Two-center retrospective cohort study of neoadjuvant chemotherapy with or without radiotherapy for pancreatic ductal adenocarcinoma

The role of preoperative radiotherapy (RT) after neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC) is controversial. A retrospective propensity score-matched cohort study at two centers (Massachusetts General Hospital, Boston, USA, and San Raffaele Scientific Insitute, Milan, Italy) evaluated whether addition of RT tot NACT was associated with improved oncologic outcomes. The study included 800 patients undergoing PDAC resection between 2015 and 2023 after NACT plus RT (n=438) or NACT alone (n=362). Aftrer matching, 226 patients per group were analyzed. The median follow-up was 44 months. Addition of RT was associated with higher rates of pathologic complete response (6.6% versus 4.4%). Recurrence patterns were similar, with distant recurrence as the predominant first site of failure in both groups (51.3% versus 52.2%). In competing risk analysis, the cumulative incidence of locoregional recurrence did not differ (sHR 0.90; p=0.71). RT was not associated with improved event-free survival (HR 1.10; p=0.38) or overall survival (HR 1.02; p=0.34). The authors conclude that these findings highlight the limited impact of locoregional control in a disease driven by systemic progression.