Transforming cancer screening: the potential of multi-cancer early detection (MCED) technologies

Abstract

Early cancer detection substantially improves the rate of patient survival; however, conventional screening methods are directed at single anatomical sites and focus primarily on a limited number of cancers, such as gastric, colorectal, lung, breast, and cervical cancer. Additionally, several cancers are inadequately screened, hindering early detection of 45.5% cases. In contrast, Multi-Cancer Early Detection (MCED) assays offer simultaneous screening of multiple cancers from a single liquid biopsy and identify molecular changes before symptom onset. These tests assess DNA mutations, abnormal DNA methylation patterns, fragmented DNA, and other tumor-derived biomarkers, indicating the presence of cancer and predicting its origin. Moreover, MCED assays concurrently detect multiple cancers without recommended screening protocols, potentially revolutionizing cancer screening and management. Large trials have reported promising results, achieving 50-95% sensitivity and 89-99% specificity for multiple cancer types. However, challenges, regarding improving accuracy, addressing ethical issues (e.g., psychosocial impact assessment), and integrating MCED into healthcare systems, must be addressed to achieve widespread adoption. Furthermore, prospective multi-institutional studies are crucial for demonstrating the clinical benefits in diverse populations. This review provides an overview of the principles, development status, and clinical significance of MCED tests, and discusses their potential and challenges.

Keywords: Cancer biomarkers; Cancer screening; Genomic sequencing; Liquid biopsy; Multi-cancer early detection; Oncology diagnostic technologies.

Fig. 1

Cancer type distribution and screening rates. a Distribution of cancer types in Japan. Proportion of cancer incidence by cancer type in Japan based on approximately 1 million total cancer cases per year. The dark gray segments represent the five types of cancer (colorectal, gastric, lung, breast, and cervical) currently targeted by the national screening programs, accounting for 54.5% of all incident cases. The remaining 45.5% cancer cases (shown in light gray) were not covered by existing screening programs. b Comparison of cancer screening rates across countries. Comparison of cancer screening rates among major countries. The graph shows the participation rates for breast cancer screening (dark gray), cervical cancer screening (light gray), and colorectal cancer screening (medium gray) in Japan, the United Kingdom, France, and Germany. In Japan, the screening rates for breast, cervical, and colorectal cancers are approximately 40%, which is lower than those in the other three countries

Fig. 2

Evaluation of MCED test performance. a In this model, samples were collected from a cohort of patients with and without cancer. The MCED test was performed on these samples to assess its sensitivity, specificity, and other performance characteristics by comparing the test results between the two cohorts. b In this model, the MCED test was administered to participants, and those who tested positive underwent diagnostic testing to confirm their cancer status. The positive predictive value and cancer detection rate of the MCED test was assessed based on the results of the diagnostic testing during the trial period. c In this model, participants were randomly assigned to either the MCED test group or a control group that does not receive the MCED test. Both groups were followed up for a defined period to determine their cancer status. The clinical utility of the MCED test, such as its ability to shift the cancer stage at diagnosis and reduce cancer-related mortality, were evaluated by comparing outcomes between the two groups