Real-world performance of a multimodal cell-free DNA multi-cancer early detection test in Asian populations.

14 Background: Multi-cancer early detection (MCED) addresses a critical unmet need by enabling simultaneous screening for multiple malignancies, particularly those lacking standard-of-care (SOC) options. SPOT-MAS is a liquid biopsy assay integrating methylomic, fragmentomic, and genomic signatures of cell-free DNA to detect signals across 10 cancer types. Building on its validation in the K-DETEK trial (NCT05227261), this study evaluates the clinical performance and feasibility of SPOT-MAS in a large-scale, real-world cohort across six Asian countries. Methods: Plasma cfDNA samples were analyzed from 84,145 individuals undergoing SPOT-MAS testing. Of these, 22,597 asymptomatic participants who completed a mandatory 12-month follow-up were included in the analysis. Participants with positive ctDNA signals underwent standardized post-test consultation and diagnostic workup, including imaging and/or histopathology, according to a predefined protocol to establish clinical status. Results: SPOT-MAS identified 94 positive cases (0.42%). Diagnostic workup confirmed 64 malignancies or precancerous lesions, including 20 cases (31.2%) diagnosed with cancers lacking SOC screening options, yielding a PPV of 68.1%. The assay demonstrated a Sensitivity of 79.0%, Specificity of 99.9%, NPV of 99.9% and Tissue-of-Origin accuracy of 80.0%. These performance metrics are consistent with the results of the K-DETEK trial. Conclusions: To the best of our knowledge, this study provides the first large-scale real-world evidence from Asia supporting the robustness and clinical utility of SPOT-MAS as a complementary screening strategy, particularly in LMICs lacking accessible national screening programs. Diagnostic performance comparison of the SPOT-MAS multi-cancer early detection test between the prospective K-DETEK trial and the expanded real-world data cohort. Test performance K-DETEK Real-World Data N = 9,024 % (95%CI) N = 22,597 % (95%CI) ctDNA signal detected 43 0.48 94 0.42 True positive 25 0.28 64 0.28 - Precancerous lesions 8 0.09 32 0.14 - Cancerous lesions 17 0.19 32 0.14 False positive 18 0.20 30 0.13 ctDNA signal not detected 8,981 99.52 22,503 99.58 True negative 8,974 99.45 22,486 99.51 False negative 7 0.08 17 0.08 - Precancerous lesions 0 0.00 7 0.03 - Cancerous lesions 7 0.08 10 0.04 Sensitivity 78.12 (61.24–88.98) 79.01 (68.93–86.46) Specificity 99.80 (99.68–99.87) 99.87 (99.81–99.91) Positive predictive value 58.14 (43.33–71.62)