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Liquid biopsies offer faster and more accurate biomarker identification for bowel cancer patients

Written by Poppy Jayne Morgan

A new study in ESMO Open has identified a faster and more accurate diagnosing tool that can help clinicians optimise treatments for bowel cancer patients.

Researchers at the Hospital Universitario Virgen de la Victoria in Spain have compared liquid biopsy techniques to standard of care tissue testing to improve biomarker identification that can be used in clinical settings. The adoption of non-invasive liquid biopsies could identify guideline-recommended biomarkers accurately and within a quicker timeframe than current tissue-based tests.

Vital genotyping

Complete genotyping in bowel cancers is essential in the selection of optimal first-line therapy. However, the authors raised that “despite guideline recommendations, incomplete genotyping is rampant and often results in unsuitable treatment, leading to lack of benefit and premature disease progression.”

International cancer organisations, including the European Society for Medical Oncology and the National Comprehensive Cancer Network, recommend using next-generation sequencing to test for mutations in suspected or confirmed colorectal cancer patients. However, this is often incomplete, either due to long wait times, a lack of available tissue samples or inaccurate tests that give false negatives. Subsequently, patients may begin therapy before biomarker results are available, meaning they might not be on the right treatment plan in the first stage.

“Without comprehensive testing, patients risk receiving suboptimal treatment, resulting in poorer outcomes, and may also suffer from complications associated with unsuitable therapies”, the authors noted.

Metastatic colorectal cancer is where cancer cells may break away from a tumour in the colon or rectum and spread to other parts of the body through the bloodstream or lymphatic system. Colorectal cancer is the third most common cause of cancer mortality worldwide. 20% of patients have metastatic disease at presentation, and another 25% who present with localised disease will later develop metastases.

Biomarker tests that are faster and more accurate could help cancer patients receive suitable treatments quicker and help clinicians identify the best therapy options. 

The non-invasive biomarker alternative: ctDNA

Circulating tumour DNA (ctDNA) testing has emerged as an alternative to standard of care (SOC) tissue testing. ctDNA liquid biopsies measure circulating tumour cells or cell-free DNA in bodily fluids, providing a non-invasive technique to monitor and detect cancers with in-depth molecular information.

The researchers wanted to identify if the adoption of ctDNA testing into clinical practice had the potential to improve the care of bowel cancer patients.

Patients with previously untreated metastatic colorectal cancer (mCRC) who were undergoing SOC tissue genotyping submitted pre-treatment blood samples for comprehensive circulating tumour DNA (ctDNA) analysis.

Over 150 mCRC patients participated in the study and ctDNA identified a guideline-recommended biomarker in 56.8% of patients, while SOC tissue genotyping identified 52.9%. Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5%, by improving those without tissue results either due to tissue insufficiency, test failure, or false negatives. 

Furthermore, ctDNA rapid turnaround time was significantly faster than tissue testing. In this study, comprehensive ctDNA analysis improved identification of patients with guideline-recommended actionable biomarkers in the 2 weeks after sample collection, which is a key period when decisions regarding treatment are most often made.

Despite rapid and relatively complete biomarker discovery, a minority of patients (6.5%) were identified by tissue but not comprehensive ctDNA testing, and a similar minority (10.3%) were identified by ctDNA but not tissue testing. The authors suggested that using both testing modalities simultaneously would maximise the opportunity for biomarker discovery.

The authors reported, “we demonstrate that comprehensive ctDNA testing identifies at least as many patients with guideline-recommended biomarkers as SOC tissue testing and does so in a shorter time.” This will allow informed treatment choices without subjecting patients to delay.

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