Cancer screening with multicancer detection tests: A translational science review

Abstract

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

Keywords: clinical trials; health disparities; hematology/medical oncology; pathology and laboratory medicine; screening and early detection.

FIGURE 1

Translation of an MCD assay from the laboratory to clinical practice: stage of development and examples of MCD tests at each stage. This assessment of stage of development is limited to publicly available information. Some studies may not be represented here. The preclinical exploratory phase is an active area of assay development, and we did not attempt to comprehensively represent this work here. Information last reviewed April 24, 2023. MCD indicates multicancer detection.

FIGURE 2

Possible outcomes from an MCD screening test. Description of possible outcomes from positive and negative MCD signals and diagnostic workup, including benefits (e.g., reduced mortality and morbidity) and harms. Decreased adherence to recommended screening and decreased healthy behaviors may be mediated through false reassurance for true-negative and false-negative MCD screening results in addition to false-negative diagnostic workups. Delayed treatment may result from false-negative MCD screening results. Patient follow-up is unclear for false-negative diagnostic workups. MCD indicates multicancer detection.