Multi-Cancer Early Detection Tests: An Overview of Emerging Technologies
Multi-cancer early detection (MCED) tests are being developed and marketed to detect early signs of numerous cancer types through a single blood test. Approximately 40 such tests are currently in development or on sale globally. However, a critical challenge remains: few of these tests have undergone randomized controlled trials (RCTs), which are considered the gold standard for clinical evidence. Furthermore, none have yet received regulatory approval from bodies like the FDA.
Galleri Test: First RCT Results Announced
The landscape of MCED testing recently saw a significant development with the release of details from the first randomized controlled trial involving the Galleri test, developed by Grail. Conducted in partnership with the UK National Health Service (NHS), this landmark trial aimed to assess whether the Galleri test could reduce advanced-stage cancer diagnoses when used alongside existing screening programs.
The results indicated that the test did not meet this primary objective.
The Galleri test's initial RCT, the first of its kind for an MCED test, found it did not reduce advanced-stage cancer diagnoses.
The Science Behind Liquid Biopsy
The scientific foundation of these tests, often referred to as 'liquid biopsy,' centers on utilizing markers of cancer detectable in bodily fluids, primarily blood. These markers include DNA fragments shed by cancer cells. This technology is not entirely new; it is already successfully employed to monitor cancer progression and guide treatment decisions.
However, detecting cancer at its earliest stages presents a significantly greater challenge. This is largely due to the extremely low concentration of tumor DNA in the blood, which can be as little as 0.006% of the free-floating DNA.
Liquid biopsy tests aim to detect cancer markers like DNA fragments in blood. While used for monitoring, early-stage detection is more challenging due to the very low concentration of tumor DNA.
Researchers like Bert Vogelstein have made substantial contributions to advancements in detecting circulating tumor DNA (ctDNA). Other innovative approaches being explored include assessing epigenetic changes, such as specific DNA methylation patterns, and analyzing the physical properties of tumor DNA fragments.
Expert Opinions and Current Limitations
The potential of MCED tests has sparked diverse reactions within the scientific and medical communities. Some researchers are optimistic, believing these tests could revolutionize cancer detection, particularly for cancers that currently lack effective screening tools. Conversely, others express significant caution, highlighting that these tests may fail to detect many early cancers.
Concerns include the potential for false positive diagnoses, which can lead to considerable patient anxiety and unnecessary invasive follow-up procedures. Questions also remain regarding whether the benefits of widespread MCED testing would truly outweigh the potential downsides, given the current data. Physician-researcher Eric Topol has critically observed that promoting these tests based on the available data is premature.
Expert opinions are divided: while some see MCED tests as revolutionary, others caution against potential false positives, patient anxiety, and unproven benefits given current data.
The Current Cancer Screening Landscape
Cancer remains a leading cause of death globally, underscoring the critical importance of early detection. Generally, cancers detected at an earlier stage are associated with less invasive treatments and significantly better survival rates. A major challenge is that most cancer deaths occur following late-stage diagnoses, further emphasizing the urgent need for earlier detection methods.
Existing preventive screening programs, such as mammography for breast cancer and colonoscopy for colorectal cancer, have proven effective. However, these programs have their own limitations, including varying uptake rates and a lack of screening options for many cancer types. In the U.S., preventive screening currently detects only a small fraction—14%—of all diagnosed cancers.
Evaluating MCED Tests: Key Metrics
Regulators and health systems worldwide evaluate MCED tests based on several critical performance metrics:
- Sensitivity: This measures the proportion of people with cancer who correctly receive a positive test result.
- Specificity: This indicates the proportion of people without cancer who are correctly identified as negative by the test.
- Positive Predictive Value (PPV): This is the proportion of positive test results that truly indicate the presence of cancer.
Systematic reviews suggest that MCED tests generally exhibit high specificity, ranging from 96–99.5%, but show more variable sensitivity, typically between 30–80%. Clinical trials have yielded mixed results; for example, a study involving the CancerSEEK test in women aged 65–75 detected only 26 out of 96 diagnosed cancers, while accurately ruling out cancer in 98.9% of those without the disease.
While MCED tests show high specificity (96-99.5%), their sensitivity is more variable (30-80%), indicating a challenge in consistently detecting early cancers.