One of the biggest worries after liver cancer treatment is whether the cancer will come back. Even when a tumor is successfully treated or removed, doctors need to watch closely to be sure the cancer does not return. This is known as cancer recurrence, which means that cancer cells that were too small to detect may remain in the body after treatment and later grow into new tumors. Recurrence can happen in the liver or, less commonly, in other parts of the body. Because of this risk, regular follow-up appointments, imaging tests, and blood work are important to help detect any recurrence as early as possible, when additional treatment options may be most effective.
Researchers are studying whether a simple blood test could help find signs of cancer earlier than scans can. This type of test is called a liquid biopsy.
What is a liquid biopsy?
A liquid biopsy is a blood test that looks for tiny pieces of DNA released by cancer cells into the bloodstream. These pieces are called circulating tumor DNA (ctDNA). After treatment, ctDNA may provide clues that cancer cells are still in the body, even if they cannot yet be seen on a CT scan or MRI. Unlike a traditional biopsy, which requires taking a tissue sample from a tumor, a liquid biopsy only requires a blood sample. It is less invasive and a quicker way to check if the cancer has returned.
What can this blood test tell us?
Sometimes, after surgery or other treatments, a very small number of cancer cells can remain in the body. These cells may be too small to show up on imaging tests. Researchers call this minimal residual disease, which simply means a small amount of cancer may still be present after treatment. Researchers are studying whether ctDNA testing can help identify people who have a higher chance of their liver cancer returning.
In a 2023 study, researchers tested the blood of 20 people who had surgery for hepatocellular carcinoma (HCC), the most common type of liver cancer. All six people who had a positive ctDNA test after surgery experienced an early recurrence of their cancer. However, cancer also returned in two people whose ctDNA tests were negative.
While these results are promising, the study was small. A negative test result did not guarantee that the cancer would not come back and larger studies are needed to learn how accurate and reliable this test may be.
How could this help patients in the future?
Today, doctors look for liver cancer recurrence using imaging tests such as CT scans and MRIs, along with blood tests like alpha-fetoprotein (AFP). AFP is a substance that can be higher in some people with liver cancer, so doctors may use it along with imaging to watch for signs that the cancer has returned.
Researchers believe ctDNA testing could one day be used alongside these tools to help doctors:
- Identify people who may be at higher risk for recurrence;
- Monitor patients more closely after treatment;
- Check for possible signs of recurrence sooner
- Personalize follow-up care based on an individual’s risk.
ctDNA testing is an exciting area of liver cancer research. It may help doctors identify patients who are at higher risk of recurrence and could improve how people are monitored after treatment.
However, these tests are still being studied and are not yet a replacement for regular scans and follow-up care. For now, ctDNA testing should be viewed as a promising tool that may one day help doctors detect liver cancer recurrence earlier and provide more personalized care for patients.
References:
Xu, Y., Cai, J., Zhong, K., Wen, Y., Cai, L., He, G., Liao, H., Zhang, C., Fu, S., Chen, T., Cai, J., Zhong, X., Chen, C., Huang, M., Cheng, Y., & Pan, M. (2023). Plasma-only circulating tumor DNA analysis detects minimal residual disease and predicts early relapse in hepatocellular carcinoma patients undergoing curative resection. Frontiers in Oncology, 13, 1119744. https://doi.org/10.3389/fonc.2023.1119744
Gu, Y., Luo, X., Zhang, Y., Tang, J., & Wang, Z. (2026). Circulating tumor DNA for minimal residual disease and recurrence surveillance in hepatocellular carcinoma: Current evidence and a translational roadmap. Frontiers in Oncology, 16, 1920559. https://doi.org/10.3389/fonc.2026.1920559

