Can lung cancer be diagnosed with just a blood test? Yes, thanks to liquid biopsy.

Liquid biopsy is gaining traction as a diagnostic method for cancer. Lung cancer is no exception.

A liquid biopsy refers to the analysis of cancer cell fragments (ctDNA), cancer cells themselves (CTC), exosomes, and other components present in bodily fluids, such as blood, urine, or cerebrospinal fluid, to confirm the presence, type, and genetic mutations of cancer for use in diagnosis and treatment.

So, what is the current reality of liquid biopsy in the field of lung cancer diagnosis and treatment?

“Lung cancer was previously diagnosed through tissue biopsy. However, thanks to recent advancements in lung cancer diagnostic technology, cases of diagnosing lung cancer using liquid biopsy are increasing nowadays,” said Professor Park Seong-yong of the Department of Cardiovascular and Thoracic Surgery at Samsung Medical Center, while explaining the changing reality of lung cancer diagnosis and treatment in the medical field on the Korean Association for Lung Cancer's YouTube channel,” Ask Anything About Lung Cancer.”

How is liquid biopsy currently utilized in the field of lung cancer diagnosis? Has it reached a level where it can completely replace “solid biopsy”—the tissue biopsy performed through surgery, bronchoscopy, or needle insertion? No. Tissue biopsy is still considered the most reliable method for diagnosing lung cancer, and liquid biopsy currently plays a “complementary role,” filling gaps that tissue biopsy cannot address.

Professor Kim Ju-sang of the Department of Pulmonology and Critical Care Medicine at the Catholic University of Korea Incheon St. Mary's Hospital pointed out its limitations.

“From a physician's perspective, the best method for lung cancer diagnosis is direct solid biopsy. It provides the most accurate and abundant information for directly locating and diagnosing the lesion site. However, solid biopsy is physically very difficult to repeat when the cancer worsens or improves during treatment, and patients also find it challenging,” Professor Kim said.

In such cases, when estimating whether a patient who initially showed cancer cells or cancer-specific mutations in their blood has worsened or improved after treatment, liquid biopsy becomes very useful. It allows us to indirectly determine whether amelioration or aggravation has occurred when such markers disappear or improve, Kim explained. He added that liquid biopsy and solid biopsy are currently used complementarily in clinical practice.

So, why can't a liquid biopsy replace a solid biopsy?

“Because liquid biopsy alone is highly insufficient for diagnosing disease. While it might be possible in very advanced stages, in early stages, there may be a few circulating cancer cells in the blood. Theoretically, they circulate from the very beginning, but if the quantity is too small, diagnosis becomes impossible,” Professor Kim explained, pointing out its limitations.

“Cancer cells can have 10 different forms, but only one might circulate in the blood. So, it doesn't show the whole picture of the cancer, just a partial one,” Kim said. “Just because something isn't seen in a liquid biopsy doesn't mean there's no cancer, and seeing a lot doesn't necessarily mean the disease is severe. Currently, this is a test method that requires very close consultation with medical professionals.”

For instance, if a mass is visible in the lungs on an imaging test like a chest CT scan, one cannot currently be certain it is not cancer just because it is not detected in a liquid biopsy. Professor Kim explained that cancer cells themselves are highly heterogeneous. A single person doesn't have identical cancer cells; instead, there are hundreds of types, hundreds of millions of cancer cells. Some individuals have a tendency to circulate, while others tend to cluster in one place.

“The cancer visible before our eyes is localized, while the circulating cancer is something else entirely. It's a misconception to say that just because the visible cancer is present and the circulating cancer isn't, the visible one isn't cancer,” he said. “Patients initially diagnosed as early-stage via imaging might have their diagnosis questioned – ‘Is it truly early-stage?’ – if they had undergone a liquid biopsy.”

How is liquid biopsy currently used, then?

“There are patients where the disease has spread extensively throughout the body, yet tissue biopsy or surgery is impossible. For such patients, if we can detect specific mutations or cancer cells through their blood, we can apply the latest treatment methods, including various targeted anticancer drugs recently used,” Professor Kim said, adding that liquid biopsy is applied to patients ineligible for solid biopsy to find treatment options.

The current liquid biopsy method available for lung cancer utilizes blood tests. Other methods using bodily fluids, such as urine, are currently under research. Additionally, if lung cancer causes disease in the pleura, pleural fluid may accumulate; liquid biopsy using this fluid is also being researched. Recently, research is also been conducted on diagnostic methods using bronchoscopy washout fluid.

Furthermore, tests that detect DNA from cancer cell fragments in the blood are currently commercially available in medical settings, and some of these liquid biopsy methods are covered by insurance.

“In cases where lung cancer is located in areas where a tissue biopsy is too risky or could cause complications, and where there is strong suspicion but diagnosis is not straightforward, even if the liquid biopsy is an unreimbursed test, we tend to proceed with the test after thorough discussion with the patients,” Professor Kim explained.