Cancer Epidemiol Biomarkers Prev. 2026 Apr 1;35(4):491-493. doi: 10.1158/1055-9965.EPI-25-1971.

ABSTRACT

Recently, stool- and blood-based cancer screening kits have been approved in clinical practice as convenient and noninvasive methods for colon cancer screening. One such test in long-standing practice has included the fecal immunochemical test (FIT), wherein home-based testing has rendered it a convenient initial assay to complement screening colonoscopy, despite limitations in diagnostic performance. In a recent original study published in the journal by Nguyen and colleagues, the feasibility and performance of combining FIT with circulating tumor cell (CTC) enumeration for predicting colorectal neoplasia and the risk of developing colorectal cancer were described. In this commentary, we highlight the potential of this combination as a novel colorectal cancer screening technique. The introduction of CTC as a potential colorectal cancer screening assay is timely, given the emergence of liquid biopsies that hold promise in their ability to detect a multitude of cancer-specific signals, from the detection of minimal residual disease to the detection of molecular alterations for precision therapies in oncology. We place the importance of their results in the context of the evolving landscape of stool- and blood-based colorectal cancer screening tests involving multitarget fecal DNA and cell-free DNA assays. See related article by Nguyen et al., Cancer Epidemiol Biomarkers Prev 2026;35:79-87.

PMID:41918361 | DOI:10.1158/1055-9965.EPI-25-1971

Cancer Biol Med. 2026 Mar 30:j.issn.2095-3941.2026.0045. doi: 10.20892/j.issn.2095-3941.2026.0045. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) remains a major global health burden characterized by late-stage diagnosis and high postoperative recurrence rates. This review presents a surgery-centered precision management framework integrating 3 synergistic components: early detection, precision surgery, and recurrence prevention. Early detection strategies incorporate multiparameter risk models including the gender, age, AFP-L3, AFP, and DCP (GALAD) as well as age, sex, AFP, and PIVKA-II (ASAP) scores, alongside circulating tumor DNA methylation-based liquid biopsy, thus enabling tumor identification at stages amenable to curative resection. Precision surgery optimizes patient selection through refined staging systems including the Chinese liver cancer staging (CNLC), and functional assessments including the albumin-bilirubin (ALBI) grade, whereas conversion therapy and minimally invasive approaches extend surgical eligibility to selected patients with intermediate-stage disease. To mitigate the risk of postoperative recurrence, distinguishing between early and late recurrence patterns and monitoring minimal residual disease are critical strategies. Perioperative systemic therapies, particularly immune checkpoint inhibitor-based combinations, show promise for eradicating micrometastatic disease. This integrated framework provides a cohesive, evidence-based approach to personalized HCC management aimed at maximizing curative potential and long-term survival.

PMID:41913379 | DOI:10.20892/j.issn.2095-3941.2026.0045

Oncologist. 2026 Mar 30:oyag108. doi: 10.1093/oncolo/oyag108. Online ahead of print.

ABSTRACT

Pancreatic cancer remains one of the most lethal malignancies, with limited integration of precision oncology into routine clinical care. We present a unique case of a RAS wild-type, MSI-H, TMB-H pancreatic ductal adenocarcinoma harboring a TPM3-NTRK1 fusion, monitored through 13 serial liquid biopsies over 3 years. Dynamic changes in NTRK1-fusion allele frequency, tumor mutational burden, and the emergence of an NTRK1 resistance mutation guided finely tuned, situation-adapted therapeutic adjustments: rapid disease control with targeted NTRK inhibition followed by durable remission under immune checkpoint blockade. This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context- driven treatment strategies in rare molecular subtypes of pancreatic cancer.

PMID:41913057 | DOI:10.1093/oncolo/oyag108

Clin Transl Oncol. 2026 Mar 30. doi: 10.1007/s12094-026-04334-4. Online ahead of print.

