Abstract A081: Prospective Evaluation of a Regulatory-Approved ApoA2-Isoform In Vitro Diagnostic Assay for Pancreatic Cancer Risk Stratification Toward Interception in a Community-Based Screening Cohort
Kazufumi Honda, Masaki Kuwatani, Shiroh Tanoue, Hiroshi Fujita, Hiroki Taguchi, Kaoru Oketani, Mototsugu Kato, Keiko Takeuchi, Hiroshi Konishi, Hirohito Tsubouchi, Naoya Sakamoto, Akio Ido, Ayumi Kashiro, Kengo NagashimaAbstract
Background:
Early detection and interception are essential for improving outcomes of pancreatic cancer (PC). Blood-based biomarkers capable of identifying individuals at increased risk before clinical diagnosis may enable targeted imaging surveillance and interception strategies. Since 2017, we have conducted a prospective pancreatic cancer screening program among community-dwelling individuals aged 50 years or older using a research-use-only (RUO) ApoA2-isoform assay. However, the original RUO assay differed from the subsequently approved in vitro diagnostic (IVD) assay in assay design and quality-control procedures. Therefore, all archived plasma samples were remeasured using the PMDA-approved ApoA2-i IVD assay to evaluate its ability to identify individuals at elevated future risk of pancreatic cancer and support risk-stratified interception approaches.
Methods:
Archived plasma samples from a prospective screening cohort were remeasured de novo using the PMDA-approved ApoA2-i IVD assay. Results from the original RUO assay were not used. A total of 13,276 individuals aged 50 years or older were followed through regional cancer registries for up to four years. Participants were classified using the predefined clinical cut-off value of 60 μg/mL.
Results:
During follow-up, 20 pancreatic cancers were diagnosed. ApoA2-i positivity was observed in 452 individuals (3.4%), among whom six pancreatic cancers were identified (PPV 1.33%). Compared with ApoA2-i–negative individuals, participants with ApoA2-i levels below the clinical cut-off exhibited substantially increased risk of pancreatic cancer diagnosis. Risk ratios were 56.8 (95% CI, 14.5–222.6) for cancers diagnosed within 1 year, 21.3 (95% CI, 7.6–59.6) within 2 years, 15.5 (95% CI, 5.9–40.9) within 3 years, and 12.2 (95% CI, 4.7–31.5) during overall follow-up. Sensitivity was 66.7% for cancers diagnosed within 1 year and 30.0% during overall follow-up. Individuals with ApoA2-i levels below 60 μg/mL demonstrated significantly higher cumulative pancreatic cancer diagnosis rates than those above the cut-off (log-rank P < 0.001). Importantly, 50% of pancreatic cancers diagnosed during follow-up were detected at potentially curable R0-resectable stages.
Conclusions:
This study represents the first prospective evaluation of a regulatory-approved ApoA2-i IVD assay in a community-based screening cohort. ApoA2-i identified a small subgroup comprising only 3.4% of the screened population but exhibiting markedly elevated risk of future pancreatic cancer diagnosis. These findings support the clinical utility of ApoA2-i as a practical blood-based tool for pancreatic cancer risk stratification and for identifying individuals who may benefit from risk-adapted imaging surveillance and interception strategies. Integration of ApoA2-i–based risk stratification with targeted imaging may provide a scalable approach for pancreatic cancer interception in the general population.
Citation Format:
Kazufumi Honda, Masaki Kuwatani, Shiroh Tanoue, Hiroshi Fujita, Hiroki Taguchi, Kaoru Oketani, Mototsugu Kato, Keiko Takeuchi, Hiroshi Konishi, Hirohito Tsubouchi, Naoya Sakamoto, Akio Ido, Ayumi Kashiro, Kengo Nagashima. Prospective Evaluation of a Regulatory-Approved ApoA2-Isoform In Vitro Diagnostic Assay for Pancreatic Cancer Risk Stratification Toward Interception in a Community-Based Screening Cohort [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A081.