Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population

Abstract Background: Globally, cancer results in 10.08 million deaths per year. A single blood-based screening tool that detects multiple cancer types could greatly reduce cancer burden. We aim to systematically review and statistically examine both the accuracy and applicability of blood-based MCED tests to strategize their utilization in improving cancer detection. Methods: Original articles were searched from Pubmed, Cochrane, and Embase for blood-based screening tests analyzing multiple cancer types and asymptomatic human subjects. We excluded studies with small sample size (n<30), hypothesis-generating tests, and non-blood based tests. For cell-free DNA (cfDNA) based assays, measurements of diagnostic accuracy were pooled for meta-analysis. Findings: Of 1,074 records screened, 10 case-control and 6 cohort studies were analyzed, most of which utilized cfDNA-based diagnostic tests. Ten cfDNA studies selected for meta-analysis had a joint sensitivity of 0.66 (95%CI 0.54-0.75) and specificity of 0.98 (0.94-0.99) with an area under the curve of 0.883. For cohort studies, the joint positive and negative predictive values were 0.96 (0.29-1.00) and 0.81 (0.37-0.97) respectively. Sensitivity was higher for advanced staged cancers (III/IV 0.84 (0.84-0.86)) with breast cancer having the lowest sensitivity (0.42 (0.31-0.55)). Sensitivity and specificity were not affected by study type, gender, or assay type. Lastly, accuracy of tumor origin prediction was 0.792 (0.64-0.91) without significant differences across cancer types. Interpretation: Given high sensitivities and specificities, MCED tests show promise as additional screening tools. Although there exist multiple barriers to their application in clinic, MCED tests may improve patient outcomes for cancers with no conventional screening tools. Future prospective studies with large and diverse populations are warranted. Summarization of meta-analysis results on cfDNA based multi cancer early detection tests Sensitivity Specificity DOR PPV NPV No. of study included 10 10 10 4 4 Events/Total 5778/10033 14797/15020 Experimental group: 5778/6001 901/1373 10148/11216 Control group: 4202/19052 Proportion (95% CI) 0.652 [0.537; 0.751] 0.978 [0.936; 0.992] 69.290 [25.208; 190.457] 0.961 [0.293; 0.999] 0.812 [0.365; 0.970] Heterogeneity (p value) 98% (<0.01) 97% (<0.01) 96% (<0.01) 99% (<0.01) 100% (<0.01) Abbreviations: CI = confidence interval; DOR = diagnostic odds ratio; PPV = positive predictive value; NPV = negative predictive value Citation Format: Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie A. Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Young Kwang Chae. Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 783.