A panel of ASCO experts voted to approve ASCO’s first guideline on ctDNA testing in patients with solid tumors or lymphoma on November 18, 2025.1 The guideline addresses four overarching clinical questions: when ctDNA testing should (or should not) be used to (1) support cancer diagnosis; (2) assist with choice of initial therapy and therapeutic monitoring; (3) assist with surveillance, monitoring for recurrence, relapse, and/or progression; and (4) aid with prognosis.
Christina M. Lockwood, PhD, DABCC, DABMGG
“We’re trying to provide clinically useful, meaningful guidance for oncologists across all practice settings on when to use ctDNA testing,” said Guideline Co-Chair Christina M. Lockwood, PhD, DABCC, DABMGG, of the University of Washington School of Medicine. “It’s a powerful tool but really does need to be used appropriately—so the context of when you use testing is part of what we really wanted to elucidate.”
Recommendations Informed by Meta-Analyses and Clinical Trials
In 2018, ASCO and the College of American Pathologists conducted a joint systematic review to assess the clinical validity and utility of ctDNA testing, as well as its value in interpretation and reporting.2 Since then, the number of published studies on ctDNA has increased substantially, pointing to the value of ctDNA testing in cancer detection, monitoring, and treatment response, and prompting a need for the development of ASCO’s first formal guideline on blood-based ctDNA testing.
The recommendations were developed based on data from two sources: the systematic review from 2018, and a new systematic review of articles published on or after January 1, 2017, that were not included in the review by Merker et al.2 In addition, a systematic review of clinical trials in which ctDNA testing was used to select care was conducted on October 24, 2025. These reviews returned 54 relevant meta-analyses, 12 reports of 11 randomized clinical trials, and 489 other articles, which were used to inform guideline recommendations.
Stacy W. Gray, MD, AM, FASCO
“There has been a tremendous amount of literature published between 2018 and 2025 in this space, and we really needed to further look at both the clinical validity of ctDNA testing and, particularly, the clinical utility of ctDNA testing,” noted Guideline Co-Chair Stacy W. Gray, MD, AM, FASCO, of City of Hope.
The Do’s and Don’ts of ctDNA Testing
Per the literature review, the expert panel has provided the following recommedations:
- Outside of a clinical trial, ctDNA testing should be offered only if the results of testing could be useful in clinical decision-making; however, it may be used to determine a patient’s eligibility for a clinical trial.
- ctDNA testing for tumor genetic alterations may be used when (1) tissue-based testing is challenging or represents an unacceptable risk to the patient, (2) the results of tissue testing may not be available within a clinically actionable timeframe, or (3) a drug’s approved indication allows for or requires ctDNA testing.
- ctDNA testing may be offered together with standard-of-care testing when an evidence-based decision can be made based on the results or in those cases when testing may aid in resolving a conflict or ambiguity.
- ctDNA testing is not recommended as a replacement for any other form of testing.
- Fractional, percentage, or concentration-based measures of ctDNA or total cell-free DNA (cfDNA) may not be used as a surrogate measure of disease burden outside of a clinical trial or clinical research.1
Dr. Gray expects that the greatest utility of these recommendations will be in guiding therapeutic decision-making for targeted therapies.
“I think that we have a lot of data in this space showing that if ctDNA testing finds tumor genetic alterations, the findings are reliable and that we can use them to help with treatment selection,” she said.
In addition, Dr. Lockwood noted that the advantages of ctDNA testing over tissue testing include its minimally invasive nature and high degree of specificity of positive results.
“When you get a positive result, fantastic—you can use that information in diagnosis potentially if you can’t obtain tumor tissue and absolutely for therapy selection since that’s where we have the best evidence,” she said. “But if you have a negative result, that doesn’t guarantee that no mutation is present.”
Although the recommendations do not address the use of ctDNA testing as a screening tool, Dr. Lockwood is excited about the emerging clinical trial data about its potential use in the preventive setting.
“That’s an area that we’re not addressing in this guideline because there’s not [a] sufficient evidence base for us to make a recommendation,” she said. “However, this is absolutely an area where all of us want to see more investigation and more of an evidence base.”
Finally, because of a lack of suitable evidence, the recommendations do not endorse the use of concentration-based ctDNA (eg, percent of cfDNA or fractional cfDNA) tests as a surrogate measure of disease burden outside of a clinical trial.
“A clinical trial is the perfect time to be investigating these types of findings and helping us to understand how to act on them,” Dr. Lockwood said. “But [at the moment] we don’t have a strong evidence base, and so we’re not making specific guidance outside of a clinical trial in that context.”
Dr. Gray added that prior studies across many cancer types have pointed to poorer outcomes for patients who remain ctDNA positive after surgery.
“What we need to do now is figure out how to intervene so that we can improve patient outcomes,” she said.
A Complementary Tool, Not a Replacement for Standard Testing
Although the clinical utility of ctDNA testing is expected to expand over time, both guideline co-chairs noted that, at present, it should be used as a complementary tool and not as a replacement for standard-of-care testing such as imaging. Moreover, because the current guideline is broadly applicable to all solid tumors, cancer type–specific guidelines will be necessary in the future.
“This is a really rapidly evolving field, so this is a snapshot that we’re providing today, and we absolutely expect that more will be coming,” Dr. Lockwood concluded.
REFERENCES
1. Lockwood CM, Messersmith HJ, Kim AS, et al: Circulating tumor DNA testing in solid tumors and lymphoma: ASCO Guideline. JCO Oncol Pract. Published online June 18, 2026.
2. Merker JD, Oxnard GR, Compton C, et al: Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol 36:1631-1641, 2018.
