What it is exactly
As tumour cells die or turn over, they shed small fragments of their DNA into the blood: this is circulating tumour DNA or ctDNA. A "liquid biopsy" means taking a tube of blood, separating that DNA from normal DNA and analysing it with highly sensitive techniques (digital PCR or sequencing). It can show the tumour's mutations and, with finer methods, whether tumour remains in the body even when scans show nothing.
Not to be confused with CEA, which is a protein and a far less specific marker, nor with genetic blood tests for hereditary syndromes (Lynch), which analyse your normal DNA, not the tumour's.
Use 1: learning the mutations without another biopsy
When there is not enough tissue, a biopsy is difficult or the tumour may have changed with treatment, a liquid biopsy allows RAS, BRAF and other alterations to be analysed in blood. Its most established application in colon cancer is anti-EGFR "rechallenge": in RAS wild-type patients who responded to cetuximab or panitumumab and then progressed, the tumour usually acquires RAS resistance mutations; over time those clones fade. A liquid biopsy showing RAS wild-type in blood identifies those who may benefit from the anti-EGFR again in later lines. Read more in KRAS mutation.
Agreement between blood and tissue is high (around 90 % in metastatic disease), but if the liquid biopsy detects nothing, it does not mean there is no mutation: some tumours shed little DNA (for example when disease is only in the peritoneum or lungs).
Use 2: minimal residual disease after surgery
Weeks after surgery, if ctDNA is detected in blood it means tumour cells remain somewhere, even if the CT is normal: the risk of relapse is very high. If it is not detected, the risk is low. This opens the possibility of:
- Avoiding chemotherapy in those who do not need it: in stage II, the DYNAMIC study halved the use of chemotherapy without worsening relapse-free survival. See stage II.
- Intensifying treatment or monitoring more closely those with positive ctDNA. Whether this improves survival is still being demonstrated in trials (in stage III, for example, the results are more complex).
- Detecting relapse earlier than CT, by months. Whether that earlier detection leads to more cures is what remains to be proven.
Limits you should know
- False negatives: the test may fail to detect DNA even when disease is present, especially if there is little of it or it is in sites that shed little ctDNA. A negative result is reassuring but not a guarantee.
- Anxiety and difficult decisions: a positive result with a normal CT tells you something is there, but not where or what to do; outside a trial it can create more distress than benefit.
- It does not replace CT or CEA in standard follow-up, nor tissue biopsy for the initial diagnosis and MSI testing.
- There are many different tests, with very different sensitivities and prices; not all are validated for the same purpose.
Availability in Spain
Liquid biopsy for RAS/BRAF in metastatic disease is available in many public reference hospitals and, when indicated (for example for rechallenge or when there is no tissue), the hospital itself performs it. Detection of minimal residual disease after surgery is done mainly within clinical trials or in programmes at specific centres; it is not yet part of publicly funded standard follow-up. Ask whether there is an open trial at your hospital or search our guided trial finder.
In the private sector some laboratories offer it for a fee. Before paying for it, ask your oncologist whether the result would change any decision: if it would change nothing, the cost and the anxiety are not worth it.
What to ask at your appointment
- In my situation, would a liquid biopsy change my treatment? What would you use it for?
- If I am RAS wild-type and have progressed after an anti-EGFR: would you do a liquid biopsy to consider a rechallenge?
- Is there a ctDNA (minimal residual disease) trial I could join?
- If the result is negative, how reliable is it in my case?
- If I have it done privately, would you take it into account?
