Liquid Biopsy

This guide explains what liquid biopsy is, when it’s useful, where it has limitations, how results are interpreted, and what questions to ask your oncologist.

Important: Liquid biopsy does not replace clinical evaluation. In many situations, tissue biopsy remains the gold standard, and a negative liquid biopsy may still require a tissue biopsy. 

1) What is a liquid biopsy?

A liquid biopsy is a test that analyzes cancer-related material circulating in blood, usually from a simple blood draw. The most common signal tested is ctDNA—tiny fragments of tumor DNA released into the bloodstream. 

What can be detected?

Depending on the test platform, liquid biopsy may report:

• Gene mutations (e.g., EGFR, KRAS, BRAF, etc.)

• Gene fusions/rearrangements (some panels)

• Copy number changes (some panels)

• Sometimes broader markers like MSI or blood tumor mutational burden (bTMB) on select assays 

2) What does liquid biopsy help with?

Liquid biopsy is most established for molecular profiling in advanced cancers, particularly when tumor tissue is unavailable, unsafe to obtain, or insufficient for complete testing. 

A) Finding “targetable” mutations (advanced/metastatic cancer)

Doctors often need a mutation report to decide targeted therapy or immunotherapy strategy. In cancers like advanced non-small cell lung cancer (NSCLC), plasma ctDNA testing is commonly used when tissue is limited—but a negative result may need tissue confirmation. 

B) Monitoring treatment response and resistance

In some cases, repeating ctDNA can help:

• Track tumor burden trends

• Identify new resistance mutations that may explain why a treatment stopped working
  This area is growing rapidly, with active efforts toward standardization. 

C) Minimal residual disease (MRD) and early relapse signals (selected settings)

After treatment, ctDNA may detect microscopic disease earlier than imaging in some cancers—but the “routine” use varies by cancer type and guideline position, and insurers/payers may differ in coverage decisions. 

D) When tissue biopsy is difficult

Examples include:

• Tumor location is risky to biopsy

• Patient is unfit for an invasive procedure

• Prior tissue was too small or degraded

• Rapid decision needed and tissue is delayed
  Even then, clinicians interpret results carefully and may still recommend tissue when feasible. 

3) What liquid biopsy cannot reliably do?

Liquid biopsy is powerful—but it has important limitations.

A) It may miss cancer (false negative)

If the tumor is small, slow-shedding, or behind “biologic barriers,” ctDNA in blood may be low. This is why a negative liquid biopsy does not always mean “no mutation” or “no cancer.”

B) It does not fully replace tissue biopsy

Tissue still provides:

• Confirmed diagnosis (cancer type)

• Tumor grade/histology

• Microenvironment details

  Some biomarkers better assessed on tissue

  Guidance emphasizes using liquid biopsy thoughtfully—not as a blanket replacement. 

C) Screening “healthy people” is not the routine standard

Blood-based multi-cancer early detection is an evolving field. For most people, standard screening pathways (e.g., breast, cervix, colon) remain the recommended approach; “screening by liquid biopsy” is not yet a universal routine standard of care. (Your oncologist can advise if any trial or special scenario applies.) 

4) What types of “liquid biopsy” exist?

Most patient-facing “liquid biopsy” refers to ctDNA testing, but the umbrella term can include:

• ctDNA (circulating tumor DNA): most common in clinical practice 

• CTCs (circulating tumor cells): intact tumor cells in blood (less commonly used for routine treatment decisions)

• cfRNA / exosomes / methylation signals: more specialized and often research or selected use-cases

For most patients, your report will be a plasma ctDNA NGS panel.

5) Who should consider a liquid biopsy?

Liquid biopsy is most often considered when:

• You have advanced/metastatic solid tumor and need molecular profiling for treatment selection 

• Tissue biopsy is not possible, too risky, or insufficient

• You need faster molecular results while tissue is being arranged (in some workflows)

It may also be considered for:

• Monitoring resistance in certain cancers (case-by-case) 

• MRD/recurrence risk monitoring in selected cancers and settings (oncologist-guided) 

6) How the test is done (patient experience)

Step-by-step

1. A routine blood sample is collected (usually 1–2 tubes, depending on lab)

2. Plasma is separated and analyzed using NGS or targeted assays

3. Report is issued—turnaround time depends on lab (often days to a couple of weeks)

Safety

• Similar to any blood test—minor pain/bruising is the commonest issue.

Do I need fasting?

• Usually not, unless the lab or your doctor gives specific instructions.

7) How to read a liquid biopsy report

A typical report includes:

A) “Detected” mutations

These may be:

• Actionable (linked to a targeted therapy or guideline pathway)

• Potentially actionable (trial options or evolving evidence)

• Non-actionable (not currently linked to a therapy)

B) “Not detected” mutations

This can mean:

• Mutation truly absent OR

• ctDNA was too low to detect (false negative) 

C) Tumor fraction / assay quality metrics

Some reports include an estimate of tumor DNA fraction—useful for interpretation.

D) Incidental findings and “clonal hematopoiesis”

Sometimes, age-related blood cell mutations can appear and may not reflect the tumor (your oncologist/pathologist interprets this in context).

8) FDA-approved companion diagnostics and why they matter

Some liquid biopsy assays are FDA-approved as companion diagnostics for specific drugs/biomarkers—meaning the test is validated to safely guide use of certain therapies. 

This is important because it strengthens confidence that:

• The test detects the biomarker reliably (for that indication)

• The result can be used to choose the corresponding therapy as per labeling

9) Liquid biopsy in practical decision-making

Doctors often use liquid biopsy in one of these patterns:

Pattern 1: Tissue available but slow → liquid biopsy for speed

• Start plasma testing while awaiting tissue NGS

• If plasma finds an actionable mutation, treatment may start earlier

• If plasma is negative, tissue testing remains essential 

Pattern 2: Tissue not possible/inadequate → liquid biopsy as primary molecular test

• Common in advanced disease when biopsy is risky or insufficient

• Again, negative results may require alternative sampling if feasible 

10) Frequently asked questions

Is liquid biopsy painful?

No—just a blood draw.

Does it replace tissue biopsy?

Sometimes it reduces the need, but often tissue is still required for diagnosis or when plasma is negative. 

Can liquid biopsy detect early cancer?

Research is moving fast, but for most people it’s not a routine substitute for standard screening tests. 

Can it help in head & neck cancers?

Liquid biopsy may be used in selected scenarios (advanced disease profiling, monitoring), but the best approach depends on tumor site, stage, and clinical goals—ask your oncologist whether it adds value in your specific case. 

11) What to ask your oncologist before ordering the test?

• What clinical decision will this test help us make today?

• If the result is negative, what is the next step—tissue biopsy, repeat testing, or alternative sample?

• Which biomarkers are most relevant for my cancer type?

• Is this test a companion diagnostic for therapies we are considering? 

• Will the test be repeated for monitoring? If yes, at what time points?

12) Next steps at I D Cancer Centre

If you are considering liquid biopsy for treatment planning or monitoring, we can guide you on:

• Whether liquid biopsy is appropriate for your case

• Which biomarkers/panels matter most for your cancer type

• How to integrate results with tissue biopsy, imaging, and clinical findings