Clinical bottom line
Circulating tumor DNA (ctDNA) analysis is a promising minimally invasive approach for monitoring minimal residual disease (MRD) and predicting recurrence risk after curative-intent surgery across multiple solid tumors, including colorectal, lung, and breast cancers. Recent evidence supports ctDNA’s role in guiding adjuvant therapy decisions and enabling earlier detection of relapse, although standardization and prospective validation remain ongoing challenges.
What the evidence shows
Chidharla et al. (2023) conducted a systematic review and meta-analysis evaluating ctDNA as an MRD biomarker in colorectal cancer patients undergoing curative surgery with or without adjuvant chemotherapy. Their findings indicate that postoperative ctDNA positivity strongly predicts recurrence risk, with hazard ratios consistently exceeding 7, underscoring its prognostic value.
Chen et al. (2023) demonstrated the utility of individualized tumor-informed ctDNA assays for postoperative monitoring in non-small cell lung cancer (NSCLC). Their study showed that ctDNA detection preceded radiographic relapse by several months, enabling earlier intervention opportunities.
Elliott et al. (2025) applied ultrasensitive detection of structural variants in ctDNA to monitor MRD in early-stage breast cancer. This approach improved sensitivity and specificity for recurrence prediction compared to conventional mutation-based assays.
Powles et al. (2025) reported on a ctDNA-guided adjuvant immunotherapy trial in muscle-invasive bladder cancer, where ctDNA-positive patients receiving atezolizumab had improved disease-free survival compared to observation, illustrating ctDNA’s potential to personalize adjuvant treatment.
Andersen et al. (2025) advanced MRD monitoring by integrating whole-genome sequencing of ctDNA in breast cancer, enhancing detection of genomic alterations and facilitating dynamic disease tracking.
Additional studies have confirmed ctDNA’s role as a surrogate for MRD in colorectal cancer (2018) and its growing clinical adoption for monitoring treatment response and recurrence risk (2022, 2023).
Caveats and uncertainty
Heterogeneity in ctDNA assay platforms, sensitivity thresholds, and timing of sampling complicates cross-study comparisons and clinical implementation.
False negatives may occur due to low tumor shedding or assay limitations, while false positives can arise from clonal hematopoiesis or technical artifacts.
Optimal integration of ctDNA results with imaging and clinical parameters requires further study.
Prospective randomized trials demonstrating improved patient outcomes from ctDNA-guided interventions are limited but emerging.
Cost, access, and reimbursement issues currently restrict widespread use.
How this may change practice
Incorporating ctDNA MRD assessment postoperatively can refine recurrence risk stratification, enabling more personalized adjuvant therapy decisions and potentially sparing low-risk patients from overtreatment.
Serial ctDNA monitoring may allow earlier detection of relapse, facilitating timely therapeutic interventions before radiographic progression.
Tumor-informed ctDNA assays tailored to individual mutational profiles improve sensitivity and specificity, supporting precision surveillance strategies.
Multidisciplinary teams should integrate ctDNA data with clinical and radiologic findings to optimize patient management.
Ongoing trials and real-world data will clarify ctDNA’s role in standard care pathways and inform guideline development.