Multimodal Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma (PDAC) With Vascular Involvement: What Is the Impact of Radiation on Perioperative Outcomes, Local Control, and Survival?

OBJECTIVES: Neoadjuvant chemoradiation for PDAC with vascular invasion remains understudied. The aim of this study is to compare neoadjuvant chemotherapy with chemoradiation (NAC + CRT) versus neoadjuvant chemotherapy (NAC) for PDAC with vascular involvement. METHODS: The National Cancer Database was reviewed between 2018 and 2023, including patients with T4 PDAC initiating NAC or NAC + CRT. The primary outcome of overall survival (OS) was examined among unresected and resected cohorts. Secondary outcomes included pathologic complete response (pCR), node-negative (ypN0) pathology, and R0 resection. Multilevel logistic and Cox models were fit to identify factors associated with outcomes. RESULTS: In total, 2950 patients met inclusion, of which 1407 (47.7%) underwent NAC + CRT. In total, 1291 (44.4%) underwent surgery. Use of NAC + CRT declined by 2.8%/year (p < 0.001). Compared with NAC, use of NAC + CRT was associated with R0 resection (OR: 0.62, 95% CI: [0.43, 0.89], p = 0.010) and ypN0 (OR: 2.19, 95% CI: [1.63, 2.93], p < 0.001) but not pCR (OR: 1.78, 95% CI: [0.99, 3.20], p = 0.056). NAC + CRT was associated with improved OS among the full cohort (hazard ratio [HR]: 0.67, 95% CI: [0.60, 0.74], p < 0.001) but not the resected cohort (HR: 0.98, 95% CI: [0.81, 1.19], p = 0.848). CONCLUSIONS: Neoadjuvant chemoradiation for T4 PDAC yielded mixed effects on local response with no survival difference among patients undergoing resection.