Clinical significance of serum CA125 kinetics as an early predictor of tumor progression in pancreatic cancer patients.

768 Background: Serum carbohydrate antigen 125 (CA125) is a well-established marker for the diagnosis of ovarian cancer. However, its significance in pancreatic cancer (PC) remains unclear. This study aimed to clarify the association between serum CA125 levels and clinical characteristics, and to evaluate the clinical relevance of its kinetics during chemotherapy. Methods: CA125 expression in PC tissues was examined immunohistochemically. A retrospective analysis was conducted in 152 patients with PC who received first-line chemotherapy (gemcitabine plus nab-paclitaxel or modified FOLFIRINOX) between January 2014 and July 2024 at three institutions. Patient characteristics and treatment outcomes were compared between groups with elevated and normal CA125. CA125 kinetics were assessed using baseline and initial follow-up values, and their correlation with clinical response was analyzed. The association between CA125 kinetics and survival outcomes was also further evaluated using the optimal cut off value determined by receiver operating characteristic (ROC) curve analysis. Results: CA125 was expressed in primary lesions as well as in liver and peritoneal metastases. Baseline CA125 levels were significantly associated with the number of metastatic sites and severity of ascites (both p < 0.001). The median progression-free survival (PFS) and overall survival (OS) in the CA125-non-elevated group were significantly longer than those in the CA125-elevated group (PFS: 8.4 vs. 6.5 months; hazard ratio (HR), 0.58; p = 0.0057; OS: 17.9 vs. 12.6 months; HR, 0.57; p = 0.0051). Among 102 patients with both CA125 monitoring and measurable target lesions, CA125 kinetics correlated with tumor response (p < 0.001). ROC analysis identified an optimal threshold for CA125 increase predicting progressive disease as 0.173 %/day (sensitivity: 81.5%, specificity: 69.3%). Patients with increased CA125 kinetics had significantly shorter PFS and OS compared with those without (median PFS: 3.3 vs. 9.8 months, HR, 0.38; p < 0.0001; median OS: 10.1 vs. 17.3 months, HR, 0.48; p = 0.002). Conclusions: Serum CA125 may serve as a clinically useful biomarker in PC patients during chemotherapy. Notably, increase in CA125 kinetics can be an early predictor of tumor progression.