ctDNA-guided treatment decisions are entering routine oncology care

What ctDNA is and how it is used in oncology

Circulating tumour DNA (ctDNA) is fragmented DNA shed by tumour cells into the bloodstream. A blood draw can capture and sequence this DNA and, depending on the assay, identify mutations, copy-number changes, fusions and methylation patterns characteristic of the patient's tumour. Compared with tissue biopsy, ctDNA is less invasive, can be repeated frequently, and captures the tumour molecular profile across all anatomical sites rather than just the biopsied lesion.

The four use cases that have moved into routine practice are:

• Treatment selection: identifying actionable mutations to guide targeted therapy choice, particularly in NSCLC, colorectal cancer, breast cancer and prostate cancer
• Monitoring on therapy: tracking ctDNA levels as a real-time response readout, with rising levels prompting earlier intervention
• Minimal residual disease (MRD) detection: identifying patients with detectable ctDNA after curative-intent surgery who are at high risk of recurrence
• Recurrence surveillance: detecting molecular recurrence ahead of imaging findings, with growing evidence that earlier intervention improves outcomes

What is now routine and what is still emerging

Treatment selection via ctDNA is routine in advanced NSCLC at progression on first-line therapy and in advanced colorectal cancer for KRAS, NRAS, BRAF and HER2 status. Tissue is still the reference standard for initial diagnosis in most settings, but ctDNA is the practical option for sequential testing across the patient journey.

MRD detection in early-stage disease is the rapidly emerging use case. The evidence base for ctDNA-MRD-positive patients benefiting from intensified or extended adjuvant therapy is firming up in colorectal cancer and is in earlier stages in breast cancer and other indications.

Recurrence surveillance is the use case where the evidence base is most active. Detecting molecular recurrence months ahead of imaging findings is well-established as a biological observation; whether earlier intervention based on the molecular signal improves overall survival is the open clinical question.

The reimbursement picture

ctDNA testing reimbursement varies materially by country, indication and use case. Treatment-selection use is broadly covered in most major markets. MRD and recurrence-surveillance use is reimbursed less consistently, and that is the single biggest determinant of equitable access to the modality across the patient journey.

For commercial planning purposes, ctDNA-driven treatment selection is now a baseline assumption in oncology asset development. MRD-positive populations are increasingly being included as predefined subgroups in clinical trial designs, and that signals where the next reimbursement conversations will land.