Uson Junior PLS, Kadakia KC, Araujo RLC. Neoadjuvant treatment in resectable pancreatic cancer: Why is upfront surgery so hard to be beaten? World J Clin Oncol 2025; 16(9): 108955 [PMID: 41024839 DOI: 10.5306/wjco.v16.i9.108955]
Corresponding Author of This Article
Raphael L C Araujo, FACS, MD, PhD, Adjunct Professor, Department of Surgery, Universidade Federal de São Paulo, R. Napoleão de Barros, 715, São Paulo 04024-002, Brazil. raphael.l.c.araujo@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Sep 24, 2025; 16(9): 108955 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.108955
Neoadjuvant treatment in resectable pancreatic cancer: Why is upfront surgery so hard to be beaten?
Pedro Luiz Serrano Uson Junior, Kunal C Kadakia, Raphael L C Araujo
Pedro Luiz Serrano Uson Junior, Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05651901, Brazil
Kunal C Kadakia, Department of Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC 28204, United States
Raphael L C Araujo, Department of Surgery, Universidade Federal de São Paulo, São Paulo 04024-002, Brazil
Raphael L C Araujo, Department of Surgery, Hepato-pancreato-biliary Service, Carolinas Medical Center, Atrium Health, Charlotte, NC 28204, United States
Author contributions: Uson Junior PLS, Kadakia KC, and Araujo RLC contributed to the study conception, data preparation, data interpretation, and critical writing.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Raphael L C Araujo, FACS, MD, PhD, Adjunct Professor, Department of Surgery, Universidade Federal de São Paulo, R. Napoleão de Barros, 715, São Paulo 04024-002, Brazil. raphael.l.c.araujo@gmail.com
Received: April 27, 2025 Revised: May 23, 2025 Accepted: August 12, 2025 Published online: September 24, 2025 Processing time: 149 Days and 20.9 Hours
Abstract
Neoadjuvant treatment is being extensively evaluated in pancreatic ductal adenocarcinoma (PDAC). This interest is appropriate given the dismal long-term prognosis for most patients who undergo upfront surgery. Despite prospective, retrospective and randomized trials supporting the role of neoadjuvant therapy in general for PDAC, the long-term benefit specifically for patients with resectable PDAC remains unclear. The phase III PREOPANC trial showed an improvement in overall survival in borderline resectable PDAC with neoadjuvant gemcitabine-based chemoradiation compared to upfront surgery alone, however, no such benefit was observed in the resectable cohort. Notably, three randomized trials (PANACHE01-PRODIGE 48, NORPACT-1, and PREOPANC-2) failed to show a clear improvement in overall survival with a neoadjuvant approach. The ongoing NeoFOL-R, PREOPANC-3, and the Alliance A021806 will help clarify the role of neoadjuvant therapy in resectable PDAC. In this minireview article we summarize the data surrounding neoadjuvant therapy in resectable pancreatic cancer and discuss future considerations of trials in this subgroup.
Core Tip: Upfront surgery remains essential for patients with truly resectable tumors since surgery followed by adjuvant therapy is evidence-based and should not be abandoned. Moreover, current neoadjuvant treatment for resectable lesions with FOLFIRINOX is insufficient due to poor survival outcomes. Better systemic approaches are needed, and germline testing and precision medicine hold promise but are actionable in only a minority of cases, molecular subtyping should be incorporated into future trial designs.
