Assessing response to immunotherapy remains challenging, particularly early in treatment when radiographic changes can be difficult to interpret. New research suggests that circulating tumour DNA (ctDNA) may provide a dynamic and non-invasive way to track treatment effect and identify resistance earlier than imaging alone.
A recent study published in npj Precision Oncology evaluated the use of ultrasensitive, tumour-informed ctDNA assays to monitor patients with advanced solid tumours treated with immune checkpoint inhibitors, examining whether early molecular changes correlated with clinical outcomes.
Investigators performed serial ctDNA testing in patients receiving immunotherapy and correlated ctDNA dynamics with progression-free survival (PFS), overall survival (OS), and radiographic response. Rather than relying on generic mutation panels, the assay was customised to each patient’s tumour profile, allowing detection of very low levels of residual disease.
CLINICAL SUMMARY
What was examined
Serial tumour-informed ctDNA monitoring in patients receiving immune checkpoint inhibitors, and its association with survival and radiographic outcomes.
Key findings
-
Early ctDNA clearance or marked reductions were associated with significantly improved progression-free and overall survival.
-
Persistently detectable or rising ctDNA predicted poor outcomes.
-
ctDNA changes often preceded radiographic progression.
Clinical implications
-
ctDNA may provide a non-invasive, real-time biomarker of immunotherapy benefit.
-
Molecular response assessment could help distinguish true progression from atypical imaging patterns.
-
Prospective validation is required before routine clinical adoption.
The study aimed to determine whether early ctDNA clearance or persistence could act as a real-time biomarker of immunotherapy benefit or failure.
Patients who achieved early ctDNA clearance or major reductions after starting immunotherapy had significantly better outcomes than those with persistently detectable ctDNA. Molecular responders experienced substantially longer PFS and OS, while rising or stable ctDNA levels were associated with early disease progression.
Notably, ctDNA changes frequently preceded radiographic progression, indicating that molecular relapse could be detected weeks to months earlier than conventional imaging. This suggests that ctDNA may provide an earlier signal of treatment failure, potentially enabling faster clinical decision-making.
Importantly, the study showed that ctDNA response stratified outcomes even within radiographically stable disease, highlighting its potential role in refining response assessment beyond RECIST alone.
HER2 Uncovered: From Low to Ultralow – Get the Low Down with Ben Dessauvagie & Gelareh Farshid
Immune checkpoint inhibitors can produce atypical response patterns, including pseudoprogression, complicating treatment decisions. A reliable blood-based biomarker could help distinguish true progression from delayed response and reduce unnecessary treatment discontinuation.
If validated prospectively, ctDNA monitoring could support earlier treatment modification, reduce exposure to ineffective therapies, and improve patient counselling about the likelihood of benefit. It may also help guide treatment escalation or de-escalation strategies as combination immunotherapy regimens become more common.
While the findings are not yet practice-changing, they strengthen the case for ctDNA as a response biomarker, rather than only a tool for minimal residual disease detection, and point toward a future role in routine immunotherapy monitoring.
Paper: Nishizaki, D., Law, A., Li, B. et al. Ultrasensitive ctDNA monitoring reveals early predictors of immunotherapy response in advanced cancer. npj Precis. Onc. (2026). Access online here.
