Manojlovic N, Savic G, Manojlovic S. Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how. World J Gastrointest Surg 2024; 16(5): 1223-1230 [PMID: 38817288 DOI: 10.4240/wjgs.v16.i5.1223]
Corresponding Author of This Article
Nebojsa Manojlovic, PhD, Associate Professor, Clinic for Gastroenterology and Hepatology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Crnotravska 17, Belgrade 11000, Serbia. nebojsa.manojlovic1@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
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/
Nebojsa Manojlovic, Clinic for Gastroenterology and Hepatology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade 11000, Serbia
Goran Savic, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade 11000, Serbia
Stevan Manojlovic, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Author contributions: Manojlovic N, Savic G, and Manojlovic S contributed to this paper; Manojlovic N designed the overall concept and outline of the manuscript, and drafted and edited the manuscript; Savic G and Manojlovic S contributed to the discussion and design of the manuscript, and made critical revision of the manuscript and contributed to the review of literature.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Nebojsa Manojlovic, PhD, Associate Professor, Clinic for Gastroenterology and Hepatology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Crnotravska 17, Belgrade 11000, Serbia. nebojsa.manojlovic1@gmail.com
Received: December 28, 2023 Revised: March 13, 2024 Accepted: April 22, 2024 Published online: May 27, 2024 Processing time: 146 Days and 10.1 Hours
Abstract
Pancreatic ductal adenocarcinoma (PDAC), which is notorious for its aggressiveness and poor prognosis, remains an area of great unmet medical need, with a 5-year survival rate of 10% - the lowest of all solid tumours. At diagnosis, only 20% of patients have resectable pancreatic cancer (RPC) or borderline RPC (BRPC) disease, while 80% of patients have unresectable tumours that are locally advanced pancreatic cancer (LAPC) or have distant metastases. Nearly 60% of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy (CHT) because of postoperative complications and early cancer recurrence. An important paradigm shift to achieve better outcomes has been the sequence of therapy, with neoadjuvant CHT preceding surgery. Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers: RPC, BRPC, and LAPC. The main goal of neoadjuvant treatment (NAT) is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT, reducing tumour volume before surgery to improve the rate of margin-negative resection (R0 resection, a microscopic margin-negative resection), reducing the rate of positive lymph node occurrence at surgery, providing early treatment of occult micrometastatic disease, and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria. In this editorial, we summarize evidence concerning NAT of PDAC, providing insights into future practice and study design. Future research is needed to establish predictive biomarkers, measures of therapeutic response, and multidisciplinary strategies to improve patient-centered outcomes.
Core Tip: Pancreatic ductal adenocarcinoma, which is notorious for its aggressiveness and poor prognosis, remains an area of great unmet medical need. The most important determinant of survival is surgical resection. Nearly 60% of patients who undergo upfront surgery for resectable tumours are unable to receive adequate adjuvant chemotherapy (CHT). An important paradigm shift to achieve better outcomes has been the sequence of therapy, with neoadjuvant CHT preceding surgery. Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers: Resectable, borderline-resectable and unresectable locally advanced tumours. In the development of new neoadjuvant and induction strategies, the distinct molecular and biological characteristics of the various pancreatic cancer subgroups need to be integrated to optimize the selection and sequencing of both established and novel treatment modalities that may improve survival outcomes.
