When Tests Collide: Perspectives on Liquid vs. Tissue Biopsies

By Tiffany Parnell
Saturday, July 1, 2017

As liquid biopsies inch closer to becoming a standard of care, questions about their efficacy, use and role in cancer diagnosis and treatment abound. Discordant research findings between liquid and tissue biopsies only add to the confusion.

A molecular diagnostic tool, liquid biopsies enable physicians to search for anomalies within a malignant tumor’s genome. The goal of such analysis is to identify genomic alterations within a tumor that physicians can target with specific therapies.

Liquid Biopsy under the Microscope

Liquid biopsies differ from tissue biopsies in that they are not used to diagnose cancer. Rather, they provide information about the cell-free tumor DNA circulating in a patient’s blood serum. By looking for specific genomic alterations, or molecular targets, within that tumor DNA, physicians can better determine which treatments hold the most promise for treating patients’ individual tumors.

“I think there will be a day that we’ll all be using liquid biopsies more routinely, even perhaps in certain cases, instead of tissue biopsies — not necessarily to diagnose cancer, but to perform molecular diagnostics in patients who are already known to have cancer ... . No. 1, it’s going to be safer and cheaper if tissue biopsy can be avoided, and No. 2, it’s going to be much more reliable than it is today. But I’m not particularly ready at this point to just test all patients with liquid biopsies because I’m not convinced it correlates completely with tissue biopsies.”
— Sibel Blau, MD, hematologist/oncologist and Medical Director at Rainier Division of Northwest Medical Specialties

The premise behind liquid cancer biopsies is not new — physicians have traditionally derived similar information about the tumor genome by performing next-generation sequencing on tissue biopsy samples. At present, tissue biopsy remains the gold standard for cancer diagnosis and evaluation. Because of the noninvasive nature of blood-based liquid cancer biopsies, however, there are cases in which liquid biopsy may offer an advantage.

“Some tumors are located in places that are difficult, dangerous or risky to biopsy [via needle or surgery],” says Shoshannah Roth, PhD, Manager of Health Technology Assessment Information Services at the Pennsylvania-based ECRI Institute. “Also, in patients with metastatic cancer, it’s somewhat impractical to biopsy all of the different tumor seeds around the body. ... Another advantage is that since these tests are typically noninvasive — you’re looking at a blood or maybe a urine sample — it can reduce patient anxiety because they don’t have to undergo a painful test.”

So far, one liquid biopsy test has received FDA approval. The blood-based test is indicated for patients with non-small cell lung cancer and is designed to detect epidermal growth factor receptor gene mutations in tumors.

“Lung cancer is where we have the most targeted therapy options, but getting enough tissue to run molecular assays has become an issue,” says Young Kwang Chae, MD, MPH, MBA, Assistant Professor of Medicine, Division of Hematology/Oncology at Northwestern University’s Feinberg School of Medicine.

One of the lung cancer-related challenges physicians face is tissue necrosis, which can hamper their ability to collect sufficient tumor cells for molecular analysis.

“That’s where the blood assay becomes much more useful,” Dr. Chae says. “And sometimes, [in cases of] progression of disease where we’re looking for emergence of mutations, it’s this noninvasive approach that might save a patient from having an invasive biopsy.”

That said, liquid cancer biopsy has limitations.

“We haven’t yet determined the best time to perform a liquid biopsy test,” Roth says. “We know the DNA circulating in these liquids might change over the course of the disease, and we don’t know how that influences the test results at this time. Related to that, some early studies have already reported some conflicting results between traditional tissue biopsy genetic analysis and the liquid biopsy genetic analysis, so we need to learn more about that and how that might impact patients.”

Complement or Competitor?

Research funded by Guardant Health, the manufacturer of a liquid cancer biopsy test known as Guardant360, evaluated nearly 400 patients for whom both liquid cancer biopsy and tissue biopsy results were available. Overall accuracy of the liquid biopsy in comparison with tissue biopsy was 87 percent, according to the National Cancer Institute. Other studies in which researchers performed both liquid cancer biopsy and tissue biopsy in the same patients, however, found lower levels of concordance. Sibel Blau, MD, hematologist/oncologist and Medical Director at Rainier Division of Northwest Medical Specialties, based in Washington state, believes divergence is to be expected.

“This is not uncommon when you actually look at different companies and different commercial labs,” says Dr. Blau, whose JAMA Oncology-published study found great discrepancies between liquid cancer and tissue biopsy results. “... [E]ven with tissue, [you may have] discrepancies within the results because the way that [labs] do testing may be different. The liquid biopsy looks at very different aspects of testing. It’s looking at the DNA that has been shed into the bloodstream.”

“We need to educate ourselves that these two are really different tests,” Dr. Chae adds. “In the future, they will most likely complement each other.”