Liquid biopsy is a non-invasive test that uses next-generation sequencing to analyse the tumour-derived fragments (ctDNA) within the cell-free DNA (cfDNA) circulating in the blood. In advanced cancer it reveals the mutations that guide treatment, resistance mechanisms and how the tumour changes over time, without the need for a tissue biopsy; negative results are confirmed by tissue analysis.
How does it work?
All cells release small fragments of DNA into the blood when they die; this is known as cell-free DNA (cfDNA). In cancer patients, a proportion of these fragments comes from tumour cells and is called circulating tumour DNA (ctDNA). Plasma is separated from a blood sample collected in a special tube, the cfDNA is isolated and hundreds of genes are sequenced at high depth; tumour-specific mutations, copy number changes and gene fusions are detected.
ctDNA usually makes up only a very small percentage of total cfDNA. The sensitivity of the test therefore depends on tumour burden, cancer type and the site of metastasis: ctDNA is detected more readily in advanced, widespread disease, whereas it may be undetectable in early-stage tumours or those located in the brain.
When is it preferred?
According to the 2022 recommendations of the European Society for Medical Oncology (ESMO), ctDNA testing is a valid route to treatment-guiding genotyping in advanced cancer when a tissue sample cannot be obtained, is insufficient, or when results are needed quickly1. Its main uses are:
- Selecting targeted therapy in lung, breast, colorectal, prostate and other solid tumours (EGFR, ALK, KRAS, BRAF, PIK3CA, ESR1, BRCA and others)
- Capturing resistance mutations that emerge during treatment (for example ESR1 after an aromatase inhibitor)
- Reflecting the differing make-up of several metastatic sites in a single sample
- A molecular update before a change of treatment in patients for whom repeat biopsy is risky or not possible
What are its limitations?
In the same document, ESMO clearly states two limitations: a negative or uninformative ctDNA result does not mean that the tumour has no mutation; it should be confirmed by tissue testing where possible. In addition, liquid biopsy is not recommended for cancer screening or early detection outside clinical trials1. Because clonal haematopoiesis variants that accumulate in blood cells with age can also cause false positives, these are assessed separately in the report.
Comparison with tissue biopsy
| Tissue (CanAct® X Solid) | Liquid (CanAct® X Liquid) | |
|---|---|---|
| Sample | Paraffin-embedded tumour tissue (FFPE) | Blood collected in a special tube (cfDNA) |
| Procedure | Biopsy or surgical specimen | Standard blood draw, a few minutes |
| Coverage | 523 genes DNA + 55 genes RNA fusion, TMB and MSI | 523 genes DNA + 23 genes RNA fusion |
| Strength | Gold standard; required for tumours in which ctDNA is undetectable | Fast and repeatable; captures resistance and tumour heterogeneity |
| Limitation | Represents a single site; cannot always be obtained | May give a false negative when tumour burden is low |
| Turnaround | 3–4 weeks | 3–4 weeks |
Liquid biopsy at Lue GEN: CanAct® X Liquid
CanAct® X Liquid is a comprehensive genomic profiling test that examines 523 genes and RNA fusions in 23 genes from cell-free tumour DNA circulating in the blood. For each alteration detected, the report lists the AMP/ASCO/CAP level of evidence, treatment options referenced to the FDA and NCCN, and matching clinical trials. The sample is collected into a cell-free DNA tube at Akasya Partner Clinics; the test is planned with a physician's assessment and the report is sent to your oncologist.
Questions about liquid biopsy
Does liquid biopsy replace tissue biopsy?
Not always. Tissue biopsy is the gold standard; liquid biopsy is preferred when tissue cannot be obtained, when repeat biopsy is risky, or when the tumour's evolution needs to be monitored during treatment. A negative ctDNA result is confirmed with tissue where possible.
Can I have a liquid biopsy for cancer screening?
No. Current guidelines do not recommend liquid biopsy for screening or early detection outside clinical trials. If you want to learn about your hereditary risk, the OncoSeq panels, run on a blood sample, are designed for that purpose.
How is the blood taken, and is any special preparation needed?
It is a standard blood draw using a special cell-free DNA tube. Fasting is not required. For timing after a chemotherapy cycle, your oncologist's advice is sought.
How long does the result take?
The CanAct® X Liquid report is usually ready 3–4 weeks after the sample reaches the laboratory and is sent to your physician.