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The Dutch trial testing whether treating before surgery beats operating first. Chemoradiation first fell short at the primary analysis but won at five years, with one in five patients alive against one in fifteen.
PREOPANC-1 randomised 246 patients between 2013 and 2017. The primary analysis (JCO 2020) gave median OS 16.0 vs 14.3 months (HR 0.78, p 0.096), short of significance, with a higher R0 resection rate (71% vs 40%) and better disease-free survival; the long-term analysis (JCO 2022, median follow-up 59 months) gave HR 0.73 (p 0.025) and 5-year OS 20.5% vs 6.5%, consistent in resectable and borderline patients. Its successor PREOPANC-2 (Lancet Oncology 2025) found neoadjuvant FOLFIRINOX no better than this regimen (21.9 vs 21.3 months), and PREOPANC-3 and ALLIANCE A021806 now test perioperative against adjuvant mFOLFIRINOX, while NORPACT-1 argued against neoadjuvant treatment for clearly resectable tumours; borderline-resectable disease is generally treated neoadjuvantly.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
246 enrolled.
51 of 72 · 37 of 92
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (long-term)primary | Neoadjuvant chemoradiotherapy, 5-year OS | 119 | 20.5% | 0.73 (0.56 to 0.96) | 0.025 | link |
| Upfront surgery, 5-year OS | 127 | 6.5% | ||||
| Overall survival (primary analysis, intention to treat) | Neoadjuvant gemcitabine chemoradiotherapy, surgery, adjuvant gemcitabine | 119 | 16 months | 0.78 (0.58 to 1.05) | 0.096 | link |
| Upfront surgery, adjuvant gemcitabine | 127 | 14.3 months | ||||
| R0 resection rate among resected patients | Neoadjuvant chemoradiotherapy | 72 | 71% | - | <0.001 | link |
| Upfront surgery | 92 | 40% |
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.
Neoadjuvant treatment is now the standard for borderline resectable pancreatic cancer, and PREOPANC is the trial guidelines cite; the follow-on PREOPANC-2 tested FOLFIRINOX in the same setting.
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 NORPACT-1, Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial, Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed, Resectable pancreatic ductal adenocarcinoma.
Shares Dutch Pancreatic Cancer Group, Marc G. Besselink, Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial, Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial.
Shares Alliance A021806, Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer, Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial, Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial.
Shares PREOPANC-3, Alliance A021806, Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer, Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed.
Shares PREOPANC-2, Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed, Borderline resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares Alliance A021806, NORPACT-1, Neoadjuvant / adjuvant / perioperative, Resectable pancreatic ductal adenocarcinoma.
Shares Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial, Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed, Neoadjuvant / adjuvant / perioperative, Resectable pancreatic ductal adenocarcinoma.
Shares Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer, Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed, Borderline resectable pancreatic ductal adenocarcinoma, Resectable pancreatic ductal adenocarcinoma.