Introduction The management of pancreatic ductal adenocarcinoma (PDAC) has increasingly shifted toward the use of neoadjuvant therapy (NAT) before surgical resection. NAT aims to improve resectability, treat micrometastatic disease early, and select patients with favourable tumour biology.
Introduction
The management of pancreatic ductal adenocarcinoma (PDAC) has increasingly shifted toward the use of neoadjuvant therapy (NAT) before surgical resection. NAT aims to improve resectability, treat micrometastatic disease early, and select patients with favourable tumour biology. However, an important unresolved question is the role of adjuvant therapy (AT) after patients have already received NAT followed by surgery. It remains unclear whether additional postoperative chemotherapy provides a survival benefit and how the type and duration of NAT influence the need for AT.
Summary
This multicenter study analysed 651 patients with PDAC who received NAT followed by surgical resection between 2010 and 2019. Patients were categorised according to the NAT regimen:
Gemcitabine-based NAT: 200 patients (30.7%)
5-fluorouracil (5-FU)–based NAT: 362 patients (56%)
Switched NAT regimen: 89 patients (13.7%)
Key findings:
Median overall survival (OS):
Gemcitabine-based NAT: 19 months
5-FU–based NAT: 26 months
Switched regimen: 21 months
5-FU–based NAT was associated with improved survival compared with gemcitabine-based NAT (HR 0.81, p = 0.04).
The optimal NAT duration was approximately 3.6 months.
Adjuvant therapy significantly improved survival overall (HR 0.61, p < 0.001).
However, the survival benefit of AT diminished when NAT duration exceeded 5 months, suggesting that prolonged preoperative treatment may reduce the need for postoperative chemotherapy.
Clinical Implication
In patients undergoing resection for PDAC after NAT, 5-FU–based neoadjuvant regimens appear superior to gemcitabine-based therapy. Adjuvant chemotherapy remains beneficial, particularly when preoperative NAT duration is short, highlighting the importance of personalising postoperative therapy based on prior treatment exposure.
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