The influence of neural invasion on survival and tumor recurrence in pancreatic ductal adenocarcinoma - A systematic review and meta-analysis.
OBJECTIVE
To assess the impact of neural invasion/NI on overall survival/OS and tumor recurrence in pancreatic ductal adenocarcinoma/PDAC.


BACKGROUND
NI is a histopathological hallmark of PDAC. Although some studies suggested an important role for NI on OS, disease-free/DFS and progression-free survival/PFS in PDAC, there is still no consensus on the actual role of NI on survival and local recurrence in PDAC.


METHODS
Pubmed, Cochrane library, Ovid and Google Scholar were screened for the terms "pancreatic ductal adenocarcinoma", "pancreatic cancer", "survival", "tumor recurrence" and "perineural invasion". The Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were used for systematic review and meta-analysis. Articles meeting predefined criteria were critically analysed on relevance, and meta-analyses were performed by pooling univariate and multivariate hazard ratios/HR.


RESULTS
A total number of 25 studies on the influence of NI on tumor recurrence, and 121 studies analysing the influence of NI on survival were identified by systematic review. The HR of the univariate (HR 1.88; 95%-CI 1.71-2.07; p < 0.00001) and multivariate meta-analysis (HR 1.68; 95%-CI 1.47-1.92; p < 0.00001) showed a major impact of NI on OS. Likewise, NI was associated with decreased DFS (HR 2.53; 95%-CI: 1.67-3.83; p = 0.0001) and PFS (HR 2.41; 95%-CI: 1.73-3.37: p < 0.00001) multivariate meta-analysis.


CONCLUSIONS
Although the power of this study is limited by missing pathological procedures to assess the true incidence of NI, NI appears to be an independent prognostic factor for OS, DFS and PFS in PDAC. Therefore, NI should be increasingly considered in patient stratification and in the development of novel therapeutic algorithms.
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Stephan
S
Schorn
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Ihsan Ekin
IE
Demir
Institute of Medical Statistics and Epidemiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Bernhard
B
Haller
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Florian
F
Scheufele
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Carmen Mota
CM
Reyes
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Elke
E
Tieftrunk
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Mine
M
Sargut
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Ruediger
R
Goess
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
Helmut
H
Friess
Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany. Electronic address: gueralp.ceyhan@tum.de.
Güralp Onur
GO
Ceyhan
D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
Disease-free-survival; Meta-analysis; Neural invasion; Overall survival; Pancreatic cancer; Recurrence-free survival; Survival; Systematic review