Early detection of cancer is crucial for improving patient outcomes. As cancer remains one of the leading causes of death worldwide, there is an increasing demand for effective screening methods that can identify multiple cancers simultaneously. However, the introduction of multi-cancer early detection (MCED) tests raises important questions about their efficacy, cost-effectiveness, and potential consequences for patients.
Cancer News
Addressing the Need for Early Detection
Table of Contents
The goal of MCED tests is to detect a variety of cancers at an earlier stage, ideally before symptoms manifest. A notable example is the GRAIL-Galleri test, which claims to identify over 50 types of cancer by analyzing circulating tumor DNA linked to aberrant methylation. This innovative approach could potentially expedite diagnosis and limit the need for invasive techniques like biopsies.
Key Issues with MCED Tests
- Sensitivity for Early-Stage Cancers: A screening test must have high sensitivity, especially for early-stage diseases, where intervention is more likely to lead to a cure. In its current form, the Galleri test has demonstrated an overall sensitivity of only 27.5% for early-stage cancers (stages I and II). This figure is based on performance in patients with symptomatic disease, which may overestimate the screening performance. When focusing on a set of 12 cancers that GRAIL identified as having high unmet needs, the sensitivity improved to 52.8%. However, for several of these cancers—such as pancreatic, oesophageal, biliary, and liver—the mortality gains from population screening may be limited, as they are typically diagnosed in individuals over the age of 70, and prognosis is poor regardless of stage.
- Implications of False Positives: The consequences of false-positive results can be significant. For a test that purports to detect more than 50 cancers, the imprecision in cancer signal origin analysis can lead to extensive follow-up tests. Patients often require additional imaging and diagnostic interventions, such as endoscopies, to confirm whether a positive screening result is accurate. These follow-up procedures can be invasive and carry their own risks, along with substantial healthcare costs. The psychological impact on patients receiving a false-positive result can also be considerable, causing anxiety and distress.
- Regulatory and Evaluation Standards: The UK National Screening Committee (NSC) has established a clear evaluation process for new screening proposals, which typically requires evidence of improvement in cancer-specific mortality from randomized trials. The current evaluation of the GRAIL-Galleri test raises concerns about the reliance on surrogate endpoints, such as stage-shift, rather than direct benefits in terms of mortality reduction. Past studies, such as those focused on ovarian cancer, have shown that while downstaging may occur at diagnosis, it does not necessarily translate into a reduction in cancer-specific mortality.
- Economic Considerations: The financial implications of implementing MCED tests are considerable. The Galleri test is priced at approximately $949 per test. If offered annually to the estimated 20.3 million citizens in the UK aged 50-77, the total annual cost could exceed $19.3 billion (approximately £15.8 billion). This raises questions about the test’s value for money and whether resources could be better allocated to established screening methods with proven effectiveness.
Final Thoughts
As interest in multi-cancer early detection tests grows, it is crucial to evaluate their effectiveness and economic impact carefully. The GRAIL-Galleri test exemplifies the challenges associated with implementing MCED tests in clinical practice. Ensuring that these tests demonstrate clear benefits in reducing cancer-specific mortality is essential for their acceptance. Patients concerned about cancer risk should consult healthcare providers about available screening options and consider the implications of new testing methods.
References
Turnbull, C., Wald, N., Sullivan, R., Pharoah, P., Houlston, R. S., Aggarwal, A., Hogarth, S., & McCartney, M. (2024). GRAIL-Galleri: Why the special treatment? The Lancet, 403(10425), 431-432. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02830-1/fulltext
University of Oxford. (2023). Multi-cancer blood test shows real promise in NHS trial. Retrieved on June 5, 2023, from https://www.ox.ac.uk/news/2023-06-02-multi-cancer-blood-test-shows-real-promise-nhs-trial
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