# PREOPANC-1

Source: https://onco.cc/trials/preopanc/  
OnCo record `preopanc` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Trial
- Status: mixed
- Last checked: 2026-09-06
- Also known as: PREOPANC; PREOPANC-1; PREOPANC 1
- Registry id: NTR3709
- Phase: 3
- Setting: Resectable and borderline-resectable PDAC at 16 Dutch centres: neoadjuvant gemcitabine-based chemoradiation (36 Gy in 15 fractions), surgery and adjuvant gemcitabine vs upfront surgery and adjuvant gemcitabine
- Sponsor: Dutch Pancreatic Cancer Group
- Enrolled: 246
- Result: 5-year OS 20.5% vs 6.5% (HR 0.73, p 0.025); primary analysis median OS 16.0 vs 14.3 months (HR 0.78, p 0.096).
- Outcomes: Overall survival (long-term): Neoadjuvant chemoradiotherapy, 5-year OS 20.5% vs Upfront surgery, 5-year OS 6.5%, HR 0.73; Overall survival (primary analysis, intention to treat): Neoadjuvant gemcitabine chemoradiotherapy, surgery, adjuvant gemcitabine 16 months vs Upfront surgery, adjuvant gemcitabine 14.3 months, HR 0.78; R0 resection rate among resected patients: Neoadjuvant chemoradiotherapy 71% vs Upfront surgery 40%
- Replication: Supported by PREOPANC-2 and ALLIANCE A021806 in favour of neoadjuvant therapy in (borderline) resectable disease.

## Notes

- PREOPANC-1 design (JCO 2020): 246 patients at 16 Dutch centres randomised between April 2013 and July 2017 to three cycles of gemcitabine with 36 Gy in 15 fractions during the second, surgery and four adjuvant cycles, or immediate surgery and six adjuvant cycles. Primary analysis: median overall survival 16.0 against 14.3 months (hazard ratio 0.78; p 0.096), resection rate 61 against 72 percent, R0 rate 71 against 40 percent, serious adverse events 52 against 41 percent. Long-term analysis (JCO 2022, median follow-up 59 months): hazard ratio 0.73 (0.56 to 0.96; p 0.025), median 15.7 against 14.3 months, five-year survival 20.5 against 6.5 percent, consistent in resectable and borderline subgroups. PREOPANC-2 (2025) then compared neoadjuvant FOLFIRINOX with this regimen and found no difference (21.9 against 21.3 months).

## Sources

- PREOPANC-1 primary analysis, JCO 2020 (NTR3709): https://doi.org/10.1200/JCO.19.02274
- PREOPANC-1 long-term results, JCO 2022: https://doi.org/10.1200/JCO.21.02233

## Connected records

- cancers: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer](https://onco.cc/terms/neoadjuvant-versus-upfront-surgery-pancreatic/)
- drugs: [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- companies: [Dutch Pancreatic Cancer Group](https://onco.cc/companies/dpcg/)
- trials: [Alliance A021806](https://onco.cc/trials/alliance-a021806/), [NORPACT-1](https://onco.cc/trials/norpact-1/), [PREOPANC-2](https://onco.cc/trials/preopanc-2/), [PREOPANC-3](https://onco.cc/trials/preopanc-3/)
- people: [Marc G. Besselink](https://onco.cc/people/marc-besselink/)
- key papers: [Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial](https://onco.cc/key-papers/paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025/), [PREOPANC long-term results: neoadjuvant gemcitabine-based chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer](https://onco.cc/key-papers/paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022/), [Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial](https://onco.cc/key-papers/paper-preopanc-preoperative-chemoradiotherapy-jco-2020/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work](https://onco.cc/roadmaps/surgery-roadmap/)
- ideas: [Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed](https://onco.cc/ideas/idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease/)

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