Which is more accurate in detecting cancer; a tissue biopsy, in which a small piece of cancerous tissue is cut out and examined under a microscope, or a liquid biopsy, in which body fluids such as blood or urine are used to find fragments of cancer cells in the DNA and analyzed by genetic testing?

Also, tissue tests are often considered the most accurate and final cancer diagnostic test. Is it true, however?

“Maybe or maybe not,” said Dr. Kim Tae-you, chairman of the Korean Cancer Association and a professor of oncology at Seoul National University Hospital, on the YouTube channel, “I am a doctor.”

“Cancer does not necessarily exist in one part. If you take a lung cancer biopsy, it only has information about that tissue.”

If a patient has lung cancer in both lungs and the cancer has metastasized to the liver and bones, a biopsy taken from one lung cannot give a complete picture of the cancer, an accumulation of genetic mutations, Kim explained.

“Cancer has different gene mutations in different parts of the body, so in principle, if the cancer is in four or five places, you need to take a separate tissue test to look at the gene mutations, which is technically difficult,” Professor Kim said. “However, if you test with blood, the information from all five places comes out, and many studies show that liquid biopsies are more accurate than tissue tests.”

Liquid biopsies are also an important testing option for cancer patients who can't have a biopsy. Cancer must eventually be confirmed by biopsy, which is difficult when the cancer is located deep in areas difficult to access through surgery or other procedures. These patients account for not a small percentage of all cancer patients.

“If the cancer is deep in the body, we can't even do a biopsy. About 30 percent of all cancer patients are difficult to biopsy,” Kim said, pointing out that liquid biopsy is an effective way to check various information about cancer in patients who cannot be biopsied.

So, how can liquid biopsy through body fluids, such as blood and urine, provide adequate information about cancer in the body?

“Cancer cells have DNA genes. Every cell has a DNA gene that flows out. If it flows out into the blood, you can see the gene mutation that comes out of the cell using blood, urine, or any fluid in the body without taking a biopsy,” Kim said, explaining this is the principle of liquid biopsy.

What can liquid biopsies tell us about cancer?

“Liquid biopsies detect genetic mutations in the blood that shouldn't be there,” Professor Kim said. “Then, the technology is available to estimate whether it is lung cancer, breast cancer, or the primary site.”

That, in turn, explains why technology development in multi-cancer screening using liquid biopsy is very active at home and abroad.

“Cancer screening can diagnose less than 50 percent of all cancers. The main reason this field is still developing is that there are still various limitations in existing screening tests and liquid biopsy can help to overcome them. If we use it well combined with existing screening tests, we can make cancer screening much more efficient than now.”

Liquid biopsy can provide more information about cancer than NGS (Next Generation Sequencing) testing.

“Liquid biopsy can get information on DNA, RNA, and protein,” Kim said, distinguishing that “liquid biopsy is bigger, and NGS is a technology that can highly analyze DNA among them.”

Liquid biopsy does not necessarily mean NGS testing. “It depends on what the target is,” Kim said. “DNA and RNA can be analyzed through NGS.”

Liquid biopsies are now almost available in hospitals where tissue tests are performed. While foreign products used to cost 3 million to 4 million won ($2,168 to $2,891), domestic products are now available, making them much cheaper than before. “There are advantages to using Korean products because they are covered and the price is much lower,” Kim said.

However, not all cancer patients are covered by insurance for liquid biopsy. “Korean regulations currently allow NGS testing twice a lifetime as a screening benefit for stage 3 or 4 advanced cancers,” Kim noted. “From December 2023, the co-payment was 50 percent but it changed to 80 percent for other cancers while remaining at 50 percent only for adenocarcinoma of lung cancer.”

Why did the percentage of screening benefits for NGS tests considered essential for patients with advanced cancer increase?

“The Health Insurance Review and Assessment Service panels concluded that the clinical utility was not that great,” Kim said. “However, there was no input from clinicians but a lot of input from the review panels and the Ministry of Health and Welfare, which wanted to reduce costs.

Furthermore, except for patients with stage 3 or 4 advanced cancer, other cancer patients are systematically prevented even from paying out-of-pocket for NGS testing in Korea.

“It's a discretionary non-reimbursement test, so they don't allow it now in principle,” Kim said. “One can say, 'I have cancer and I'm going to pay for the exact test with my money, so why are you stopping me, why are you prohibiting it?’” This is something that I would like to talk to the government and improve.”

Fortunately, cancer screening through liquid biopsy is now available at some health screening centers.

“Some health screening centers still offer the test. You have only to ask the health screening center, saying, 'Let's try cancer screening with blood,'” Kim said, adding that liquid biopsy is useful for older adults who need to undergo multiple tests to screen for cancer.