Surgical Outcomes Following Neoadjuvant Treatment for Locally Advanced and Borderline Resectable Pancreatic Ductal Adenocarcinoma

Objective: To assess overall survival (OS), compare the effects of neoadjuvant treatment, and describe surgical outcomes for patients undergoing pancreatic resection following chemotherapy and/or chemoradiotherapy (CRT) for borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).

Background: We approach BR/LA PDAC using chemotherapy followed by selective CRT to the primary site of disease where either the surgical margin remains radiologically threatened following chemotherapy or as a further downstaging treatment.

Methods: Retrospective study of patients between December 2005 and June 2023 at the Royal Marsden Hospital, London, United Kingdom.

Results: A total of 54 patients were included. The OS between R1 and R0 patients was significantly different: 7.5 versus 23 versus 42 versus 51 months for R1 chemo, R1 chemo and CRT, R0 chemo and R0 chemo, and CRT groups, respectively, P < 0.001. Similarly, 9 versus 18 versus 42 versus 41 months for N1 chemo, N1 chemo and CRT, N0 chemo and N0 chemo, and CRT groups, respectively, P = 0.0026. Multivariable Cox regression model demonstrated that perineural invasion (hazard ratio: 2.88, 95% confidence interval: 1.06-7.81; P = 0.038) and perivascular invasion (PVI) (HR: 2.76, 95% CI: 1.24-6.13; P = 0.013) were associated with significantly worse OS. Chemo and CRT conferred OS benefit compared to chemo only (7 vs 23 months, P = 0.004) in PVI-positive patients.

Conclusions: Neoadjuvant chemotherapy followed by CRT compared to chemotherapy alone for resected BD and LA PDAC was demonstrated to significantly improve median OS, in particular, in patients with R1 resection margins, ypN1 nodal status, and perivascular invasion.