Establishing a decision-making threshold for PIVKA II in the diagnosis of pancreatic ductal Adenocarcinoma (PDAC): a single centre experience

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide. Due to the crucial importance of an earlier identification of PDAC, there is substantial ongoing effort to identify serological biomarkers that would facilitate the timely detection of this malignancy. Protein Induced by Vitamin K Absence II (PIVKA II), a modified prothrombin, has been recently suggested as promising diagnostic marker for PDAC detection: however, in literature no diagnostic cut-off have been proposed for PDAC diagnosis yet. Aim of this research was to identify PIVKA II decisional threshold in PDAC patients, comparing their serum values to those found in HCC patients since the clinical-diagnostic validity of PIVKA II in HCC has already been widely demonstrated. Methods: Serum PIVKA II levels were measured in 91 PDAC patients, 92 HCC patients, and 59 healthy donors using an automated chemiluminescent enzyme immunoassay. Statistical analysis, including Receiver Operating Characteristic (ROC) curves, was used to establish sensitivity, specificity, and the optimal diagnostic threshold. Results: The optimal PIVKA II cut-off for PDAC diagnosis was 69 ng/mL, yielding a sensitivity of 80% and specificity of 94%. Comparable performance was observed in HCC patients (sensitivity 87%, specificity 94%). PIVKA II levels distinguished PDAC patients from healthy controls and demonstrated diagnostic potential similar to HCC, suggesting a shared biomarker profile. Conclusion: This study establishes a novel cut-off for PIVKA II in PDAC, supporting its utility as a biomarker. Further research is needed to validate these findings across diverse populations.