{
  "abstract": "Multi-Cancer Early Detection (MCED) blood tests, also known as liquid biopsies, are currently being studied in ongoing clinical trials in the US and UK. While most cancer screening focuses on mortality, the trials use detection of advanced cancer as the primary endpoint. Specifically, the largest ongoing trial – the UK National Health Service (NHS)-Galleri trial – has enrolled more than 140,000 people aged 50–77 with results expected in 2026 on a primary endpoint of absolute reduction in late-stage (stage 3 and 4) cancers. One MCED test has received the ‘Breakthrough’ designation by the FDA, which allows for surrogate markers as primary endpoints. These trials are intended to support regulatory approval and ultimately insurance coverage. MCEDs are also marketed directly to consumers and employers in the U.S. for cancer detection.In this setting, a critical analysis of MCEDs and their implications, particularly regarding overdiagnosis risks, mitigation strategies, and regulatory policy and coverage is direly needed.In a 60-minute interactive seminar, we will start with an introduction to MCEDs by Drs. Dhruva and Redberg, as they have discussed in their 2023 Editorial published in JAMA Internal Medicine (co-authored by Dr. Smith-Bindman): https://pubmed.ncbi.nlm.nih.gov/37639263/The introduction will briefly present the rationale that MCED developers and advocates use (especially as related to detection of cancers for which there is no current screening modality). Drs. Dhruva and Redberg will then discuss the mechanisms driving risk of overdiagnosis and associated harms (overdiagnosis of indolent tumors that have not and would never cause symptoms or death, high rates of incidentalomas, testing cascades with PET-CT scans and other radiologic and invasive testing, and overtreatment). They will highlight the need for these screening trials to show benefit on all-cause mortality – and also that such trials are highly feasible. The seminar will discuss strategies to educate patients on the risks of premature dissemination of MCED testing and best approaches to regulatory policy and coverage.The central question for full group discussion, facilitated by Drs. Dhruva and Redberg as well as Woloshin and Kramer, will be: ‘What is the most significant challenge in communicating the specific risk of overdiagnosis related to MCED tests to patients, AND what is one critical action (clinical, policy, or research) that we can take to mitigate widespread overdiagnosis from these tests?’Potential avenues for mitigating this risk include:-Regulation: Advocating that RCTs with all-cause mortality must be required for regulatory approval and payer coverage, including addressing the false perception created by the ‘Breakthrough’ designation by the FDA.-Marketing: Limiting marketing in the absence of evidence of clinical benefit. Requiring more transparent and accurate marketing, highlighting misleading claims about MCEDs.-Communicating the risks of overdiagnosis amidst hype: e.g., using absolute risks, discussing uncertainty, and lack of mortality benefit.-Engaging clinicians to counsel patients about the risks of direct-to-consumer MCEDs.Ultimately this seminar will provide attendees with a deep understanding of how MCED tests uniquely increase overdiagnosis, and identifying mitigation strategies to prioritize rigorous evidence of net benefit in all-cause mortality while preventing unnecessary harm to patients.",
  "authors": [
    {
      "affiliations": [
        "UCSF, San Francisco, USA"
      ],
      "name": "Sanket Dhruva"
    },
    {
      "affiliations": [
        "UCSF, San Francisco, USA"
      ],
      "name": "Rita Redberg"
    }
  ],
  "title": "092 Preventing an epidemic of overdiagnosis with multi-cancer early detection tests for cancer screening",
  "uid": "85b72001-4bb9-5bcc-b86f-a188628a330b"
}