Neoadjuvant Therapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: A Systemic Review and Meta-Analysis

Chandler A Annesi; Michelle Holland; M Chandler McLeod; Sushanth Reddy; J Bart Rose; Vikas Dudeja; Martin J Heslin; Annabelle L Fonseca

doi:10.1016/j.jss.2025.04.042

Neoadjuvant Therapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: A Systemic Review and Meta-Analysis

J Surg Res. 2025 Jul:311:221-231. doi: 10.1016/j.jss.2025.04.042. Epub 2025 May 28.

Authors

Chandler A Annesi¹, Michelle Holland¹, M Chandler McLeod¹, Sushanth Reddy², J Bart Rose², Vikas Dudeja², Martin J Heslin², Annabelle L Fonseca³

Affiliations

¹ Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
² Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
³ Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: afonseca@uabmc.edu.

PMID: 40440879
PMCID: PMC12324811 (available on 2026-05-28)
DOI: 10.1016/j.jss.2025.04.042

Abstract

Introduction: It is accepted that patients with pancreatic cancer are best treated by a combination of surgical resection and systemic chemotherapy; the optimal sequence remains debated. There are ongoing trials on survival benefit of neoadjuvant therapy (NAT) compared to upfront surgery (UFS) in patients with resectable and borderline resectable pancreatic cancer; new and updated data must be analyzed for continued understanding of results.

Methods: A search of multiple databases was performed for randomized controlled trials (RCTs) comparing NAT with UFS for resectable and borderline resectable pancreatic cancer. The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome of interest was overall survival (OS) by intention-to-treat; subgroup analysis was also performed for resectable disease only. Meta-analyses were completed using random-effects models.

Results: There were 13,406 records screened for inclusion; 51 were retrieved for further review; 34 were assessed for eligibility. Ten RCTs were included with 1340 patients split almost equally between NAT and UFS. Gemcitabine-based NAT was used in all but two RCTs. There was a significant improvement in median OS for NAT compared to UFS (hazard ratio 0.78, 95% confidence interval 0.61-0.99; P = 0.04; I² = 43%). In the subgroup analysis of patients with resectable pancreatic cancer, there was no improvement in survival (hazard ratio 0.86, 95% confidence interval 0.59-1.26; P = 0.36; I² = 49%).

Conclusions: In this meta-analysis of prospective RCTs assuming intention-to-treat, NAT was associated with improvement in OS relative to UFS in patients with resectable and borderline resectable pancreatic cancer. Given the heterogeneity of the NAT regimens studied in this meta-analysis and recruitment challenges, additional analyses are warranted to confirm these findings and to determine the optimal sequencing of treatment modalities.

Keywords: Borderline resectable; Meta-analysis; Neoadjuvant therapy; Pancreatic cancer; Resectable; Systematic review; Upfront surgery.

Publication types

Systematic Review
Meta-Analysis
Comparative Study
Research Support, N.I.H., Extramural

MeSH terms

Chemotherapy, Adjuvant
Humans
Neoadjuvant Therapy* / methods
Pancreatectomy* / methods
Pancreatic Neoplasms* / mortality
Pancreatic Neoplasms* / therapy
Randomized Controlled Trials as Topic
Treatment Outcome

Abstract

Publication types

MeSH terms

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