Impact of anti-PD1 immunotherapy and circulating tumor cells on progression-free survival in surgical pancreatic adenocarcinoma: a retrospective cohort study

Expert Rev Clin Immunol. 2025 Jan 2. doi: 10.1080/1744666X.2024.2448989. Online ahead of print.

Abstract

Introduction: The clinical benefits of combining immunotherapy with chemotherapy and surgical resection in pancreatic adenocarcinoma remain unclear. The expression and clinical significance of HIF1A in circulating tumor cells (CTCs) in pancreatic adenocarcinoma remains limited.

Methods: This retrospective cohort study compared survival outcomes in pancreatic adenocarcinoma patients treated with two regimens: surgery+chemotherapy (nab-paclitaxel plus gemcitabine)+anti-PD1 (Tislelizumab) (S+AG+anti-PD1), and surgery+chemotherapy (S+AG). The study also evaluated CTCs and HIF1A-positive CTCs as potential prognostic biomarkers. Fifty-two patients were included in the two treatment groups.

Results: The S+AG+anti-PD1 group (n = 37) showed significantly better progression-free survival (PFS) compared to S+AG (n = 15) in multivariate analysis (HR: 0.426, 95% CI: 0.185-0.983, p = 0.045). Overall survival (OS) differences were not statistically significant between groups. Lower CTC counts (≤1) were associated with longer PFS in surgical patients. This association was confirmed in multivariate analysis, after adjustment for AJCC stages (HR: 0.318, 95% CI: 0.104-0.974, p = 0.045). HIF1A-positive CTCs showed similar trends and prognostic significance to total CTC counts. Advanced AJCC stages remained the strongest independent predictor of worse PFS and OS.

Conclusion: This study suggests that combining surgery, chemotherapy, and immunotherapy may improve PFS in resectable pancreatic adenocarcinoma. While CTCs and HIF1A-positive CTCs may have prognostic value, AJCC staging remains the most reliable indicator.

Keywords: Circulating tumor cells; HIF1A; immunotherapy; pancreatic adenocarcinoma; prognosis.