TOPLINE:

A blood-based liquid biopsy combining cell-free and exosome-bound microRNAs detected early-onset colorectal cancer (CRC) with strong overall diagnostic performance, high sensitivity for early stages, and efficacy in patients aged 20-35 years.

METHODOLOGY:

• The incidence of early-onset CRC has been rising, but screening uptake among people younger than age 50 years remains low. This international, multicentric cohort study evaluated whether a noninvasive blood test could aid early detection.
• Researchers included 542 participants aged 18-49 years who contributed 621 specimens (503 blood plasma and 118 tissue samples). Patients had histology-proven early-onset CRC, and control individuals were age- and sex-matched and cancer-free with at least 1 year of follow-up.
• They identified six circulating biomarkers (two cell-free, four exosomal) through small RNA sequencing from a biomarker discovery cohort (n = 118) and used them as inputs to create a machine learning model.
• The model was trained on one cohort (n = 192) and tested in an external independent cohort (n = 191). A postsurgery set of samples was used to assess short-term changes in 41 patients.
• Outcomes included diagnostic accuracy assessed using the area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity — overall, stage-wise, and for high-grade dysplasia.

TAKEAWAY:

• The test demonstrated high accuracy in detecting early-onset CRC, with an AUROC value of 97.5% in the training cohort and 95.6% in the external testing cohort. In the testing cohort, sensitivity was 91.6% and specificity was 87.5%.
• Sensitivity was 97.3% for stages I-III (94.1% for stage I, 100% for stage II, and 96.8% for stage III) and 61.5% for high-grade dysplasia. Stage-specific AUROC values ranged from 93.1%-97.4%.
• Performance of the test was consistent across the ages of 18-49 years, even among those aged 20-35 years, with an AUROC of 98.5% in that group.
• In the postsurgery samples, scores fell after curative-intent surgery and often turned negative by day 4.

IN PRACTICE:

"While efforts to improve compliance with endoscopic screening in younger individuals continue, this blood test offers a complementary strategy. It may be a more appealing option for those hesitant about invasive procedures, potentially facilitating and encouraging participation in CRC screening among young adults who might otherwise avoid it," the authors write.

SOURCE:

This study, led by Alessandro Mannucci, MD, Beckman Research Institute of City of Hope, Monrovia, California, was published online December 9 in Gastroenterology.

LIMITATIONS: 

The modest sample size may have led to wide confidence intervals for some stage-specific estimates. The nature of the cohorts made it impossible to evaluate African American patients, a group with high mortality in early-onset CRC. The extracellular vesicle isolation method did not yield pure exosomes, even though it enriched the relevant content for detection.

DISCLOSURES:

This study received grants from the US National Cancer Institute, Istituto de Salud Carlos III, Fight Colorectal Cancer, and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer. The authors acknowledged support from multiple sources including the Zotti Prize, third edition. The authors reported no relevant financial relationships.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.