Liquid Biopsy Reshapes Early Cancer Management: From MRD Detection to Cancer Interception
核心洞察
Liquid biopsy enables detection of molecular relapse up to 28 months before clinical diagnosis in early-stage breast cancer (搜索), as demonstrated in a prospective phase III trial.
Multi-cancer early detection (MCED) approaches show high sensitivity and specificity, with potential to identify pre-malignant lesions amenable to curative intervention.
Persistent ctDNA positivity during neoadjuvant treatment can reveal occult molecular progression despite favorable radiologic response, highlighting limitations of imaging alone.
Liquid biopsy is fundamentally reshaping the landscape of early cancer management, moving the field from reactive treatment toward proactive interception of disease before clinical manifestation. A comprehensive Research Topic published in Frontiers in Oncology (搜索), edited by LP, LG, and CR, brings together cutting-edge studies that span biomarker discovery, multi-cancer early detection (MCED), minimal residual disease (MRD) monitoring, and therapeutic decision-making across multiple tumor types.
The collection underscores a paradigm shift: tumor-derived signals detectable in body fluids—particularly circulating tumor DNA (搜索) (ctDNA)—now enable clinicians to identify molecular relapse well before radiographic progression, opening a window for earlier intervention that could alter disease trajectories.
ctDNA Anticipates Recurrence by Over Two Years in Breast Cancer (搜索)
Among the most striking findings, Appierto et al. demonstrated in a prospective phase III fenretinide prevention trial that ctDNA detection could anticipate loco-regional recurrence in early-stage breast cancer (搜索) up to 28 months before clinical diagnosis. This finding supports the potential integration of ctDNA monitoring into follow-up strategies and risk stratification, offering a lead time that could prove clinically decisive.
The clinical relevance of molecular monitoring is further illustrated by Wang et al., who reported a case of locally advanced hypopharyngeal carcinoma (搜索) in which persistent ctDNA positivity during neoadjuvant treatment revealed occult molecular progression—despite a favorable radiologic response. The case highlights the limitations of imaging alone in assessing treatment response and reinforces the argument for integrating molecular monitoring into clinical decision-making.
Multi-Cancer Early Detection and Cancer Interception
The expansion of MCED approaches represents another major theme. Walter et al. evaluated Carcimun (搜索), an innovative screening blood-based test that detects conformational changes in plasma proteins through optical extinction measurements. The test demonstrated high sensitivity and specificity in distinguishing cancer patients from healthy individuals and subjects with inflammatory conditions, emphasizing the importance of reducing false-positive results in real-world clinical settings.
In an exploratory analysis of the DETECT-A study, Choudhry et al. showed that positive MCED testing may also uncover clinically significant pre-malignant lesions amenable to curative intervention. These findings reinforce the emerging concept of cancer interception—identifying molecular abnormalities before the development of overt invasive disease.
Biomarker Discovery Across Tumor Types
The Research Topic highlights diverse biomarker discovery efforts. Jiang et al. identified a serum three-long noncoding RNA (lncRNA) panel with high diagnostic accuracy for muscle-invasive bladder cancer (搜索). Romero Urrego et al., in a systematic review, documented the growing relevance of circulating microRNAs—derived from both extracellular vesicle and non-extracellular vesicle sources—as promising biomarkers for early breast cancer (搜索) detection, with several candidate miRNAs and panels demonstrating high diagnostic accuracy.
Feng et al. reviewed the clinical utility of different liquid biopsy samples for ovarian cancer (搜索) early detection, including plasma, urine, uterine lavage, and cervicovaginal specimens, emphasizing the growing role of multi-omics approaches. Wang et al. demonstrated the feasibility of detecting cell-free DNA from both peripheral blood and Papanicolaou smears in endometrial cancer (搜索), suggesting that minimally invasive gynecologic sampling may complement blood-based and tissue assays.
Guiding Therapeutic Strategies
Liquid biopsy is also showing promise in guiding treatment intensity. Hollander and Nonaka conducted a meta-analysis demonstrating high diagnostic performance of cell-free HPV-DNA in HPV-positive head and neck squamous cell carcinoma (搜索), supporting its possible use as a biomarker to guide treatment de-intensification. Conversely, Kravchuk et al. described dynamic assessment of blood microsatellite instability during immunotherapy in a colorectal cancer (搜索) patient, suggesting that longitudinal liquid biopsy monitoring may provide clinically relevant information on treatment response and hyperprogressive disease.
Cox et al. reviewed the multifaceted role of liquid biopsy in pancreatic ductal adenocarcinoma (搜索), covering applications from early detection and molecular subtyping to treatment monitoring and MRD assessment.
Challenges Ahead
Despite the remarkable progress, the editors and contributing authors consistently emphasize that significant challenges remain unresolved. The optimal integration of MRD testing into clinical workflows, the interpretation of persistent molecular positivity, the timing of sample collection, and the identification of patients who may benefit from treatment escalation or de-escalation all require prospective validation through dedicated clinical trials. Assay standardization, prospective validation, and better definition of clinically actionable thresholds remain prerequisites before widespread implementation into routine practice can be achieved.
The transition from reactive to proactive oncology—where disease can potentially be intercepted before clinical manifestation—represents one of the most important paradigm shifts in modern cancer care, and liquid biopsy stands at the center of this transformation.