Liquid Biopsies, Blood-Based MCED Tests for Detecting CRC in Young Patients

Blood-based multi-cancer detection (MCED) tests and liquid biopsy platforms are unlikely to be integrated into colorectal cancer (CRC) screening strategies for patients under the age of 45 in the near future, according to Yoanna S. Pumpalova, MD. Despite the rising incidence of young-onset CRC, these emerging biomarkers face significant hurdles regarding clinical efficacy and cost-effectiveness when applied to populations currently falling outside standard-risk screening guidelines.

Clinical data from the large-scale NHS-Galleri study (NCT05611632), using the Grail system, serves as a primary benchmark for this assessment. The study was designed to evaluate the utility of MCED tests in a high-risk population to determine if blood-based screening could reduce the detection of stage III and stage IV cancers. However, the trial did not meet its primary end point of decreasing late-stage cancer detection.¹ Investigators did note that a favorable trend was observed toward fewer stage III and IV cancers in a pre-specified group of 12 deadly cancers. Because the test failed to demonstrate this benefit in an older, higher-risk demographic, it is unlikely to be recommended for a younger population where the disease incidence is significantly lower.

Pumpalova noted that the lower prevalence in the under-45 population further complicates the cost-benefit analysis required for widespread deployment. From a societal perspective, the expense associated with deploying these tests broadly for young patients does not currently align with the expected clinical return.

While individual patients may opt to access these tests via out-of-pocket payment, they do not currently fit into a multidisciplinary screening strategy for the young-onset population. The findings from the NHS-GALLERI trial suggest that liquid biopsy technology has yet to prove it can effectively shift the stage of diagnosis at a population level. Consequently, standard-risk screening guidelines are expected to remain focused on established modalities rather than incorporating MCED tests for younger individuals who do not meet traditional risk criteria.

Pumpalova is an assistant professor of medicine and a medical oncologist at the Columbia University Irving Medical Center.

Transcript:

CancerNetwork: Where do liquid biopsies and new biomarkers for early detection fit into a multidisciplinary screening strategy for the “under-45” population who currently fall outside standard-risk screening guidelines?

Pumpalova: Similar to expanding colorectal cancer screening guidelines for young patients, we're probably far from recommending blood-based multi-cancer detection tests for [this group]. The largest study that was recently completed, and we're waiting for final results, is the NHS-Galleri study that took place in the UK using the Grail system to look at multi-cancer detection using blood-based tests. That study did not meet its primary end point of decreasing stage III and stage IV colorectal or any cancer detection, and that's in a higher-risk population.

Even though young-onset colorectal cancer is increasing in incidence, it is still a small proportion of the total colorectal cancers that we see, and age is still one of the strongest risk factors for developing [the disease]. [Considering] the fact that the test didn't meet its primary end point in that higher-risk older population, it's unlikely that it will be recommended or applied for that younger population, where the incidence is lower. There will be people who choose to pay for that test out-of-pocket, and that's fine, but from a societal and cost perspective, it's unlikely that it will be cost-effective to deploy that test widely for young patients.

Reference

1. Landmark NHS-Galleri trial demonstrates a substantial reduction in stage IV cancer diagnoses, increased stage I and II detection of deadly cancers, and four-fold higher cancer detection rate. News release. GRAIL. February 19, 2026. Accessed March 19, 2026. https://tinyurl.com/3kmyxwcp