Applications of Liquid Biopsy for Surgical Patients With Cancer

Abstract

ImportanceLiquid biopsy is an emerging tool with the potential to change oncologic care practices. Optimal clinical applications for its use are currently undefined for surgical patients.ObservationsLiquid biopsy analytes such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been the most clinically studied assays and were initially limited to advanced-stage disease. In the metastatic setting, CTCs and ctDNA levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. Technological advancements in assay sensitivity have expanded the use of ctDNA to early-stage and resectable disease, allowing for detection of minimal residual disease. Postoperative ctDNA levels are a strong predictor of disease recurrence, and ctDNA detection often precedes serum carcinoembryonic antigen elevation and radiographic changes. However, its use for surveillance has not been shown to improve clinical outcomes. A promising application of ctDNA is for adjuvant therapy escalation and de-escalation. A phase 2 clinical trial demonstrated that treatment de-escalation for patients with high-risk stage II colorectal cancer and negative postoperative ctDNA had similar recurrence-free survival as patients receiving standard-of-care chemotherapy. These results suggest that ctDNA may help select patients who will benefit from adjuvant chemotherapy, and multiple clinical trials are actively underway.Conclusions and RelevanceAlthough uncertainties regarding the optimal use of liquid biopsy remain, it has the potential to significantly improve care for patients with cancer at all stages of disease. It is critical that surgeons understand how to use and interpret these assays, and they should be active participants in clinical trials to advance the field.

Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans

“…In another study including 1220 oncologists who discussed genomic testing with patients, 50.0% reported often discussing the likely costs of testing and related treatments and 26.3% reported sometimes discussing costs . However, ctDNA testing is already in the clinic and increasingly being used . Most oncologists surveyed showed interest in using ctDNA testing in ACT decision-making for patients with colon cancer, and in a study of patient-reported outcomes from the BESPOKE trial, most patients surveyed said that they valued the ctDNA testing information and would continue ctDNA testing.…”

“… 26 However, ctDNA testing is already in the clinic and increasingly being used. 27 Most oncologists surveyed showed interest in using ctDNA testing in ACT decision-making for patients with colon cancer, 28 and in a study of patient-reported outcomes from the BESPOKE trial, 29 most patients surveyed said that they valued the ctDNA testing information and would continue ctDNA testing.…”

Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis

“…In the past decade, a growing interest has emerged in the application of liquid biopsies (LB) as a conceptual strategy to meet above mentioned need. LB represents a noninvasive methodology capable of furnishing crucial diagnostic, therapeutic, and prognostic information across various cancer types 8 – 11 . Within the realm of liquid biopsy, circulating tumor DNA (ctDNA) is released from apoptotic cancer cells and manifests in diverse proportions within cell-free DNA (cfDNA) 12 , 13 .…”

Cell-Free DNA: Unveiling the Future of Cancer Diagnostics and Monitoring

“…In recent years, cfDNA analysis has evolved from a blurred hypothesis to a tangible and reliable clinical tool. Its non-invasive nature, accessibility, and dynamic reflection of tumor evolution offer a stark contrast to traditional tissue biopsies [1][2][3]. Several preclinical and clinical studies have explored the use of cfDNA as an early detector of cancer.…”