ASCO Publishes First-Ever Guideline on ctDNA Testing in Solid Tumors and Lymphoma

The American Society of Clinical Oncology查看公司主页 (ASCO) has published its first formal guideline on the use of circulating tumor DNA (搜索)搜索该靶点 (ctDNA) testing in patients with solid tumors (搜索)搜索该疾病 or lymphoma (搜索)搜索该疾病, marking a pivotal moment for precision oncology. Approved by an ASCO expert panel on November 18, 2025, and published online in JCO Oncology Practice on June 18, 2026, the guideline establishes evidence-based recommendations addressing when blood-based ctDNA testing should—and should not—be employed across four clinical scenarios: supporting cancer diagnosis, guiding initial therapy selection and therapeutic monitoring, aiding surveillance and recurrence monitoring, and informing prognosis.

"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."

An Evidence Base Spanning Seven Years

The recommendations draw on a substantial body of literature. Building on a 2018 joint systematic review conducted by ASCO and the College of American Pathologists, the expert panel performed a new systematic review of articles published on or after January 1, 2017, alongside a systematic review of clinical trials in which ctDNA testing was used to select care, conducted on October 24, 2025. In total, 54 relevant meta-analyses, 12 reports from 11 randomized clinical trials, and 489 other articles informed the guideline.

"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.

When to Use ctDNA Testing—and When to Refrain

The guideline delineates clear parameters for clinical practice. Outside of a clinical trial, ctDNA testing should be offered only if results 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 is appropriate when tissue-based testing is challenging or poses an unacceptable risk to the patient, when tissue testing results may not be available within a clinically actionable timeframe, or when a drug's approved indication allows for or requires ctDNA testing.

The panel also advises that ctDNA testing may be offered alongside standard-of-care testing when an evidence-based decision can be made from the results or when testing may help resolve a conflict or ambiguity. Critically, ctDNA testing is not recommended as a replacement for any other form of testing. Furthermore, fractional, percentage, or concentration-based measures of ctDNA or total cell-free DNA (cfDNA) should not be used as a surrogate measure of disease burden outside of a clinical trial or clinical research.

Dr. Gray expects 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.

Specificity, Sensitivity, and the Caution Around Negative Results

Dr. Lockwood emphasized that ctDNA testing offers distinct advantages over tissue biopsy, including its minimally invasive nature and the high 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 explained. "But if you have a negative result, that doesn't guarantee that no mutation is present."

The guideline does not address the use of ctDNA testing as a screening tool, given the current lack of sufficient evidence. Dr. Lockwood described this as "absolutely an area where all of us want to see more investigation and more of an evidence base." Similarly, the panel declined to endorse concentration-based ctDNA tests as surrogates for disease burden outside clinical trials. "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 Snapshot in a Rapidly Evolving Field

Both co-chairs underscored that ctDNA testing is a complementary tool, not a replacement for standard-of-care approaches such as imaging. Because the current guideline is broadly applicable to all solid tumors (搜索)搜索该疾病, cancer type–specific guidelines will be necessary as the evidence base continues to mature.

"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.