Liquid biopsies, or blood tests that identify the genetic makeup of cancerous tumors, could soon help guide patients to personalized treatment options faster. The tests open up a new realm of cheap, non-invasive early cancer detection options. Unfortunately, not all liquid biopsies are created equal, and many questions need to be answered before they become part of the standard of care for many tumor types.
Some large tumors shed millions of cells into the bloodstream every day. These circulating tumor cells (CTCs) play a crucial role in cancer metastases. And while researchers have known about these rogue cells for over a hundred years, finding and measuring them has been difficult until very recently. Now, with advances in technology, physicians can draw a patient’s blood, isolate the CTCs, and speedily sequence the genetic material found in them to diagnose cancer.
More recently, researchers have also started focusing on scanning blood samples for fragments of tumor DNA that originate directly from tumors or from CTCs. Since these circulating tumor DNA (ctDNA) fragments are often easier to isolate and analyze, they have led to an explosion in liquid biopsy research. For example, using ctDNA can help doctors track slight changes in tumors and determine the most effective cancer therapy for a patient at each stage of his or her disease.
The FDA approved the first liquid biopsy test in 2016, specifically for use in patients already known to have non-small cell lung cancer. The test picked up alterations in the epidermal growth factor receptor (EGFR) gene that could affect how patients responded to one type of targeted therapy. With more tests now approved, researchers from Johns Hopkins recently decided to compare two commercially available liquid biopsy tests to see if they returned similar outcomes.
But the researchers found significant differences between the results when they sent identical data from metastatic prostate cancer patients to the two test providers. The Guardant360 test from Guardant Health sequenced coding segments of 73 genes, and the PlasmaSELECT panel from Personal Genome Diagnostics sequenced coding segments of 64 genes. But even when researchers compared results from overlapping genes, only 7.5 percent of the cases (three out of 40 patients) completely matched for all the mutations reported.
“Liquid biopsy is a promising technology with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve,” says Gonzalo Torga, a prostate cancer researcher who was one of the authors of the study, in a statement. “We can’t tell from these studies which laboratory’s panel is better, but we can say that certification for these laboratories must improve.”
The results, published in the journal JAMA Oncology in December, are important despite the small sample size: Different results could mean doctors prescribe different treatment plans. In the case of metastatic prostate cancer, this could mean life or death for patients.
“We have so many of these assays now, and it is important to ultimately compare them and come up with standards that we can be sure that an assay is high quality,” says Maximillian Diehn, an assistant professor of radiation oncology at Stanford University.
Most experts agree that liquid biopsies won’t completely replace tissue biopsies — at least not yet. Many tumor types don’t have specific, reliable biomarkers that can be picked up in liquid biopsies, especially in early stages of the disease. Additionally, when distributing something like a blood test to a wide range of healthy people, doctors also have to worry about the potential for false positives. An incorrect cancer diagnosis could cause unnecessary patient stress and wasted resources spent on additional tests when the patient may not even have cancer.
But scientists are moving towards more accurate and earlier cancer detection tests. In a study published in the journal Science last month, an international team of researchers described a new liquid biopsy test that not only screens for DNA alterations associated with tumors but also proteins from eight major types of cancer: lung, breast, colon, pancreas, liver, stomach, ovary, and esophagus. In more than 1,000 people already diagnosed with these cancer types, the test correctly detected disease about 70 percent of the time. The test was more accurate in detecting later stage cancers, with a 78 percent success rate in stage III versus 43 percent success in stage I tumors. But even in 812 people without cancer diagnoses, the test found false positives in less than 1 percent (or just seven people).
And liquid biopsies can be still very useful for patients who have already been diagnosed with cancer. Studies have shown that detecting ctDNA in the blood after cancer treatments can predict the recurrence of the disease. Instead of costly, time-consuming imaging scans every couple of months, liquid biopsies could allow doctors to catch cancer recurrence quicker, delivering treatments at a critical time.
“One of the very exciting things about these technologies is that you could really envision using liquid biopsy approaches really at almost any point in the patient’s care continuum: All the way from early detection to resistant and very advanced disease and everything in between,” Diehn says. “That’s very exciting, but it’s also a challenge because we really have to decide where to focus our efforts first and where is this going to be most high yield.”