ABSTRACT

Cholangiocarcinoma (CCA), particularly the IDH-mutant subtype, presents major clinical challenges because it is frequently diagnosed at an advanced stage and carries a high risk of postoperative recurrence. Detecting minimal residual disease (MRD) is crucial, as it enables early identification of patients at high risk of relapse, guiding personalized adjuvant therapy to prevent recurrence and improve survival. Standard imaging modalities are unable to reliably detect microscopic MRD. In contrast, circulating tumor DNA (ctDNA) has emerged as a promising, non-invasive biomarker for MRD detection in IDH-mutant CCA, supported by the strong concordance between IDH1/2 mutations identified in tumor tissue and those found in plasma. Current first-line therapy for advanced IDH1-mutant disease includes gemcitabine plus cisplatin combined with either durvalumab or pembrolizumab. Ivosidenib is commonly used as a second-line targeted therapy. ctDNA dynamics, such as persistent postoperative or post-chemotherapy positivity or rising levels during treatment with IDH inhibitors, are associated with poorer disease-free and overall survival. Despite its promise, ctDNA-based MRD assessment faces significant biological and technical limitations, including clonal hematopoiesis, low ctDNA fractions in body fluids, high technical costs, and the absence of standardized thresholds. More prospective clinical trials are needed to validate ctDNA-guided risk stratification, support treatment decisions on adjuvant therapy escalation or de-escalation, and enable treatment adaptation in IDH-mutant CCA, ultimately advancing precision oncology beyond the capabilities of imaging alone. This review aims to evaluate the potential of ctDNA-based MRD detection to refine precision treatment strategies in IDH-mutant CCA.

PMID:41912863 | DOI:10.1007/s12094-026-04334-4

Cancer Sci. 2026 Mar 30. doi: 10.1111/cas.70368. Online ahead of print.

ABSTRACT

This study evaluated the feasibility of urinary extracellular vesicles (EVs) as a liquid biopsy source for colorectal cancer (CRC) using two predefined cohorts: 97 patients for analytical validation and 63 patients for postoperative survival analysis. We compared urinary EVs, urinary cell-free tumor DNA (ctDNA), plasma EVs, and plasma ctDNA across multiple molecular dimensions, and assessed the utility of urinary EV-DNA for minimal residual disease (MRD) detection. Urinary EVs exhibited larger particle size (median 175.6 nm) and markedly higher purity, demonstrated by a substantially broader proteomic profile (4674 vs. 476 proteins) and significantly higher expression of EV-specific markers (CD63, CD81, CD9). DNA extracted from urinary EVs showed the highest concentration and best preservation of nucleic acid integrity, with the greatest Long/Short fragment ratio, outperforming all plasma-derived samples. Mutation detection sensitivity was comparable across sample types but was highest in plasma ctDNA (39.2%) and urinary EV-DNA (34.0%), exceeding urinary ctDNA (21.6%). In the survival cohort, MRD positivity-defined as detectable RAS/BRAF mutations in urinary EV-DNA 1 month after curative surgery-was strongly associated with inferior outcomes (HR for recurrence 5.25, 95% CI 1.74-15.80), and overall survival was significantly worse in MRD-positive patients. These findings indicate that urinary EVs provide highly pure vesicles with superior DNA quality, making them a robust and completely non-invasive source for molecular profiling. Urinary EV-DNA-based MRD assessment shows significant prognostic value and may serve as a practical tool for postoperative monitoring and risk stratification in colorectal cancer.

PMID:41906796 | DOI:10.1111/cas.70368

Surg Oncol Clin N Am. 2026 Apr;35(2):399-414. doi: 10.1016/j.soc.2025.12.010. Epub 2026 Feb 6.

ABSTRACT

Liquid biopsies offer a promising, noninvasive approach for monitoring and predicting responses to immunotherapy across multiple solid tumors. For the most part these are circulating tumor DNA (ctDNA) based assays. Here, we discuss the biological basis, clinical evidence, and potential applications of different types of ctDNA assays in tracking tumor dynamics, distinguishing pseudoprogression, and assessing minimal residual disease. We explore the current limitations, assay variability, and future directions, including integration with other biomarkers and real-world clinical trials aimed at validating ctDNA as a routine tool in precision immuno-oncology.

