Survival Outcomes in Nonmetastatic pT4 Pancreatic Ductal Adenocarcinoma: A SEER Database Analysis Comparing Neoadjuvant Therapy and Upfront Surgery with Propensity Score Matching.

BACKGROUND

Given the increasing use of neoadjuvant therapy (NAT) for localized pancreatic ductal adenocarcinoma (PDAC), this study aimed to evaluate the survival outcomes of patients with pathological T4 (pT4) PDAC who received NAT followed by resection versus those who underwent upfront surgery.

METHODS

We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to compare survival outcomes of T4N0-XM0 PDAC patients in NAT and upfront surgery groups. Propensity score matching (PSM) was used to balance baseline characteristics. Kaplan-Meier curves and Cox regression analyses were employed to assess overall survival (OS) and identify prognostic factors. Subgroup analyses were conducted within the NAT cohort to determine the impact of different NAT modalities, adjuvant therapy (AT), lymph node yield (LNY), and lymph node ratio (LNR) on OS in this cohort.

RESULTS

Of 8950 pT4 PDAC patients identified, 654 met the inclusion criteria (241 NAT vs. 413 upfront surgery). After PSM, 152 well-matched pairs remained. The median survival times were 26 months for NAT and 12 months for upfront surgery (P < 0.001). NAT was associated with significantly improved OS at all time points. Multivariate analysis identified NAT (P < 0.001) and AT (P = 0.002) as independent prognostic factors of improved OS. No significant OS difference was observed between neoadjuvant chemotherapy and chemoradiotherapy or between NAT with and without AT. Subgroup analysis revealed no significant difference in OS based on LNY cutoff values in either node-negative or node-positive cohorts but worse OS in node-positive patients with LNR ≥ 0.1 (P = 0.003).

CONCLUSIONS

NAT followed by resection significantly improves OS in patients with pT4 PDAC, even in the absence of complete pathological downstaging.