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Giving chemotherapy before the operation is standard when the tumour is borderline operable, but for tumours that can be removed straight away two trials have failed to show it beats operating first. Two more, one Dutch and one American, are directly comparing chemotherapy before and after surgery with chemotherapy after alone; the proposal is to wait for them and to pool them.
PREOPANC (2020) missed its primary endpoint (16.0 versus 14.3 months) but raised R0 resection from 40 to 71 percent and showed a five-year benefit in 2022; ESPAC-5 and Alliance A021501 supported neoadjuvant treatment for borderline resectable disease. For resectable disease, NORPACT-1 (2024) did not favour neoadjuvant FOLFIRINOX over upfront surgery and PREOPANC-2 (2025, 375 patients) found neoadjuvant FOLFIRINOX no better than gemcitabine chemoradiotherapy (21.9 versus 21.3 months), with neither trial using the current adjuvant standard of six months of modified FOLFIRINOX as comparator. The argument for neoadjuvant treatment for all is that a third of patients never receive adjuvant chemotherapy after a Whipple operation and that early systemic treatment tests biology before a major operation; the argument against is that FOLFIRINOX before surgery delays or prevents the operation in patients who progress and that PRODIGE 24 already delivers a median of 53.5 months in those who get it. PREOPANC-3 (378 estimated, primary completion January 2027) and Alliance A021806 (358, December 2028) compare perioperative with adjuvant modified FOLFIRINOX and are the trials that can settle it; a pre-planned pooled analysis, with resection rate, R0 rate and receipt of all planned chemotherapy as secondary endpoints, would give the answer more power than either alone.
Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.
Upfront surgery followed by adjuvant chemotherapy remains standard for clearly resectable pancreatic cancer; neoadjuvant treatment belongs in trials or borderline disease.
The best survival ever recorded in a pancreatic cancer trial, and the benchmark every perioperative trial (PREOPANC-3, Alliance A021806) and every adjuvant RAS inhibitor or vaccine trial (RASolute 304, IMCODE003) now has to beat or add to.
Neoadjuvant modified FOLFIRINOX without routine radiotherapy became the reference approach for borderline resectable disease in North America; radiotherapy is reserved for selected patients or trials.
The trial that made neoadjuvant treatment standard for borderline resectable disease and opened the still unresolved question for resectable disease, which PREOPANC-2, NORPACT-1, PREOPANC-3 and Alliance A021806 inherited.
Shares Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial, PRODIGE 24 / CCTG PA6, FOLFIRINOX / mFOLFIRINOX, Neoadjuvant / adjuvant / perioperative and the tag pancreatic-evidence.
Shares Resectable, borderline resectable and unresectable, Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Neoadjuvant / adjuvant / perioperative, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma, Cytotoxic chemotherapy and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma, Cytotoxic chemotherapy, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Trial design, endpoints and cost, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable, FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares PRODIGE 24 / CCTG PA6, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Resectable pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.