Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and Meta-Analysis

Background: Prognostic markers for overall survival in resected pancreatic ductal adenocarcinoma are well established but remain unclear following neoadjuvant therapy. This systematic review and meta-analysis aimed to determine factors associated with overall survival following neoadjuvant therapy in resected pancreatic ductal adenocarcinoma. Methods: The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from January 2010 until May 2024. Studies that reported univariable and multivariable hazard ratios were included if patients underwent neoadjuvant therapy and resection for localized pancreatic ductal adenocarcinoma. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. Results: Among 2208 unique articles identified by the search, 92 were included in the meta-analysis. Of these, 85 were of "good"and 7 of "poor"quality. The neoadjuvant therapy regimen was described in 84 studies of which 62 included patients treated with FOLFIRINOX. Margin status, nodal disease, American Joint Committee on Cancer (AJCC) T-stage, and normalization of cancer antigen 19-9 (CA19-9) after neoadjuvant therapy were prognostic for overall survival, whereas age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN substages was not statistically significant in the multivariable model. Neoadjuvant FOLFIRINOX was associated with better survival than other regimens. Conclusions: This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after neoadjuvant therapy as prognostic factors for overall survival in patients with resected localized pancreatic ductal adenocarcinoma following neoadjuvant therapy.