Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

Abstract

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts’ about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.

Clinical Validity of Circulating Tumor DNA as Prognostic and Predictive Marker for Personalized Colorectal Cancer Patient Management

“…Besides ctDNA, other LB analytes including circulating tumor cells (CTCs) have also been investigated for clinical application. Whereas CTCs allow the extraction of detailed information at the single cell level [6,7], numerous studies have shown that ctDNA profiles are highly concordant with the molecular profile of primary tumors and metastases [8,9], and are considered to have a higher likelihood to enter clinical application [10]. Since CTCs and ctDNA are analytes present in LB, the advantages of LB, such as non-invasiveness and ease of repeatability, enable CTC and ctDNA analysis independently of the patient's condition and at any desired time point [11][12][13].…”

Development and Validation of a Targeted ‘Liquid’ NGS Panel for Treatment Customization in Patients with Metastatic Colorectal Cancer

“…Despite the clinical value of ctDNA testing, there is a plethora of challenges regarding the cost and implementation of liquid biopsy tests in a clinical laboratory [ 46 ]. Keeping this in mind, we developed a targeted, easy-to-use NGS assay for the monitoring of patients with mCRC.…”

Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells

“…A multi-marker-based system is believed to permit the enrichment of a wider subset of CTCs, including phenotypes of epithelial, mesenchymal, and those transitioned in between. Nevertheless, additional large-scale studies in high-risk groups and the further under-standing of their biology and significance could enhance CTCs' utility as a blood-based biomarker [163]. Finally, a real gap exists between the genuine attraction of obtaining a large number of publications in this domain and its application into routine clinical practice.…”

“…Furthermore, the lack of large-population follow-up cohort studies increases the difficulties of translating current CSM-based CTC detection methods into the clinical setting for CRC screening, diagnosis, prognosis, real-time monitoring, and therapeutic response [50][51][52][53][54]. Other reasons include (i) the vast number of methods described for potential CTC detection (including the pre-analytical, analytical, and postanalytical phases), without a consensus on the ideal/standardized technical approach; (ii) difficulty in controlling the pre-analytical phase to obtain robust and reproducible results; and (iii) the high cost of the currently available techniques [162,163].…”