Promises and challenges of early detection of several cancers… : Oncology Times
Early multi-cancer screening tests using a blood sample (liquid biopsy) make it possible to detect cancer signals very early, giving hope for earlier, more effective or even curative treatments. Currently, standard screening tests only exist for a limited number of cancers, and each is designed to detect only one type of cancer.
To consider a new path for earlier detection of cancers through screening, the Friends of Cancer Research (FOCR) have published a new white paper, Early Detection Tests for Multiple Cancers: Considerations for Using Real Data. The organization also hosted an online briefing to introduce the concepts of the publication, which grew out of discussions between government officials, industry test developers, academic researchers and community groups. patient advocacy.
Currently, there is legislation in Congress that would cover multiple cancer early detection (MCED) tests for Medicare patients if approved by the FDA. The Medicare Multi-Cancer Early Detection Screening Coverage Act is a bill that would authorize the Centers for Medicare & Medicaid Services to evaluate and cover these multi-cancer screening blood tests, which are used to screen for cancer in many types of cancer.
A policy article published in the March 2022 issue of the journal Health Affairs also emphasizes the use of systematically collected real-world data to assess the clinical validity, utility, and economic value of multicancer screening tests (2022; https://doi.org/10.1377/hlthaff.2021.01316).
“Everything about cancer moves so much faster,” Norman E. “Ned” Sharpless, MD, director of the National Cancer Institute (NCI), said during the briefing. He pointed out that the last 10 years have produced remarkable progress in the fight against cancer thanks to new technologies. Due to the rapid pace of discovery, he noted that “while we may never eradicate cancer for all,” he believes President Biden’s recent efforts to revive and energize the Cancer Moonshot will achieve his goal of reducing cancer mortality. cancer in the United States by at least 50 percent. over the next 25 years.
But, Sharpless noted, “The truth is that we still find many cancers too late.” One way to improve that outlook is to supplement the single-organ screening tests currently used with MCED screening tests, he said.
The NCI Director praised FOCR for sponsoring the white paper and online briefing, saying it is essential to accurately assess the benefits and risks of MCEDs before they are used in clinical practice . Although they hold great promise for earlier detection, Sharpless noted that MCEDs could also lead to overdiagnosis and false positives.
If used correctly and carefully, MCEDs could very well revolutionize cancer detection, said Ernest Hawk, MD, MPH, vice president and division chief for cancer prevention and population sciences at the center. of Cancer MD Anderson from the University of Texas.
Data from randomized controlled trials (RCTs) are the gold standard for cancer survival, noted Ruth B. Etzioni, PhD, a member of the biostatistics program in the Public Health Sciences Division of the Center for Cancer Research. cancer Fred Hutchinson and affiliate professor at the university. from Washington. The white paper discusses the limitations of trial surrogates. “Remember that screening can only be beneficial as part of a continuum of care,” Etzioni said.
The new white paper noted that the NCI is “assessing the landscape of study designs and looking to potentially initiate a multi-arm, multi-stage pivotal RCT to evaluate multiple MCED screening tests in the coming years.” The use of real-world evidence gathered from real-world data (RWD) generated in the intended use population could “help supplement data generated in non-RWD clinical screening studies and can be used to inform regulatory decisions,” the document reads.
Powering studies for each type of cancer in an RCT, especially rare cancers, is a logistical challenge because it requires large numbers of enrollments and one or more decades of follow-up to demonstrate a cancer-specific mortality benefit for individual cancer types. The FOCR white paper includes a figure on the types of study designs for screening tests that incorporate real-world data. For example, RWD could serve as an external control group, case-control study, or cohort study.
RWD resting outside the trial site offers “a chance to cast a wider net,” said Sam Roosz, MBA, CEO and co-founder of Crescendo Health. He said it was important to continue planning for data interoperability and “managing the data clutter” in the development of MCEDs.
For example, how do test developers determine if a negative MCED result is a true negative? The result of an MCED screening test should show a positive result in people with cancer (sensitivity) while providing a negative result in people who do not have cancer (specificity).
The key questions for MCED development posed by the white paper are:
- Performance characteristics: How well does the MCED screening test detect cancer? When does it detect cancer?
- Safety: What are the health burdens/harms of MCED screening tests, including the diagnostic confirmation process?
- Clinical outcomes and utility: What is the impact of an MCED screening test on cancer outcomes?
The FDA is currently reviewing the issues raised by MCEDs, said Wendy Rubinstein, MD, PhD, director of personalized medicine at the FDA’s Center for Devices and Radiological Health. She noted that in the short term, test developers will bring their MCEDs to the FDA for review and approval, and it is imperative to determine the benefits of the tests before they are rolled out for use in the general public.
“If we don’t plan now, we won’t even have the answers in 5 or 10 years,” Rubinstein said. She underscored the need to harmonize data collection standards for MCEDs as their development progresses.
She also noted that assessing the potential harms of MCEDs is just as important as assessing their benefits. For example, she said a positive MCED screening test result could lead to an invasive diagnostic workup, resulting in an adverse patient outcome, such as pancreatitis.
“We need to think about MCEDs in a more nuanced way,” said Seema Singh Bhan, JD, vice president of public policy and external affairs at Exact Sciences Corp. “There is no clear path for MCEDs.”
She noted that today more than 70% of cancers are diagnosed at advanced stages and single-organ screening tests are the norm, stressing that research into future MCEDs will be more useful when they complement the current screening tests. “This is a future where everyone can get an early diagnosis,” Bhan said.
MCEDs must have both clinical validity and clinical utility. And they must have something more: patient acceptance. From a patient perspective, MCEDs could be used in the future to identify at-risk individuals who could benefit from lifestyle and behavior changes that reduce their cancer risk, said Jody Hoyos, MHA, president and Chief Operating Officer of Prevent Cancer Foundation. But she noted that how patients accept MCEDs will be critical to the extent of their use in clinical practice.
OCRF President and Founder Ellen Sigal, PhD, said she knows MCEDs are a complex topic, and the new white paper is just the beginning of the discussion about their potential value in early diagnosis of cancer. cancer.
Interviews with professionals contributing to the white paper highlighted the need for alignment on terminology used in the development, validation and evaluation of MCED screening tests. Another area that needs attention, highlighted in the white paper, “is the use of machine learning and artificial intelligence by many MCED screening tests to determine cancer status.”
The article highlights that real-world evidence “can enable real-world learning and evaluation of these technologies as they enter clinical practice, helping to achieve the goal of a health care system. health learner”. In this regard, real-world evidence can play a role in the “periodic (post-marketing) re-evaluation of MCED screening tests using machine learning to assess the actual performance of initial and future versions of these tests”, the book white indicated.
Peggy Eastman is a contributing writer.