Liquid Biopsy and ctDNA Testing: What the Latest ASCO Guideline Means for Cancer Care

Circulating Tumor DNA Testing in Solid Tumors and Lymphoma ASCO Guideline.pdf

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Circulating tumor DNA, or ctDNA, has become one of the most important developments in precision oncology. By analysing small fragments of tumor-derived DNA released into the bloodstream, clinicians may gain valuable genomic information from a simple blood sample. This approach, often called liquid biopsy, can support treatment selection, disease monitoring, and, in selected settings, help guide clinical decision-making.

A new ASCO guideline on ctDNA testing in solid tumors and lymphoma provides timely guidance on where ctDNA testing is useful, where evidence is still developing, and where caution is needed. The guideline was developed from a systematic review of evidence, including 54 meta-analyses and multiple clinical studies.

What is ctDNA?

ctDNA is a portion of cell-free DNA found in blood. While cell-free DNA can come from many normal body cells, ctDNA specifically comes from tumor cells. Because cancer cells often carry genetic alterations, ctDNA testing can help detect tumor-related mutations without needing another invasive tissue biopsy. However, not all cell-free DNA is tumor-derived, so sensitive laboratory methods and careful clinical interpretation are essential.

When ctDNA testing may be useful

The ASCO guideline supports the use of ctDNA testing for tumor genetic alterations in selected situations. These include cases where tissue biopsy is difficult, unsafe, not feasible, or when tissue test results may not be available quickly enough to guide treatment. ctDNA testing may also be appropriate when a drug’s approved indication allows or requires ctDNA testing.

This is highly relevant in precision oncology, especially for patients with advanced cancers where timely genomic profiling may identify actionable targets for targeted therapy or immunotherapy.

A negative liquid biopsy does not always mean “no mutation”

One of the most important messages from the guideline is that a positive ctDNA result can be clinically useful, but a negative or inconclusive result must be interpreted carefully. If ctDNA testing is negative, inconclusive, or does not match the clinical picture, tissue-based testing should be pursued whenever possible.

This is because some tumors shed very little DNA into the blood, and the amount of ctDNA can vary depending on tumor type, disease burden, stage, treatment status, and sample quality.

ctDNA should support, not replace, standard cancer care

ASCO emphasizes that ctDNA testing should only be offered outside a clinical trial when the result can meaningfully guide clinical decision-making. It should not be used simply because the technology is available. The guideline also states that ctDNA testing is not recommended as a complete replacement for other standard tests, except in specific circumstances where evidence supports its use.

This means liquid biopsy should be viewed as a powerful complement to tissue biopsy, imaging, pathology, and clinical assessment—not a standalone answer for every cancer question.

What about monitoring, recurrence, and MRD?

ctDNA testing is gaining strong interest in molecular residual disease, recurrence monitoring, and treatment response assessment. Studies show that the presence of ctDNA after treatment is often associated with a higher risk of relapse. However, ASCO notes that evidence is still evolving, and ctDNA testing should be used when there is a clear, evidence-based action that can be taken based on the result.

Several clinical trials are beginning to show where ctDNA-guided decisions may benefit patients. Examples include selected settings in colorectal cancer, breast cancer, lung cancer, and bladder cancer. However, the guideline remains cautious because evidence varies by cancer type, stage, treatment setting, and testing approach.

ctDNA level alone should not be used as a disease burden marker

Another important recommendation is that fractional, percentage, or concentration-based measures of ctDNA or total cell-free DNA should not be used alone as a surrogate for disease burden to make treatment decisions outside clinical trials or research settings.

In practical terms, clinicians should avoid making major treatment decisions based only on “more ctDNA” or “less ctDNA” unless the test and clinical setting have validated evidence behind them.

Communicating results clearly with patients

The guideline also highlights the importance of patient-clinician communication. Patients should understand why ctDNA testing is being ordered, what the result may or may not show, what could change in their care, and what uncertainties remain. If results are uncertain or inconclusive, this should be clearly explained.

Key takeaway

ctDNA testing is transforming precision oncology, but its greatest value comes when it is used thoughtfully. The latest ASCO guideline reinforces a balanced message: liquid biopsy can provide fast, minimally invasive genomic information, especially when tissue testing is difficult or delayed. However, ctDNA testing should be integrated with clinical judgment, tissue pathology, imaging, and evidence-based treatment pathways.

At AGTC Genomics, we believe the future of cancer care lies not only in advanced genomic technology, but also in responsible interpretation, multidisciplinary collaboration, and patient-centered decision-making. Liquid biopsy is not just a test—it is part of a broader precision oncology ecosystem designed to help clinicians make more informed decisions for patients.