Eur J Cancer. 2025 Dec 9;231:116050. doi: 10.1016/j.ejca.2025.116050. Epub 2025 Oct 20.

ABSTRACT

BACKGROUND: Circulating tumor cells (CTCs) are a versatile biomarker in solid tumors. Extensive research supports their clinical relevance and led to regulatory approval in breast, prostate, and colorectal cancers. However, clinical adoption remains limited mainly due to the lack of consensus and standardized technologies. Additionally, CTC research lacks unified direction. To address these gaps, an international expert panel was established to assess the current and future clinical utility of CTCs.

METHODS: A panel of 11 CTC experts identified key areas of controversy, informing a structured survey distributed to 55 international multidisciplinary experts. Consensus was predefined as ≥ 70 % agreement. Areas without consensus were discussed in a virtual meeting, leading to final statements on the clinical integration of CTCs.

RESULTS: Thirty-seven experts completed the survey. Consensus was reached on the clinical utility of CTCs for prognosis and treatment monitoring in metastatic breast (BC) and prostate (PC) cancers, including AR-V7 testing in metastatic castration-resistant PC for therapy selection. In other tumors, CTCs remain investigational. Experts agreed that while clinical utility is not yet established in early-stage disease, CTCs show promise in early BC, especially combined with cell-free DNA (cfDNA) for minimal residual disease detection. CellSearch® is currently the only platform with high-level evidence for clinical use, though emerging technologies are promising. Key challenges include improving detection sensitivity/specificity, standardizing workflows, generating robust data, and clinician education. Experts emphasized shifting from enumeration to phenotypic and molecular characterization, particularly for treatment guidance, and highlighted the complementary role of CTCs and cfDNA, advocating for integrated liquid biopsy approaches.

CONCLUSIONS: This consensus offers practical guidance for clinical integration of CTCs and outlines strategic research priorities to unlock their full potential in precision oncology.

PMID:41172567 | DOI:10.1016/j.ejca.2025.116050

Expert Rev Mol Diagn. 2025 Jun;25(6):263-274. doi: 10.1080/14737159.2025.2498545. Epub 2025 Apr 28.

ABSTRACT

INTRODUCTION: In recent years, circulating tumor DNA (ctDNA) has emerged as a promising method for detection of minimal or molecular residual disease (MRD) among patients with breast cancer.

AREAS COVERED: In this narrative review, we provide a summary of currently available studies assessing use of ctDNA in detection of MRD in patients after completion of curative therapy. Additionally, we discuss limitations of present studies, future considerations, and an overview of ongoing trials evaluating the clinical utility of MRD-directed therapy interventions.

EXPERT OPINION: While the clinical utility of MRD-directed therapy guidance remains under investigation, collective data from studies overwhelmingly confirm the prognostic value of ctDNA status across various stages and subtypes of breast cancer. Results from ongoing clinical trials in the coming years will provide more clarity on the overall clinical benefit of MRD-directed interventions for breast cancer patients.

PMID:40288891 | DOI:10.1080/14737159.2025.2498545