BLOODPAC: Collaborating to chart a path towards blood-based screening for early cancer detection.

Abstract

Earlier detection of cancer enables intervention when it is more likely to be treatable and curable, resulting in improved patient outcomes, such as the reduction of morbidity and mortality. Analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results data revealed that cancers diagnosed after distant metastasis represent ~18% of all diagnoses and close to half of all deaths.1 Reducing the proportion of cancers diagnosed at late stages is therefore important. Currently, guideline-recommended cancer screening programs vary in convenience, invasiveness, accuracy, adherence, and effectiveness. For example, cervical cancer screening with the Pap test has dramatically reduced mortality from cervical cancer among US women, from 5.55 deaths per 100,000 in 1975 to 2.16 deaths per 100,000 in 2019.2 More recently, the incorporation of molecular human papillomavirus testing increased sensitivity for detection of cervical cancer and allowed for less frequent screening. In contrast, the use of prostate-specific antigen-based tests to screen for prostate cancer has led to challenges related to overdiagnosis and overtreatment without improving overall mortality in a statistically significant manner.3 Recent advances in the understanding of tumor biology and technological innovations in genomics and molecular profiling are enabling development of cancer-associated biomarkers in blood. Analytes of interest include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, proteins, and tumor educated platelets. All have the potential to enable earlier detection of single or multiple cancer types through analysis of a blood sample. Whereas the US Preventive Services Task Force has recommended screening the general population for some cancer types, such as breast and colorectal, for years,4 such screening is not recommended for most cancer types. Blood-based tests, including multi-cancer early detection (MCED) tests, have recently emerged to address this unmet need in cancer screening. Based on lessons learned from existing screening efforts, such tests will require clinical evidence development frameworks that address the tension between proximal (e.g., sensitivity and specificity) and distal (e.g., cancer-specific or overall mortality) end points.5 In the journey from bench to bedside, developers of liquid biopsy technologies need to navigate a host of challenges. The BLOODPAC Consortium was launched on October 17, 2016, as a commitment to the White House Cancer Moonshot to help overcome these challenges and accelerate the development, validation, and clinical use of liquid biopsy tests to better inform medical decisions and improve cancer patient care and outcomes. Consortium members, including diverse stakeholders from industry, academia, government and non-profits, coalesced around a central understanding that no single entity could establish the “infrastructure” needed to bring safe and effective technologies to patients faster. Only a multi-stakeholder collaboration could develop consensus standards and best practices in evidence development necessary to enable clinical implementation of liquid biopsies. Drawing on the consortium's deep multidisciplinary expertise, BLOODPAC has tackled key challenges in the broader liquid biopsy field, addressing critical questions, such as standards for analytical validation and data sharing in genomic testing.6 Today, BLOODPAC consists of over 60 collaborators who recognize that developing frameworks for evidence generation and aggregating data to support those frameworks are two fundamental requirements for success. The consortium's unique and growing footprint in the liquid biopsy landscape signals the success of BLOODPAC in anticipating and addressing the needs of stakeholders. By fostering a culture in which experts can leave their competitive interests at the door and focus on common needs and goals, BLOODPAC has helped to broaden awareness and implementation of recommended standards and guidelines, and thereby enabled the appropriate clinical utilization of safe and effective liquid biopsies. So, why now in 2022, is BLOODPAC focusing on developing standards that can support rigorous evaluation of blood-based screening for early cancer detection? Recent and rapid technological developments in biomarker assays (e.g., next generation sequencing) and data analysis (e.g., artificial intelligence/machine learning) have enabled disruptive approaches to blood-based cancer screening. Furthermore, these innovations are occurring in the context of (1) lessons learned from the COVID-19 pandemic regarding the impact of molecular diagnostics on population health, and (2) renewed focus on ensuring equitable and timely access to healthcare advances. With this publication, BLOODPAC aims to chart both the opportunities and challenges ahead for the clinical use of blood-based tests for screening and early detection in cancer. This emerging field requires stakeholders to align on potential solutions to these challenges and to create standards and frameworks to facilitate the robust and responsible development, validation, and implementation of blood-based cancer screening tests. Although blood-based tests for early cancer detection could materially advance the existing cancer screening paradigm, there remain a number of unsolved challenges. Table 1 describes the challenges and opportunities presented by this new class of tests. In bringing these forward, BLOODPAC seeks to identify areas of focus for the consortium to work with stakeholders to provide evidence-based guidelines and frameworks to help resolve these challenges and, ultimately, advance the field. By working collaboratively to help enable a future in which blood-based screening and early cancer detection can become commonplace, the BLOODPAC Screening and Early Detection Working group seeks to facilitate the implementation of evidence-based screening modalities for cancers with and without effective population screening today. Following the global COVID-19 pandemic, we are at a reflective time as a society and as a healthcare industry. In many ways, the pandemic disrupted our healthcare system and exposed both the barriers and opportunities that exist in cancer care – including the opportunity to harness the power and promise behind new approaches, such as blood-based screening for early cancer detection. It also demonstrated the importance of a public health approach to major health challenges, such as cancer. A blood-based test can make screening and early detection of cancer more accessible and convenient due to the ability of samples to be collected in the setting where individuals typically receive care. This can augment efforts to provide access to cancer screening for people in medically underserved communities. As the use of blood-based tests is increasingly integrated into the cancer care continuum (i.e., cancer detection, diagnosis, treatment, and surveillance), it is important to address the complexities and challenges of these tests to ensure that the potential benefits are quantifiable, with risks clearly elucidated and appropriately mitigated. No single entity can overcome all these challenges. Multi-stakeholder collaboration is critical to advancing this field, and as an established consortium, BLOODPAC has launched the screening and early detection working group to support efforts related to (1) standards and framework development; (2) education; and (3) access and care coordination. These efforts will help a variety of audiences, including supporting the development of safe and effective cancer screening tests by test developers; improving consistency and transparency in regulatory and payer evaluations of these tests; and accurately communicating with patients and providers about their benefits and risks in an effort to accelerate equitable access to these tests for the benefit of society at large. This work will also coordinate with and complement that of others, such as the National Cancer Institute, Cancer Research UK, Friends of Cancer Research, and the MCED Consortium. The BLOODPAC Consortium's mission is to accelerate the development, validation, and accessibility of liquid biopsy tests to improve the outcomes of patients with cancer. The vision of the BLOODPAC 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. Specific goals of the BLOODPAC Screening and Early Detection Working Group will be to (1) develop and socialize a lexicon of standard terms for blood-based assays for the screening and early detection of cancer; (2) develop consensus frameworks that address the tension between proximal (e.g., sensitivity and specificity) and distal (e.g., cancer-specific or overall mortality) end points; and (3) recommend best practices for demonstrating the clinical validity and utility of blood-based early cancer detection tests. The authors acknowledge the contributions to the BLOODPAC Project from Curran Shah from the University of Southern California as well as Donald Johann from the University of Arkansas and Robert Grossman from the University of Chicago for their critical review and thoughtful feedback on the study presented in this manuscript. We also wish to acknowledge the BLOODPAC Executive Committee and Scientific Co-Chairs. Executive Committee: Philip G. Febbo—Senior Vice President and Chief Medical Officer, Illumina; Robert L. Grossman—Professor, University of Chicago CTDS and Founder/Director, Open Commons Consortium; Peter Kuhn—Professor, University of Southern California; Anne-Marie Martin—Senior Vice President and Global Head of the Experimental Medicine Unit in Oncology Research and Development, GlaxoSmithKline; Jake Vinson—Chief Executive Officer, Prostate Cancer Clinical Trials Consortium. Scientific Co-Chairs: Kelli Bramlett—Director of R&D, Thermo Fisher Scientific; Darya Chudova—SVP, Technology, Guardant Health; Jennifer Dickey—Head of Regulatory & Quality, Personal Genome Diagnostics; James H. Godsey—VP, Advanced Dx R&D, Quest Diagnostics; Jerry S.H. Lee—Chief Science and Innovation Officer, Lawrence J Ellison Institute for Transformative Medicine; Hakan Sakul—VP and Head of Diagnostics, Pfizer; Howard I. Scher—Physician and Head, Biomarker Development Initiative at Memorial Sloan Kettering Cancer Center. Funding for this project was provided by the BLOODPAC Consortium and its members. The work described here was done through the BLOODPAC Consortium, which is a not-for-profit consortium consisting of members from industry, academia, not-for-profits, and US Government agencies, including companies that sell liquid biopsy assays, companies that use liquid biopsy assays as companion diagnostics, organizations that do research related to liquid biopsies, organizations that conduct clinical trials involving liquid biopsies, and agencies that develop policies and procedures related to liquid biopsies. In addition, some of the authors are employed by companies in the liquid biopsy field, have stock in companies in the liquid biopsy field, or consult with companies in the liquid biopsy field. The authors worked together collaboratively to develop consensus opinions and the authors do not have any particular or specific conflict with the work described in this paper, beyond those just enumerated. C.A.C. is an employee of GRAIL and Illumina shareholder. G.P. is a former employee an shareholder of Freenome. J.P.B. is an employee and shareholder of Novartis. M.C. is an employee and shareholder of Illumina. N.K. is an employee and shareholder of Novartis. T.M. is a former employee and shareholder of Delfi and an Illumina shareholder as well. M.M. is an employee and shareholder of Pfizer. S.S.B. is an employee and shareholder of EXACT Sciences. Q.Z. is an employee and shareholder of GlaxoSmithKline. All other authors declared no competing interests for this work.