Patient Selection and Implementation Strategies for MRD Testing

As the clinical evidence around ctDNA testing continues to evolve, health care providers face the challenge of integrating these advances into everyday practice while ensuring clear communication with patients. In clinical settings, many providers are beginning to use ctDNA testing for surveillance after initial treatment, particularly in the adjuvant setting. A common approach when encountering a positive ctDNA result is to repeat the test to confirm whether the positivity is persistent or increasing, which informs decisions about potential changes in therapy. This cautious strategy helps balance the benefits and risks of interventions in a landscape where data are still emerging.

Frequency of ctDNA testing varies by cancer subtype and clinical follow-up schedules. Providers tend to test more often—typically every 3 to 6 months—in patients with more aggressive subtypes, such as triple-negative and HER2-positive breast cancer, especially during the first 5 years post treatment. For patients with hormone receptor–positive, HER2-negative disease, testing often begins later and may be conducted less frequently, aligned with annual follow-up visits after 5 years. Real-world data also show that some providers are already making therapeutic changes based on ctDNA results, including switching treatments or initiating targeted therapies such as PARP inhibitors in patients with BRCA mutations, even if these patients fall outside traditional eligibility criteria.

Barriers to widespread ctDNA testing remain, with education emerging as a significant hurdle. Providers require a clearer understanding of the differences between tumor-informed and tumor-agnostic assays, as well as between tissue-based next-generation sequencing and liquid biopsy monitoring. Despite initial concerns, insurance coverage for ctDNA testing and related imaging has been relatively accessible, with few denials reported. As knowledge and comfort with ctDNA testing grow, its role in personalized cancer care is expected to expand, guiding more precise surveillance and treatment decisions.