Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis

Abstract Background The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC. Methods A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC). Results Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery. Conclusion Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.