Risk assessment for cancer has typically been approached a single cancer type at a time. This approach helps both elucidate the etiology of each cancer type and assess risk to inform screening guidelines for that individual cancer. Newer technologies have the potential to target detection of several cancers in a single test, and this will require rethinking how we assess risk and inform screening guidelines. Specifically, it will be important to understand the populations who will most benefit from using multi-cancer early detection (MCED) tests and the risk factors associated with risk of developing any cancer to establish MCED screening guidelines.

Multi-Cancer Detection assays have the potential to improve cancer screening by increasing the numbers and types of cancers detected. However, the unknown clinical benefits and harms necessitate the development and conduct of randomized clinical trials to determine clinical effectiveness. This talk will address the issues in trial design for such an RCT using MCD assays for cancer screening and the development of the pilot Vanguard Study.

Stakeholder collaboration is critical for advancing the development and clinical implementation of multi-cancer early detection and screening. The Blood Profiling Atlas in Cancer (BLOODPAC), a nonprofit consortium composed of over sixty organizations within academia, industry, government, and the nonprofit sector, has launched efforts related to standards and framework development, education, and access coordination for MCED. The vision of BLOODPAC’s Screening and Early Detection Working Group includes (1) thinking creatively about how best to evaluate the impact of early detection strategies on morbidity and mortality resulting from rare and currently unscreened cancers; (2) engaging providers and patients in understanding and mitigating the barriers to implementation of blood-based cancer screening tests and provide recommendations for an equitable, resilient, and sustainable healthcare ecosystem that benefits people; and (3) engaging and collaborating with regulatory agencies to generate postmarket evidence to support the safety and effectiveness of blood-based cancer screening tests in real-world use. In this session, we will discuss progress to date on these initiatives, including our soon-to-be-published lexicon of standard terms for blood-based assays for the screening and early detection of cancer.

Key findings from his report Seizing the Transformative Opportunity of Multicancer Early Detection will be presented. Why it’s time for a new cancer screening paradigm in the United States (and globally) and the significant individual, social, and economic benefits that a new approach to multi-cancer early detection (MCED) screening could provide will be discussed, as well as concerns about potential MCED misgivings. How public policy can facilitate greater levels of innovation and deployment of MCED solutions will also be presented.

Screening is currently available for five common cancers. However current screening modalities have limitations with respect to performance in the general population. For these cancers, blood tests for risk assessment have the potential to make screening more efficient by tailoring screening according to risk. For other less common cancers for which population-level screening is not practical, there is a need for blood tests to identify individuals at sufficiently high risk to be screened for these cancers.

Multi-Cancer Early Detection (MCED) testing has the potential to be the paradigm shift needed to enable early detection for more cancers. Harnessing the power of a variety of biomarker classes in MCED test design has been shown to enhance test performance, especially in early-stage detection. We’ll share additional follow-up information from the DETECT - a study and the current data for a novel multi-biomarker class approach to MCED testing that, in combination with standard-of-care screening, may have the potential to detect more cancers at earlier stages when they may be more treatable.

Exosomes are a class of extracellular vesicles that carry multiple, informative signals from DNA, RNA, proteins, and metabolites. They are present in biological fluids such as blood, urine, and saliva. Exosomes are constantly shed from both healthy and diseased cells, making them ideal targets for development of liquid biopsy tests for early disease detection. In this presentation, the CEO of Biological Dynamics, Paul R. Billings, MD, PhD, will review the company's proprietary Alternating Current Electrokinetic (ACE) technology used in their ExoVita exosome-based assays. The ExoVita assays are high-sensitivity and can distinguish between early-stage disease and control patient samples.

A new understanding of the natural history of colorectal cancer (CRC) informs the biological compartments that should be surveyed to develop a classifier for the continuum from advanced adenoma (AA) to CRC. We describe FirstSight, a blood-based multimodal test with a proprietary ‘probability risk function’ classifier that demonstrated high specificity with high sensitivity for CRC and modest sensitivity for AA in a train-test and cross-validation analyzed average risk screening study.

• How well does a cancer test need to perform to be 'disruptive?'
• Are there adaptive approaches to primary screening that may produce benefits in advance of primary population screening?
• What are the key challenges of pan-cancer screening tests?

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 presented.

Cell-free DNA (cfDNA) consists of small nucleic acid fragments entering the bloodstream during apoptosis or necrosis. cfDNA fragmentation patterns detected by low-coverage whole-genome sequencing can be used to detect the presence of circulating tumor DNA (ctDNA) in a background of cfDNA mostly derived from hematologic cells. This presentation will describe the development of a blood-based, whole-genome, next-generation sequencing (NGS) test to detect early stages of cancer in asymptomatic individuals and to follow disease progression in cancer patients being treated with chemotherapy, targeted therapy, or immunotherapy.

The development and implementation of multi-cancer early-detection assays are accompanied by a unique set of challenges. Such challenges include defining an optimal set of biomarkers across multiple cancers, prioritizing performance specific features, and ensuring that the assay is not biased towards specific populations. This talk will address these challenges in the context of all stages of assay development, from development to validation in clinical trials.