Clinical bottom line
Liquid biopsy technologies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), offer promising noninvasive approaches for early detection and monitoring of recurrence in high-risk cancer patients. Evidence supports their utility in several solid tumors, notably non-small cell lung cancer (NSCLC), colorectal, breast, and endometrial cancers. These assays can detect minimal residual disease (MRD) and molecular relapse earlier than conventional imaging, potentially enabling timely intervention. However, sensitivity varies by cancer type and stage, and clinical integration requires further validation and standardization.
What the evidence shows
In NSCLC, Feng et al. (2026) demonstrated that a tumor-informed plasma ctDNA assay effectively identifies patients with high-risk stage I disease, predicting recurrence risk post-surgery. This supports ctDNA’s role in MRD detection and risk stratification.
Abdayem et al. (2021) reviewed molecular pathology advances and liquid biopsy applications in NSCLC, highlighting ctDNA’s growing role in guiding targeted therapies and monitoring resistance.
Raval et al. (2025) detailed how liquid biopsy transforms colorectal cancer management by enabling early detection, precision treatment adjustments, and recurrence monitoring through serial ctDNA analysis.
Martos et al. (2020) summarized applications of circulating tumor cells in early breast cancer, noting their prognostic significance and potential to guide adjuvant therapy decisions.
Muinelo-Romay et al. (2018) discussed liquid biopsy opportunities in endometrial cancer, emphasizing personalized oncology approaches facilitated by ctDNA and other circulating biomarkers.
Heidrich et al. (2023) reviewed liquid biopsy utility in monitoring tumor dormancy and early recurrence detection across solid tumors, underscoring its potential to inform surveillance strategies.
Devaraji et al. (2024) focused on oral cancer, demonstrating that liquid biopsy can detect molecular changes preceding clinical recurrence, offering a window for early intervention.
Caveats and uncertainty
Despite promising data, liquid biopsy sensitivity and specificity vary widely depending on tumor burden, biology, and assay methodology. False negatives remain a concern, particularly in low-volume disease or certain tumor types.
Standardized protocols for sample collection, processing, and interpretation are lacking, limiting cross-study comparability and clinical adoption.
Clinical trials demonstrating improved patient outcomes based on liquid biopsy-guided interventions are limited, and cost-effectiveness analyses are needed.
Integration with existing imaging and biomarker surveillance requires careful consideration to avoid overtesting or unnecessary interventions.
How this may change practice
Liquid biopsy has the potential to revolutionize post-treatment surveillance by enabling earlier detection of molecular relapse, allowing for prompt therapeutic adjustments before radiologic progression.
Incorporating ctDNA or CTC assays into routine follow-up could personalize surveillance intensity, reducing unnecessary imaging and associated costs.
Oncologists should remain informed about emerging evidence and evolving guidelines to identify patients who may benefit from liquid biopsy monitoring, particularly in high-risk early-stage cancers.
Future clinical trials should focus on validating liquid biopsy-driven treatment algorithms and defining optimal timing and frequency of testing.