Perineural and Lymphovascular Invasion in Resected Pancreatic Ductal Adenocarcinoma: A High-Risk Subgroup That Could Benefit from Adjuvant Radiotherapy.

Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) are adverse prognostic factors in pancreatic ductal adenocarcinoma (PDAC). Their concurrence may warrant intensified adjuvant therapy. This study investigated the prognostic impact of concurrent PNI and LVI and the potential benefit of adjuvant radiotherapy. Methods: A retrospective analysis was conducted in patients who underwent pancreaticoduodenectomy for PDAC (2015-2023). Patients were grouped as PNI only, concurrent PNI and LVI, or neither. Clinicopathological features and survival outcomes were compared. In the concurrent PNI and LVI subgroup, the effect of adjuvant radiotherapy was analyzed according to margin status (R0 vs. R1). Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Results: Eighty-eight patients were included. Recurrence occurred in 83.0%, with locoregional recurrence in 30.1%. Median DFS was 10.5 months and OS was 19.0 months; four patients (4.5%) survived ≥5 years. Concurrent PNI and LVI was observed in 55.7% and independently predicted reduced DFS (HR 3.23; p = 0.002) and OS (HR 2.34; p = 0.02), whereas adjuvant radiotherapy was associated with prolonged DFS (HR 0.48; p = 0.008). Among R0-resected patients with concurrent PNI and LVI, radiotherapy reduced locoregional recurrence (6.3% vs. 46.7%; p = 0.01) and improved median DFS (10.0 vs. 7.0 months; p = 0.04). Conclusions: Patients with concurrent PNI and LVI are a high-risk subgroup of PDAC. Adjuvant radiotherapy after R0 resection may improve DFS and reduce recurrence in these patients.