Does Pancreatic Fistula Affect Long-Term Survival after Resection for Pancreatic Cancer? A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: The real influence of postoperative pancreatic fistula (POPF) on long-term survival after pancreatic cancer resection is unclear. The purpose of the present study was therefore to conduct a systematic review and meta-analysis of the impact of POPF on the disease-free and overall survival of patients with pancreatic cancer. Our results highlighted that clinically relevant POPF after surgery for PDAC seems to be significantly associated with shorter DFS and OS. Confirmation, with future studies, of a negative impact of POPF on survival may encourage the widespread use of risk-stratification tools for assessing fistula, centralization of patients, and probably a closer oncological follow-up. ABSTRACT: Background: The impact of postoperative pancreatic fistula (POPF) on survival after resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods: The MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting on survival in patients with and without POPF. A meta-analysis was performed to investigate the impact of POPF on disease-free survival (DFS) and overall survival (OS). Results: Sixteen retrospective cohort studies concerning a total of 5019 patients with an overall clinically relevant POPF (CR-POPF) rate of 12.63% (n = 634 patients) were considered. Five of eleven studies including DFS data reported higher recurrence rates in patients with POPF, and one study showed a higher recurrence rate in the peritoneal cavity. Six of sixteen studies reported worse OS rates in patients with POPF. Sufficient data for a meta-analysis were available in 11 studies for DFS, and in 16 studies for OS. The meta-analysis identified a shorter DFS in patients with CR-POPF (HR 1.59, p = 0.0025), and a worse OS in patients with POPF, CR-POPF (HR 1.15, p = 0.0043), grade-C POPF (HR 2.21, p = 0.0007), or CR-POPF after neoadjuvant therapy. Conclusions: CR-POPF after resection for PDAC is significantly associated with worse overall and disease-free survival.