How about the impact of tumor regression grade on pancreatic adenocarcinoma survival?

779 Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, with a 5-year survival rate of approximately 13%. Although neoadjuvant chemotherapy +/- radiotherapy has improved resectability and survival most patients continue to succumb to the disease. As a result, identifying biomarkers is essential to optimize patient selection and therapeutic strategies. Methods: We retrospectively collected data from PDAC patients who underwent neoadjuvant therapy followed by an operation at Cedars Sinai Medical Center between September 2014 and September 2024. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Correlations between postoperative pathologic features (histologic subtype, grading, tumor regression grade (TRG), perineural invasion, perivascular invasion, staging, margin status) and survival outcomes (RFS and OS) were assessed using the log-rank test. Multivariable analysis was performed using the Cox proportional hazards model. Results: Of the 351 patients resected, 89 had preoperative biopsies and post neoadjuvant surgical specimens. At a median follow-up of 31.3 months (95% CI, 23.6-NR), the median RFS and OS were 12.0 (95% CI, 8.6-14.2) and 28.0 months (95% CI, 18.0-45.9), respectively. TRG (p=0.002 and p=0.001), perivascular invasion (p=0.046 and p=0.050), and tumor size (p=0.019 and p=0.019) were correlated with both RFS and OS. In multivariable analysis, TRG remained the only independent predictor for both RFS (p=0.050) and OS (p=0.023). Specifically, patients with complete or major pathologic responses (TRG 0-1) had improved survival outcomes as compared to those with minimal response (TRG 2-3). Additionally, patients with lower TRG (0-1) had a lower risk of liver recurrence than those with higher TRG (2-3) (OR 0.247, 95% CI, 0.090-0.677, p=0.004). In contrast, no significant correlation between TRG and other recurrence sites (local and distant) as well as any differences in survival outcomes based on chemotherapy regimen (FOLFIRINOX vs. gemcitabine-abraxane) or the use of radiotherapy were identified. Conclusions: Our study demonstrates that TRG is an independent prognostic biomarker in PDAC patients who have undergone neoadjuvant therapy followed by an operation. TRG is correlated with RFS, OS and was predictive for the development of liver metastases.