PMID:41903996 | DOI:10.1016/j.soc.2025.12.010

J Thorac Oncol. 2026 Mar 26:103696. doi: 10.1016/j.jtho.2026.103696. Online ahead of print.

ABSTRACT

INTRODUCTION: Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early-stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation.

METHODS: The Asian Thoracic Oncology Research Group (ATORG) convened a multi-disciplinary panel of 27 experts to develop a consensus statement on the clinical application of ctDNA-based MRD testing in early-stage resected NSCLC, using a structured Delphi methodology. Statements were organized into broad thematic domains: Assay validity and standardization; Harmonization in research and trials; Clinical application; Challenges in implementation; Consensus recommendations; Infrastructure for regional MRD adoption; and Roadmap for pragmatic trials.

RESULTS: A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling timepoints and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. While current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes.

CONCLUSION: These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

PMID:41903701 | DOI:10.1016/j.jtho.2026.103696

Int J Mol Sci. 2026 Mar 20;27(6):2847. doi: 10.3390/ijms27062847.

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is biologically and clinically dichotomous according to HPV status, a distinction that fundamentally dictates the design, implementation, and interpretation of liquid biopsy strategies. Conventional anatomical imaging lacks sufficient sensitivity for minimal residual disease (MRD) detection, contributing significantly to treatment failure and suboptimal clinical outcomes. This review provides a critical, evidence-based synthesis of the three principal circulating analytes, circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), and their evolving roles in real-time, non-invasive molecular monitoring. Critically, the clinical readiness of these analytes differs substantially: while ctDNA, particularly HPV-related ctDNA, is approaching clinical validation for MRD detection and recurrence surveillance in HPV-positive HNSCC, exosomes and CTCs remain investigational tools hindered by ongoing technical challenges including lack of standardized assays, limited reproducibility across platforms, and insufficient prospective validation. We review how the presence of a clonal, virally derived DNA target in HPV-positive HNSCC contrasts with the heterogeneous somatic mutational landscape of HPV-negative tumors, necessitating divergent analytical platforms and yielding distinct clinical utility profiles for MRD detection and recurrence surveillance. We further outline a pragmatic translational pathway focused on assay standardization, particularly for exosomes and CTCs where this foundational work is most urgently needed, integration of complementary multimodal liquid biopsy approaches, and rigorously designed prospective interventional clinical trials to establish clinical utility. Collectively, these efforts aim to transition HNSCC management from reactive, anatomy-based surveillance to proactive, molecularly guided precision oncology, with the potential to improve therapeutic decision-making and patient outcomes.

PMID:41898706 | PMC:PMC13027142 | DOI:10.3390/ijms27062847

Crit Rev Oncol Hematol. 2026 Mar 25;222:105300. doi: 10.1016/j.critrevonc.2026.105300. Online ahead of print.

ABSTRACT

INTRODUCTION: Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancy, with a high rate of recurrence due to minimal residual disease (MRD). Traditional surveillance methods have limited sensitivity for detecting MRD. ctDNA has emerged as a promising biomarker for real-time tumor monitoring and early detection of MRD.

METHODS: We performed a systematic search of Medline, Embase, and CENTRAL through July 2025. Eligible studies included cohort studies involving adults with EOC that reported ctDNA data, collected post-surgery or after adjuvant chemotherapy. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were extracted and stratified by ctDNA status (detectable vs. undetectable). All statistical analyses were performed at Review Manager version 5.4. This study is prospectively registered in PROSPERO (CRD420251124631).

RESULTS: A total of 1291 records were identified, of which 11 studies met eligibility criteria, encompassing 627 patients with EOC. The pooled analysis showed that ctDNA positivity after surgery was significantly associated with worse PFS (HR 3.83; 95% CI 2.55-5.77; I²= 5% p < 0.01) and OS (HR 2.84; 95% CI 1.22-6.57; I²=0; p < 0.01) compared with ctDNA-negative patients. Similarly, post-adjuvant chemotherapy detection of ctDNA yields worse PFS (HR 4.95) and OS (HR 5.95).

