquid biopsy techniques and workflows today lack standardization in sample collection and sample analysis.
• Due to differing amounts of sample between tissue biopsy and liquid biopsy, they may provide non-overlapping and different information for the same individual which may confound the treatment choices.

A study by a British Columbia group found that ctDNA provided additional useful information to a prostate biopsy in men newly diagnosed with metastatic castration sensitive prostate cancer, and they also confirmed that there was an 80% overlap in mutations between ctDNA and prostate tissue biopsy. The optimal approach as per their study suggested the use of both the tissue and liquid biopsy as neither approach by itself captured all the genetic details in all patients (Vandekerkhove G, et al, Eur Urol, 2019). Another study from MD Anderson, Texas, also highlighted the utility of liquid biopsy and ctDNA analysis in pancreatic cancer (Bernard V, et al, Gastroenterol., 2019). In summary, liquid biopsy has the potential to provide useful information during different stages of cancer treatment and for monitoring during and after treatment phases.

For the cancer patients interested in pursuing liquid biopsy test, there are many companies established in this field. The liquid biopsy tests vary based on the cancer type and list of genes covered, the depth of sequencing coverage of the genes and the sensitivity and specificity of the assays. In the US, companies such as Guardant Health, Foundation Medicine, Genomic Health and many others offer different liquid biopsy tests. Multiple companies in India also do liquid biopsy tests including MedGenome, Dr Lal Path Labs, Strand Life Sciences, Datar Cancer Genetics, Redcliffe Life Sciences and others. Liquid biopsy tests are mostly out of pocket expenses for the patient that are not covered by their health insurance.

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