Perioperative management of localized pancreatic ductal adenocarcinoma (PDAC) is guided by resectability criteria that include anatomic, biologic, and clinical factors.[4] In patients with resectable PDAC, the recommended adjuvant regimen is modified FOLFIRINOX (mFOLFIRINOX: 5‑fluorouracil, leucovorin, irinotecan, and oxaliplatin), and many patients are unable to tolerate this standard regimen after surgery.[1][4] Neoadjuvant (preoperative) chemotherapy has been investigated with various regimens, including combinations based on FOLFIRINOX or gemcitabine with nab-paclitaxel; two randomized trials did not demonstrate clear superiority of mFOLFIRINOX/FOLFIRINOX over gemcitabine-nab-paclitaxel (SWOG study S1505) or gemcitabine with radiotherapy (PREOPANC-2).[1][3] In the PRODIGE 24 (adjuvant) study, mFOLFIRINOX had significantly better disease-free survival (21.6 vs. 12.8 months) compared to gemcitabine at a median follow-up of 33.6 months, confirming the efficacy of the regimen in the perioperative setting for some patients.[1] Some studies have investigated the addition of radiotherapy after neoadjuvant chemotherapy and found an increase in pathological complete remission rates (from 0 to 11%) without a clear prolongation of overall survival.[3] Overall, the evidence supports the use of intensive combination chemotherapy in the perioperative setting, however, the results of direct comparisons between regimens are mixed, and postoperative tolerability remains a limiting factor.[3][4]