Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and meta-analysis.

Ammar A Javed, Christopher L Wolfgang, Jin He, Asad Saulat Fatimi, Omar Mahmud, Marc G Besselink, Alyssar Habib, Mahip Grewal, Nabiha Mughal, Lois Daamen

Journal: Journal of the National Cancer Institute 2025;117(5):840-867

PMID: 39563429

Abstract

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.

© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Address: New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States.; Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam 1007 MB, the Netherlands.; Cancer Center Amsterdam, Amsterdam 1007 MB, the Netherlands.; New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States.; New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States.; Medical College, Aga Khan University, Karachi 74800, Pakistan.; Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States.; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands.; Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam 1007 MB, the Netherlands.; Cancer Center Amsterdam, Amsterdam 1007 MB, the Netherlands.
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