• Dominique L Birrer, Henriette Golcher, Riccardo Casadei, Sarah R Haile, Ralph Fritsch, Saskia Hussung, Thomas B Brunner, Rainer Fietkau, Thomas Meyer, Robert Grützmann, Susanne Merkel, Claudio Ricci, Carlo Ingaldi, Mariacristina Di Marco, Alessandra Guido, Carla Serra, Francesco Minni, Bernhard Pestalozzi, Henrik Petrowsky, Michelle DeOliveira, Wolf O Bechstein, Christiane J Bruns, Christian E Oberkofler, Milo Puhan, Mickaël Lesurtel, Stefan Heinrich, and Pierre-Alain Clavien.
• Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.
• Ann. Surg. 2021 Nov 1; 274 (5): 713720713-720.

ObjectiveThe aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome.Summary Background DataFew underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations.MethodsThree RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards.ResultsA total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters.ConclusionNeoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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