Multicancer detection (MCD) assay developers could have something to celebrate soon as a group of U.S. lawmakers continues their push for Medicare coverage of genomic sequencing and other emerging clinical laboratory testing technologies for early cancer detection screening.
HR 2407, also known as the Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act, is scheduled to go to House Ways and Means Committee markup June 27. The purpose of the act is to create a covered benefit for multicancer early detection screening tests that have been approved by the U.S. Food and Drug Administration (FDA).
Sponsored by Texas Rep. Jodey Arrington (R, TX-19) and named after Alabama Rep. Terri Sewell's (D, AL-07) late mother, HR 2407 aims to "open the door to a new era of detecting and treating cancer," stated an appeal from Sewell's office in 2023 when the bill was first introduced with bipartisan support and a Senate companion bill.
As a new tool for cancer screening, multicancer detection tests make a prediction about the presence of cancer, not a diagnosis, according to the National Cancer Institute (NCI). Also referred to as MCD and multicancer early detection (MCED) assays or liquid biopsy tests, these clinical laboratory tests measure biological substances that cancer cells may shed in blood and other body fluids, such as circulating tumor cells, tumor DNA, and other analytes that may suggest the presence of cancer.
In May, NCI noted multicancer detection tests currently in development included those that target the following:
- Changes in DNA and/or RNA sequences;
- Patterns of DNA methylation (a chemical change to DNA which changes how the gene product is expressed);
- Patterns of DNA fragmentation (how the DNA is broken into smaller pieces);
- Levels of protein biomarkers;
- Antibodies that a person’s body may develop against components of growing cancer cells.
The NCI has called MCD/MCED tests "rapidly evolving emerging technology," where no comprehensive centralized listing of tests is available to the public. Although these tests are available as laboratory developed tests (LDTs) and a few have received breakthrough device designation from the FDA, no MCD tests have been authorized by the FDA, NCI pointed out.
"There are many unanswered questions about the use of MCD tests to screen for multiple cancers," stated NCI in an MCD test Q&A. "Despite these unknowns, healthcare professionals and patients are faced with a marketing tsunami of MCD tests in various stages of development."
While HR 2407 stands a chance to advance and create a Medicare benefit category, more work lies ahead for MCD assay developers with clinical trial developments anticipated in 2025. This is when the Cancer Screening Research Network (CSRN) will start enrolling up to 24,000 healthy people from ages 45 to 70 in the Vanguard Study on Multi-Cancer Detection.
NCI is also funding the collection of blood samples to establish a large bank of case-control samples to use in evaluating MCD tests in future studies.
Vanguard was established to assess the feasibility and finalize the design and logistics for the larger study of multicancer early detection screening tests. Vanguard will lay the groundwork for large-scale clinical trials and other studies to assess multiple different technologies for cancer screening.
Multicancer detection test investigators will come from a variety of disciplines that are actively engaged in cancer screening, according to CSRN. With Fred Hutchinson Cancer Center in Seattle designated as the statistics and data management center, additional Accrual, Enrollment, and Screening Site "ACCESS" hubs are funded for MCD research, which include the following:
- Henry Ford Health and Michigan State University Health Sciences in Detroit
- Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente School of Medicine
- OU Health Stephenson Cancer Center at the University of Oklahoma Health Sciences in Oklahoma City
- University of Colorado Cancer Center in Aurora
- University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill
- Virginia Commonwealth University in Richmond, Inova, and Sentara Health
- Washington University School of Medicine in St. Louis
- The Department of Defense Uniformed Services University and the Department of Veterans Affairs
Dr. Marie Wood, medical director of the Cancer Clinical Trials Office and one of the University of Colorado Cancer Center investigators on the Vanguard Study, in a CU Cancer Center announcement in April said 50% of all cancers occur in cancers for which there currently [are] screening tests; however, a substantial portion of cancer deaths occur from cancers for which there is no standard screening.
“Currently, we have standard of care screening for five cancers — breast, cervical, colorectal, lung, and prostate — but these screenings are all done using different modalities, done at different intervals, starting at different ages, with differing amounts of invasiveness. They’re also associated with a high false positive rate and low predictive value," Wood said.
“These multicancer detection tests are looking at biomarkers, commonly DNA in the blood, and many companies are proposing to use these as a screening test. A simple blood test that screens for multiple types of cancer — including cancers with no current standard-of-care screening — could improve early detection of cancers, but only if they work properly and don’t create more problems than they solve," Wood continued.
“The problem with multicancer detection tests is that they just give you the probability that you might, for example, have pancreatic cancer, which is a cancer for which there is no screening,” added Dr. Linda Cook, associate director of population sciences for the CU Cancer Center.
“So you arrive to your specialist doctor and say, ‘I have an X percent chance of having this cancer,’ and then they have to do massive workups on you to figure out what the cancer is and if you actually have it," Cook continued. "It’s not as much about the cost and the investment in the screening tool itself — it's the downstream consequences.”
Data collected through Vanguard can be used to develop evidence-based guidelines for cancer screening, Dr. Lori Minasian, deputy director of the Division of Cancer Prevention at NCI, said in an NCI statement in February, when CSRN launched for the purpose of evaluating MCD tests, among others.
“There are many cancers we still cannot reliably detect until it is so late that they become extremely difficult to treat,” NCI Director Dr. W. Kimryn Rathmell said at the time. “Emerging technologies such as multicancer detection tests could transform cancer screening and help to extend the lives of many more people. We need to be sure that these technologies work and understand how to use them so they benefit everyone.”
Prior to the Ways and Means Committee's consideration of HR 2407, the bill specified that multicancer early detection screening tests means tests approved or cleared by the FDA, such as genomic-sequencing blood or blood product tests that include the analysis of cell-free nucleic acids, and such other equivalent tests (which are based on blood, blood products, urine, or other sample of biological material) as determined appropriate.
Regardless of whether HR 2407 advances, the road ahead for MCD tests will likely still be slow. CU Cancer Center's Cook said clinical trials will be assessing survival rates over a number of years.
