Dan Norton
Associate Director, Product Management
Personalis, Inc.

Understanding and Evaluating the Latest Advances in Liquid Biopsy Technology

Liquid biopsies are a hot topic in oncology, and for good reason. Some tout them as a relatively painless alternative to operations that can be difficult, expensive, and extremely uncomfortable. While others consider them the future of cancer care, full stop.

But the truth about how liquid biopsies differ from traditional biopsies is actually much more nuanced. There are as many differences between the two approaches as there are similarities and they can be used separately, or in synergy with each other to develop a comprehensive picture of a patient’s molecular profile, essential for making informed treatment decisions.

How Does A Liquid Biopsy Differ From A Traditional Biopsy?

Most people are familiar with the concept of a traditional biopsy: using either local or general anesthesia, clinicians take a physical sample of suspected tumor tissue and then submit the sample for testing. Depending on the location and size of the tumor in question, this process can range from minimally invasive to a disruptive and painful full-scale procedure.

It all comes down to the specifics. While a suspicious mole can be dealt with relatively quickly and painlessly, getting a sample of a brain tumor is another matter entirely. Further, some patients whose conditions have progressed to a serious stage or have been significantly weakened by their cancer may not be strong enough to recover fully from some traditional biopsies.

In dealing with cancer patients of all kinds, doctors need to carefully consider the overall outcome of each test and treatment that they prescribe. Because so many tests and procedures can be maximally invasive or damaging to a patient’s health, doctors need a full array of options so they can weigh the potential positive outcomes of a procedure against the harm that they may do to an already weakened patient.

That’s why, as liquid biopsies have become more advanced, they have become an increasingly important tool in any oncologist’s toolbelt to diagnose and treat various metastatic cancers.

First and foremost: liquid biopsies are not meant to entirely replace traditional biopsies. Instead, they can supplement these procedures and hopefully offer a more complete picture of what is going on in a given patient’s body. By taking a small sample of a patient’s blood, urine, saliva, or spinal fluid, technicians can analyze low concentrations of circulating tumor DNA (ctDNA) that a tumor releases into the patient’s ecosystem.

Most types of liquid biopsies (with the important exception of spinal fluid biopsies) are minimally invasive, and at worst, require a small blood sample to be drawn. This makes them a good way for doctors to keep up with a rapidly metastasizing or changing cancer, when performing multiple traditional biopsies on a hard-to-reach tumor would be too invasive for even the hardiest of patients.

Liquid Biopsy vs. Traditional Biopsy

The reality is, neither type of biopsy will give a doctor the entire picture of an evolving disease, but each can provide important information that may be used to make patient treatment decisions.

When a tumor is easily reachable and the patient agrees to both types of biopsies, these two tests can confirm each other’s results. The overlap, or concordance, in results for both types of tests is often relatively small, with one study finding that only about 10-22% of results matched. Another small study found that only 17% of results matched between liquid and traditional biopsies. However, this doesn’t mean that the tests in question were inaccurate. Instead, it demonstrates the importance of getting the clearest picture possible with the biopsy and testing options available to a specific patient.

While technologies to interrogate liquid biopsy specimens continue to evolve, traditional biopsies may still provide more accurate results. One study found that tissue biopsies found “relevant gene variants in 87% of instances, compared to 25% found by liquid biopsies”. But traditional biopsies don’t always show the entire picture of a single tumor, as tumors are often heterogeneous.

Due to improvements in sequencing technologies, the assays used to analyze both types of biopsies rarely produce false positive results, meaning that doctors can confidently base treatment decisions on most positive results. Liquid and traditional biopsies essentially source their data from related, but entirely separate sources, which accounts for the variability of what each can detect in any given situation.

Liquid biopsies can pick up on traces of ctDNA from different parts of the patient’s primary tumor, or from entirely different tumors that may be metastasizing in other parts of the patient’s body. This means that they can sometimes produce unanticipated results that may steer further testing and treatment in a direction that the medical team may not have originally expected.

In addition to this, it’s important to understand how tumors change over time, requiring shifts in treatment and detection plans as the disease evolves. Relying only on possibly out-of-date information from an early, pre-treatment biopsy because a patient may be seriously harmed by a second traditional biopsy is not an optimal situation. Liquid biopsies can be used to keep current as cancer evolves, particularly in fragile, unwell, or elderly patients.

Liquid biopsies may also fit into an overall treatment plan as minimally invasive post-remission check-ins. Depending on the type of cancer a patient has dealt with in the past, a doctor can order easy liquid biopsy tests to ensure that the medical team will know quickly if disease recurs, or a certain malignant mutation comes back.

Recent Advances in Liquid Biopsy

The science surrounding liquid biopsy is evolving rapidly as organizations work to develop less invasive and more sensitive tests that can tell us more about malignancies. Personalis® is committed to creating liquid biopsy tests that push the boundaries of what can be accomplished in this promising field, while also making sure that patients are up-to-date about the changing capabilities of our tests.

NeXT Personal™ is empowering the field to move beyond existing molecular residual disease detection tools to allow for ultra-sensitive disease recurrence detection, in earlier stages, with greater control over customized variant tracking. NeXT Liquid Biopsy™ improves upon older tests by sequencing approximately 20,000 genes from ctDNA, and acting as an important complement to our traditional ImmunoID NeXT® tumor biopsy. Taken together, these two tests can provide a comprehensive picture of a cancer’s mutational landscape by attacking the problem from both sides.

The most important thing to understand about liquid and traditional biopsies is that both can be essential tools for diagnosing and treating a patient’s cancer. Each case is different, and doctors may recommend different combinations of tests at different points in a patient’s treatment cycle. But there’s no question that liquid biopsy testing is a field that we’re very excited to continue working in, and one that will likely produce even less invasive and more comprehensive results in the future.

Contact us to learn more about NeXT Personal and NeXT Liquid Biopsy.


All products described here are for Research Use Only and not for use in diagnostic procedures (except as specifically noted).