Multi-cancer early detection tests for general population screening: a systematic literature review

Project overview 

The aim of this project was to conduct a systematic review to assess the accuracy and clinical effectiveness, acceptability and feasibility of blood-based MCED tests for population-based screening.

Status: completed

Contact: sofia.dias@york.ac.uk

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What is the problem?

General population cancer screening in the UK is limited to selected cancers (cervical, breast, bowel and, for some high-risk individuals, lung). Most other cancers are detected after presentation of symptoms, when the disease tends to be at a more advanced stage and treatment options may be more limited. Blood-based multi-cancer early detection (MCED) tests aim to detect potential cancer signals (such as circulating cell-free deoxyribonucleic acid) from multiple cancers in the blood. 

The use of a MCED test as a screening tool in a healthy, asymptomatic population requires a high specificity and a reasonable sensitivity to detect early-stage disease so that the benefits of earlier diagnosis and treatment can be realised. A MCED test embedded within a national population-based screening programme, in addition to existing cancer screening programmes, may increase the number of cancers diagnosed at an earlier stage. However, identification of cancers with no effective treatments, even at an early stage, may offer no improvement in mortality or health-related quality of life (HRQoL). In addition, screening of healthy people for a wide range of cancers, and the expected lengthy time to diagnostic confirmation, may create anxiety and lead to unnecessary follow-up tests when false-positive test results occur.

Cancer screening is only available for some cancers. New tests that look for signs of cancer in blood (blood-based multi-cancer early detection tests) are being developed; they aim to detect multiple different cancers at an early stage, when they are potentially more treatable.

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What did we do?

Taking account of stakeholder feedback, we reviewed all studies assessing the effectiveness of blood-based multi-cancer early detection tests for cancer screening. We thoroughly searched for relevant studies and found over 8000 records. We included 30 completed studies and 6 ongoing studies of 13 different tests. 

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What did we find?

None of the studies were of good quality, mainly because they did not properly check whether the test result might have been incorrect and whether participants with a negative test result actually had cancer. Most studies included participants who are different from the general United Kingdom population that would likely be invited for this type of cancer screening test. None of the studies reported meaningful results for patient-relevant outcomes, such as death, potential harms, quality of life and acceptability. We found 14 completed studies assessing 6 tests that are currently available: Galleri® (GRAIL, Menlo Park, CA, USA), CancerSEEK (Exact Sciences, Madison, WI, USA), SPOT-MAS™ (Gene Solutions, Ho Chi Minh City, Vietnam), Trucheck™ (Datar Cancer Genetics, Bayreuth, Germany), Cancer Differentiation Analysis (AnPac Bio, Shanghai, China) and AICS® (AminoIndex Cancer Screening; Ajinomoto, Tokyo, Japan). All of the tests were quite good at ruling out cancer, but their accuracy for finding cancer varied a lot, mostly because of differences in the study methods and characteristics of the included participants. The tests were better at finding more advanced cancers, which are potentially less curable than early cancers, so more research is needed to know whether tests would actually save lives. Better-designed studies including participants similar to those who might get the test in the real world, and which report on patient-relevant outcomes and properly consider patient experience and impact on services, are needed. Several new studies are planned or underway.