Pros and Cons of Liquid Biopsy for Cancer Management

Introduction

In the last decade many new targeted therapies have been approved by the FDA. While many patients now have access to these therapies after DNA-testing of tissue biopsy samples, there are several reasons why some patients may be ineligible for these types of tests and therefore miss the opportunity to benefit from new life-saving therapies. Circumstances for which this may be the case are:

• The tissue is inaccessible due to its anatomical location. This may be true in areas such as such as the mid-lung. Similarly, accessing some areas, such as around major vessels may present a safety risk.
• The tissue material acquired through biopsy is of insufficient quality or quantity for testing.
• The wait time for scheduling the procedure or obtaining the results is too long to impact treatment decisions.

In addition to these circumstances that make tissue biopsy unavailable for DNA testing there are other challenges to the tissue-based approach that are due to the unique aspects of certain cancers. In aggressive or previously treated cancer tissue, biopsies taken at diagnosis often will not reflect the status of the disease at a later time point. Highly precise methods such as needle aspiration may not represent genetic mutations represented throughout the entirety of the tumour. Therefore many providers are looking to liquid biopsy methods to provide options to patients that may fall into these categories.

What is Liquid Biopsy?

A liquid biopsy is an assay that is obtained from body fluid. Several body fluids have been shown to have genetic material derived from tumours such as urine, blood, saliva, stool, and cerebrospinal fluid (CSF). The main advantages of liquid biopsies are:

1. Low risk
2. Minimally invasive
3. Rapid
4. High throughput

The advantages of liquid biopsy make it a well-suited tool for specific applications:

Identify targeted treatments and clinical trial eligibility – For patients for which tissue-based testing is not appropriate or is not available, liquid biopsy can provide a safe alternative test for determining targeted therapy or eligibility for inclusion in clinical trials.

Disease/treatment monitoring – As a rapid, minimally invasive, and economical test, liquid biopsy presents oncologists with real-time information about a tumour. These tests have the potential to provide information on residual tumour cells, treatment efficacy, and early detection of recurrence.

While liquid biopsy has many advantages, there are many two main challenges which prevent this methodology from being deployed more widely. These are:

• Lower sensitivity and precision when compared with tissue.
• Lab specific bias.

Liquid biopsy for cancer is based on the detection of cell-freeDNA (cfDNA) from tumours (ctDNA). In short, cell-free DNAs are small fragments of DNA that are found in bodily fluids (more on cell-free DNAs in our blog post here). In certain cancers tumours shed cfDNAs into the blood which can then be detected by liquid biopsy methods. However, cfDNA specifically from tumours, called, ctDNA are in relatively low concentrations creating a challenging environment for creating both a sensitive and precise test.

While there have been many strides made in the standardization of these methodologies liquid biopsy testing still suffers from a high degree of lab-to-lab variability due to the lack of standardization around procedures and the difficulty in comparing different technology platforms.

Summary

While the challenges related to liquid biopsy present major hurdles to technology vendors, laboratories, and physicians, the desire for liquid biopsy is high among patients who wish to avoid the real risks, potential pain, and high costs that can be associated with tissue biopsy.

Additionally, the opportunity for monitoring treatments and detecting re-occurrence early, along with collecting information across the tumour create present a greater promise for patients to obtain correctly targeted therapies and treat recurrence early.

Back