CONCLUSION: Our findings suggest that ctDNA is a novel instrument for MRD detection, and its presence serves as a potent prognostic indicator for recurrence and mortality in ovarian cancer. These results support integrating ctDNA into clinical trial designs and highlight its potential for risk-adapted surveillance and treatment strategies.

PMID:41895358 | DOI:10.1016/j.critrevonc.2026.105300

Med Sci (Basel). 2026 Mar 5;14(1):123. doi: 10.3390/medsci14010123.

ABSTRACT

Measurable residual disease (MRD) has become a central determinant of prognosis and treatment planning in acute myeloid leukemia (AML). MRD assessment is now aided by a wide range of technologies, including next-generation sequencing, PCR-based assays, multiparameter flow cytometry, and emerging approaches such as liquid biopsy platforms and imaging-based detection. These modalities differ in sensitivity, applicability, and interpretive framework, yet each offers distinct advantages in specific disease contexts. Beyond technical issues, MRD is becoming increasingly integrated into clinical practice. In non-intensive treatment settings, where targeted and low-intensity regimens rely on dynamic disease monitoring to guide ongoing management, MRD is increasingly being used to inform therapeutic decisions. In the peri-transplant setting, MRD status influences conditioning strategies, donor selection, and the use of post-transplant interventions. Despite the growing evidence supporting the clinical relevance of MRD across these scenarios, challenges remain regarding standardization, optimal timing of assessment, and the interpretation of discordant results. This review summarizes the full landscape of MRD detection methods and examines the evolving role of MRD in contemporary AML management, emphasizing current applications and areas requiring further refinement.

PMID:41892838 | PMC:PMC13028118 | DOI:10.3390/medsci14010123

Expert Rev Mol Diagn. 2026 Mar 30:1-4. doi: 10.1080/14737159.2026.2651162. Online ahead of print.

NO ABSTRACT

PMID:41891713 | DOI:10.1080/14737159.2026.2651162

Res Sq [Preprint]. 2026 Mar 18:rs.3.rs-8913641. doi: 10.21203/rs.3.rs-8913641/v1.

ABSTRACT

Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA⁺, GPRC5D⁺, and CD319⁺ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA⁺ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319⁺ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.

PMID:41890853 | PMC:PMC13015583 | DOI:10.21203/rs.3.rs-8913641/v1

Cancer Manag Res. 2026 Feb 6;18:574678. doi: 10.2147/CMAR.S574678. eCollection 2026.

ABSTRACT

Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with a rising global incidence and few therapeutic options for advanced disease. In recent decades, precision oncology for CCA has advanced rapidly, particularly through the development of targeted therapies for patients with actionable genetic alterations. These therapies have markedly prolonged survival and improved other clinical outcomes among patients with unresectable, advanced CCA. The implementation of precision oncology largely depends on detecting genetic mutations to guide patient selection and treatment, using tumor tissue biopsies or liquid biopsies, including circulating tumor DNA (ctDNA) from blood or bile. As a minimally invasive biomarker, ctDNA shows great promise for transforming the clinical management of CCA. This review provides a comprehensive overview of the roles of ctDNA in CCA, including early detection, prognostic stratification, minimal residual disease assessment, recurrence monitoring, therapeutic target identification, and treatment response evaluation. A synthesis of existing studies indicates that bile-derived ctDNA shows superior sensitivity compared with blood-based ctDNA in capturing the genetic profiles and heterogeneity of CCA. We also propose an integrative framework that illustrates how ctDNA profiling can inform diagnosis, treatment, and surveillance across the disease continuum. Because research on ctDNA in CCA remains in its infancy, we discuss current challenges and outline future directions for translating these findings into clinical practice. Collectively, the evidence positions ctDNA-particularly bile-derived ctDNA-as a dynamic tool for real-time genomic profiling, sensitive residual disease detection, and therapy monitoring. This integrative framework provides a roadmap for translating these capabilities into clinical practice, with the potential to enable earlier, more personalized interventions and improve outcomes for patients with CCA.

PMID:41883993 | PMC:PMC13012645 | DOI:10.2147/CMAR.S574678