Multi-cancer early detection (MCED) tests show promise as cancer screening tools. However, rigorous evaluation, preferably in a randomized-controlled trial (RCT), is necessary to prove their clinical utility. Due to the novel nature of MCED tests, several issues need to be resolved before embarking on a large-scale, definitive RCT of MCEDs. For that purpose, the NCI is planning on launching a pilot trial to try to resolve these issues.

A targeted methylation-based MCED detects a shared cancer signal across many cancer types with a low false positive rate, and predicts the cancer origin to direct downstream diagnostic work-ups. The performance of this MCED as well as appropriate performance metrics specifically for multi-cancer tests, the underlying biology of the signal that results in a balance of detecting more aggressive cancers while minimizing the risk of over-diagnosis, and the potential impact of implementing MCEDs in conjunction with standard-of-care cancer screening will be discussed.

The MCED Consortium, a group of volunteers, advisors, and companies spanning a wide range of expertise in biomarker evaluation and implementation, with a special focus on clinical practice, health equity, and communication, are developing recommendations for the evaluation of test utility, appropriate population targets for screening or early detection, downstream actions in health systems, issues of health equity, and communication challenges related to this new, potentially revolutionary generation of tests.

The speaker will address the varied needs of different cancers for liquid biopsy tests in early detection, with special emphasis on risk assessment. Important need for cancers for which screening is currently an option, is a personalized risk profile based on a combination of biomarkers and subject characteristics that would allow tailoring of screening according to risk. For other less common cancers for which screening in a general population setting is not practical, liquid biopsy tests would offer the opportunity to identify individuals at sufficiently high risk to initiate surveillance.

Much interest has emerged in multi-cancer early detection. However, such MCED tests are not conceived to replace current cancer screening modalities. The challenge of how to reconcile single-cancer vs multi-cancer screening will be addressed.

Liquid biopsies are sources of biomarkers that provide early detection of cancer often prior to metastatic spread. The newer technologies reveal the tissue of origin primarily via measurement of methylation patterns. This talk will review the remaining challenges for further development, including studies to establish standards using the various analytes and use of the biomarker results. A review of recent data emerging from the many international studies will be provided.

Tests that can detect multiple cancers with a single blood draw are fast becoming a reality. Diagnostic performance studies indicate that these tests can identify some cancers early but the implications for population health remain unclear. Lessons learned from decades of early detection research can help to manage expectations and guide strategies for test evaluation in a new era of novel cancer diagnostics.

Multi-cancer early detection assays are available from multiple companies but adoption in the USA/Europe may lag due to integration and competing existing systems; however, implementation in emerging economies where little infrastructure exists could have an immediate impact on morbidity and mortality. Engaging governments, academia, and industry partners to deploy, test, and validate these assays in low resources settings will leapfrog systems to a higher level of cancer care.