Circulating Tumor DNA Testing in Solid Tumors and Lymphoma: ASCO Guideline

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases, or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide guidance on the use of circulating tumor DNA (ctDNA) testing in patients with solid tumors or lymphoma. METHODS A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2017 to February 2025. Guideline recommendations were based on consideration of the identified evidence. RESULTS Fifty-four meta-analyses and 22 study reports were identified, including reports of seven randomized trials. RECOMMENDATIONS ctDNA testing for tumor genetic alterations may be used in situations where: tumor tissue testing is challenging, not feasible, or tumor biopsy represents unacceptable risks to the patient; tumor tissue testing results may not be available within a clinically actionable time frame to determine appropriate management options; or a drug's regulatory approved indication allows for or requires ctDNA testing. If ctDNA testing results are negative, inconclusive, or inconsistent with the clinical scenario, tissue-based confirmation should be sought. Other than testing for genetic alterations, ctDNA testing may be offered if a specific, evidence-based action can be taken with the results or there is conflict or ambiguity with standard-of-care assessment that may be resolved by ctDNA testing. Fractional, percentage, or concentration-based measures of ctDNA or total cell-free DNA concentration are not recommended as a surrogate measure of disease. The panel recognizes this is a rapidly evolving field and guidelines are anticipated to change, bringing in tumor-type specific recommendations and incorporating more data on molecular residual disease settings. Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines .