Novel Multicancer Early Detection Technology––Potential Value to Employers and the Workforce

Cancer is soon to become the world’s leading killer. Despite significant advances in therapeutics and guideline-recommended tests that screen for 5 cancer types—a single cancer at a time—cancer kills nearly 1700 of our loved ones every day in the United States.¹ The fact remains that even today, the majority of cancers still lack screening tests and are therefore detected too late and often not impacted by available therapies, leading to poor patient outcomes.

in developing novel therapeutics, these mortality numbers are simply unacceptable. As such, we believe the best chance at reducing cancer mortality is to increase focus on cancer prevention and early detection. Because age is an established risk factor for many malignancies, there may be a misperception that cancer is a disease of the elderly; however, cancer strikes all age groups.

Cancer is a disease that strikes great fear in many individuals, but it is also a disease of interest and concern for the self-insured and employers. Employers have a bigger stake in the health of their employees, employees’ families, and employee productivity than any other entity or institution in our society. As they balance strategies to optimize the health of their employees and beneficiaries while constraining growth in health care costs, employers find cancer represents a substantial challenge. This complexity relates to many factors, including a dearth of data on quality of care, as well as a lack of price transparency. These factors are magnified by the fact that the term “cancer” translates into hundreds of specific clinical scenarios, compared with hypertension or diabetes, with each having an extensive array of services needed to support employees and their families when faced with a cancer diagnosis.

Cancer is among the top diagnoses in terms of the number of claims and the total cost of treatment. In 2018 alone, there were 12 claims over $3 million, and 4 were driven by cancer-related treatments.² Additionally, cancer was the most common million-dollar claim category for ages 40 to 59.² Out-of-pocket costs for cancer treatments, including surgical procedures, radiation treatment, and chemotherapy totaled a whopping $5.6 billion in the United States in 2018.³ Not surprisingly, for the past several years, cancer has continually topped the list as both the number 1 and number 2 highest-cost claim conditions, accounting for 26.8% and $936.3 million of the total stop-loss reimbursements.²

“Financial toxicity, ” which refers to the negative impact of rising out-of-pocket costs on patients’ physical and financial well-being, is well documented across numerous cancer diagnoses. Prospects to mitigate these cost pressures are bleak in that overall cancer costs continue to rise. The US expenditure on cancer-related health care is projected to increase from $183 billion in 2015 to $246 billion in 2030—an increase of 34%. These high costs are paid by people with cancer as well as their families, employers, insurance companies, and taxpayer-funded public programs like Medicare and Medicaid.⁴

The direct costs of cancer care can be superseded by the indirect costs resulting from lost productivity.⁵ Estimates suggest that indirect costs represent the greatest proportion of total cancer costs to an employer in certain clinical circumstances, largely due to short-term and long-term disability.⁵ Cancer also contributes significantly to early retirement and premature death.⁵

We have made great strides in the development of cancer therapeutics, particularly with specialty pharmaceuticals, but this has led to a parallel increase in cost. Notably, within the top 20 highest-cost injectable drugs, 71% of the spending was related to medications used to treat cancer. Furthermore, all of the top 5 highest-cost injectable drugs and 8 of the top 10 were drugs most commonly used in cancer treatment.² Employers have expressed a substantial interest in better understanding how to improve the quality and reduce the cost of treatment once a diagnosis is made.⁵ This prompts us to ask: What if cancer diagnoses were made early enough to have treatments lead to superior patient-centered outcomes and more efficient health care spending?

Early detection of cancer can undoubtedly save lives, yet most cancers are diagnosed too late. It is well recognized that cancers diagnosed at earlier stages have dramatically better 5-year cancer-specific survival than cancers diagnosed after distant metastases.⁶ Even so, screening is currently recommended for only 5 types of cancers in the Unites States: breast, colorectal, cervical, lung (for high-risk individuals only), and prostate (on an individualized basis). Due to the lack of screening programs for other cancers, they are typically identified at advanced stages when outcomes are poor. Thus, these cancers without currently available screening tests account for about 71% of US cancer deaths among those aged 50 to 79 years old.^1,7

There is a misconception that we don’t screen for these cancers because treatments are unavailable. However, a review of evidence-based practice guidelines and peer-reviewed literature shows that nearly all early cancers have effective treatments, including watchful waiting for some non-aggressive malignancies such as early prostate cancers.

A paradigm shift in early detection of cancer is needed to impact the outcomes in patients’ lives. So, what if we were to transition from screening for individual cancers to screening individuals for all possible cancers? This could dramatically improve overall cancer detection, or the Cancer Detection Rate (CDR), in a population.

CDR is the overall number of cancers detected out of the total number of expected cancers in a monitored population. In the United States, for example, there will be an estimated 1.2 million cases of cancer in adults between the ages of 50 to 79 this year; mammography is expected to detect 114,000 of those 1.2 million cancers, yielding a CDR of approximately 9%. A combination of all 5 single-cancer screening tests will yield a CDR of only approximately 16%.^8,9 Although this is a notable accomplishment, it will not suffice by itself to bend the cancer mortality curve or address the public health crisis posed by cancer.

Rapid and significant advancement in genomic technologies shows great promise to develop a solution for the inability to diagnose a greater proportion of cancer cases. There are several novel multi-cancer early detection (MCED) tests nearing commercial availability.^10-12 These MCED tests use sophisticated technologies to identify signals of early cancer in blood and can detect a variety of cancers, many of which are potentially lethal and currently have no recommended screening tests. The ease and convenience of cancer detection via a single blood draw is an important added advantage that could help achieve better compliance than existing single-cancer screening tests. Still, the goal is not to have an MCED test replace the current cancer screening paradigm, but rather to complement existing single-cancer screening tests.

An MCED test could easily be integrated during preventive care visits or routine blood tests, which approximately 70% of Americans aged 50-79 undergo at least annually.^13,14 If everyone received an annual MCED blood test in addition to current screening tests, we could potentially increase the CDR to 50%. Notably, this could include detection of some of the deadliest cancers, such as pancreatic, stomach, and lung cancers, which all currently have 5-year survival rates of less than 50%.^1,7

Why is MCED such a groundbreaking idea? Because it is simply not feasible to spend billions of dollars over decades to develop and test new screening approaches for each individual cancer. An MCED test could increase CDRs, and yield low false-positive rates which could translate into tremendous benefits for the population. Used alone, MCED tests may still miss some cancers, but some detection is better than no detection.

From an employer’s perspective, stage of disease at diagnosis is an important predictor of clinical outcome and treatment cost, because treatment of advanced-stage cancer is often more intensive than earlier-stage cancer. MCED tests have the potential to reduce per-case resource utilization for cancer management by shifting cancer treatment to earlier stages when fewer resources are needed and cost of treatment is lower. Indeed, 2 to 4 stage I patients could potentially be treated for the same cost as treating 1 stage IV patient (GRAIL, Inc; unpublished data on file). Additionally, early detection of cancers leads to fewer disability claims and less frequent early departure from the workforce.¹⁵

In conclusion, it is safe to say that the burden of cancer, both clinically and economically, is immense. While we are making advances in developing novel therapeutics, cancer screening or early detection technologies have not innovated at the same pace thus far, leading to unacceptable cancer mortality numbers. The development of MCED tests could help alleviate this crisis, because these tests could lead to early detection when patient outcomes are more favorable, and they could substantially increase the CDR when compared to the current strategy of single-cancer screening tests. The forthcoming commercial availability of MCED tests could potentially translate to an important value proposition for patients, employers, and payers due to their potential to improve patient-centered outcomes, and the use of MCED tests could lower direct and indirect costs associated with each case diagnosed.

About the Authors

Joshua J. Ofman, MD, MSHS is the chief medical officer and head of external affairs at GRAIL Inc. Azra Raza, MD is the Chan Soon-Shiong professor of medicine and director of the Myelodisplastic Syndrome (MDS) Center at Columbia University in New York, and author of “The First Cell: And the Human Costs of Pursuing Cancer to the Last.” A. Mark Fendrick, MD, is director of the University of Michigan Center for Value-Based Insurance Design.

References

1. Cancer Facts & Figures. American Cancer Society; 2020. Accessed November 17, 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/ 2020/cancer-facts-and-figures-2020.pdf

2. 2019 Sun Life Stop-Loss Research Report: High-cost Claims and Injectable Drug Trends Analysis. Sun Life Assurance Company of Canada; 2019. Accessed November 17, 2020. https://www.poweredbyc2.com/wp-content/uploads/2019/06/Sun-Life-2019-High-cost-claims-and-injectabledrug-trends-report-1.pdf

3. Medical Expenditure Panel Survey. Agency for Healthcare Research and Quality; 2018. Accessed November 17, 2020. https://meps.ahrq.gov/mepsweb/

4. Mariotto AB, Enewold L, Zhao J, Zeruto CA, Yabroff KR. Medical Care Costs Associated with Cancer Survivorship in the United States. Cancer Epidemiol Biomarkers Prev. 2020;29(7):1304-1312. doi:10.1158/1055-9965.EPI-19-1534

5. Nobel J, Sasser E, Weiss J, Pickering L. Cancer and the Workplace: The Employer Perspective. Northeast Business Group on Health; 2015. Accessed November 16, 2020. https://nebgh.org/wp-content/uploads/2015/10/CancerWorkplace_FINAL.pdf

6. Noone AM, Howlader N, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2015. National Cancer Institute. April 2018. Updated September 10, 2018. Accessed November 17, 2020. http://seer.cancer.gov/csr/1975_2015/

7. Calculated from Surveillance, Epidemiology, and End Results (SEER 18 Regs Research Data, Nov 2017 Submission. Includes persons aged 50-79. https://seer.cancer.gov/data-software/documentation/seerstat/nov2017/

8. Behavioral Risk Factor Surveillance System Prevalence & Trends Data. Centers for Disease Control and Prevention; 2015. Accessed November 17, 2020. https://www.cdc.gov/brfss/brfssprevalence/

9. Zahnd WE, Eberth JM. Lung Cancer Screening Utilization: A Behavioral Risk Factor Surveillance System Analysis. Am J Prev Med. 2019;57(2):250-255. doi:10.1016/j.amepre.2019.03.015

10. Liu MC, Oxnard GR, Klein EA, et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020;31(6):745-759. doi:10.1016/j.annonc.2020.02.011

11. Lennon AM, Buchanan A, Kinde I, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020;369(6499):eabb9601. doi:10.1126/science.abb9601

12. Chen X, Gole J, Gore A, et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat Commun. 2020;11(1):3475. doi:10.1038/s41467-020-17316-z

13. Projections of the population by sex and age for the United States: 2015 to 2060. US Census Bureau, Population Division; 2014. Updated May 9, 2017. Accessed November 17, 2020. https://www.census.gov/data/tables/2014/demo/popproj/2014-summary-tables.html

14. Rui P, Okeyode T. National Ambulatory Medical Care Survey: 2016 National Summary Tables. National Center for Health Statistics; 2016. Accessed November 17, 2020. https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2016_namcs_web_tables.pdf

15. Short PF, Vasey JJ, Tunceli K. Employment pathways in a large cohort of adult cancer survivors. Cancer. 2005;103(6):1292-1301. doi:10.1002/cncr.20912