Portal versus peripheral circulating tumor cells as prognostic biomarkers in patients with stage I-III pancreatic ductal adenocarcinoma

Background: Portal venous circulating tumor cells (CTCs) detection may better reflect vascular metastasis and predict micro-metastasis risk in PDAC than peripheral blood. We hypothesize that portal CTCs could better represent micro-metastasis and predict survival in PDAC patients. Methods: A single-center, prospective cohort study of patients with stage I-III PDAC was conducted. Portal venous blood was obtained via EUS-guided sampling, and peripheral blood was collected on the same day. CTCs were detected using EpCAM and mucin1 antibodies and reported as cells/8mL of blood. Results: Among 35 patients, portal and peripheral CTC detection rates were 94.3% and 82.9%, respectively. Advanced PDAC with loco-regional metastasis had higher portal CTCs than less aggressive disease (p<0.05), while peripheral CTCs showed no significant differences. During the 50-month follow-up, patients with portal CTCs≥8 had poorer survival (6.1 vs. 19.0 months, p=0.001) and patients with peripheral CTCs≥3 also had poorer survival (4.6 vs. 14.2 months, p=0.002). In multivariable analysis, both portal CTCs≥8 and peripheral CTCs≥3 showed significant adjusted associations with survival (aHRs 3.39 and 2.71; p=0.009 and 0.020). Conclusion: Higher CTC counts in both portal and peripheral systems were significantly associated with poorer survival in stage I-III PDAC; however, only portal CTCs reflected tumor aggression and loco-regional metastasis.