The Method Used When Tissue Is Inaccessible: When Is Liquid Biopsy Preferred?
Accessing genetic information to diagnose cancer is now almost standard practice.
But how do we access that information?
Sometimes everything goes according to the textbook: the tumor is imaged, a biopsy is taken, the tissue is analyzed, a mutation is found, and treatment is planned. But in the field, things don’t always go that smoothly. The tumor is deep. The patient cannot tolerate the risk of the procedure. A biopsy is taken, but is insufficient for genetic analysis. Or the tissue is available but there is no time.
Therefore, in situations where tissue cannot be accessed or a repeat biopsy cannot be performed, liquid biopsy becomes an important option for accessing genetic information.
At first glance, liquid biopsy may seem like a simple procedure: obtaining information about a tumor with just a tube of blood. However, behind the scenes, it is an extremely complex process involving the intersection of cell biology and advanced molecular technologies, ranging from cellular death mechanisms to genetic variant analysis.
As cells in our body die during their natural cycle, they break down and small fragments of their DNA enter the bloodstream. These fragments are referred to as cell-free DNA (cfDNA). cfDNA is also present in healthy individuals; for example, cfDNA originating from hematopoietic cells or endothelial cells circulates in the bloodstream. However, cancer cells undergo more necrosis and apoptosis. During this process, DNA fragments carrying tumor-specific genetic alterations are also released into the bloodstream; these are called circulating tumor DNA (ctDNA).
The ratio of ctDNA within cfDNA is variable. In early-stage tumors, this ratio is below 0.1%, while in advanced metastatic cases, it can exceed 10%. Due to these low ratios, the sensitivity of the analysis method used is of great importance. Methods with high sensitivity, such as ultra-deep sequencing or allele-specific PCR, should be preferred. Additionally, the half-life of ctDNA is approximately 2 hours, which provides a major advantage for dynamic tumor monitoring.
Thanks to this technology, now:
- Genetic analysis can be performed in patients where tissue cannot be accessed. For example, in inoperable lung nodules or brain tumors carrying neurological risk, liquid biopsy is becoming almost the only method for obtaining genetic information.
- Response to treatment or development of resistance can be monitored. Especially in patients with targetable mutations such as EGFR and ALK, ctDNA analysis can be repeated to monitor for resistance mutations, offering a non-invasive monitoring option.
- Tumor recurrence or minimal residual disease (MRD) detection is possible. Some studies show that residuals invisible on radiological imaging can be detected much earlier using ctDNA.
However, this method is not always a “miraculous” alternative that replaces tissue biopsy. The detection of ctDNA depends on many factors, such as tumor type, burden, vascularity, and biological behavior. For example, some brain tumors, such as glioblastoma, provide limited information from liquid biopsy due to the amount of cfDNA that cannot cross the blood-brain barrier. Furthermore, advantages offered by tissue biopsy, such as histopathological confirmation and tumor microenvironment analysis, cannot be obtained with liquid biopsy.
For this reason, liquid biopsy is now positioned as a tool that complements tissue-based analyses and, in certain clinical situations, can temporarily replace them. When tissue cannot be obtained, time is limited, or the patient is unsuitable due to their general condition, liquid biopsy can open a life-saving window.
We are also observing a marked increase in interest in liquid biopsy in the field. It has become one of the most frequently asked questions by clinical teams, especially in cases of metastatic disease or when insufficient tissue is obtained during the diagnostic process: “Can we study this patient with liquid biopsy?”
Today, we can often answer this question with a “yes”. Moreover, we support these analyses not only with NGS but also with faster and more cost-effective platforms such as digital PCR and real-time PCR. Click here to explore our liquid biopsy products.