# Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer

Source: https://onco.cc/terms/neoadjuvant-versus-upfront-surgery-pancreatic/  
OnCo record `neoadjuvant-versus-upfront-surgery-pancreatic` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

For pancreatic cancers that look removable, doctors debate whether to operate at once and give chemotherapy afterwards, or to give chemotherapy first. Trials show chemotherapy first helps when the tumour is borderline, touching the big vessels, but it is not yet proven better for clearly removable tumours, where the largest trial found no gain and a US trial is still running.

## Summary

The case for treatment first: micrometastatic disease is present in most patients, half never receive the planned adjuvant chemotherapy because of slow recovery or early relapse, response can be tested before a major operation, and shrinkage away from the vessels raises the R0 rate. The case for surgery first: the only cure is removed while it is still removable, and 10 to 20 percent progress during neoadjuvant treatment. The evidence. PREOPANC (16 Dutch centres, 246 patients with resectable or borderline resectable disease) randomised gemcitabine-based chemoradiotherapy before surgery against surgery first, both with adjuvant gemcitabine; the primary analysis missed, but at a median of 59 months overall survival favoured neoadjuvant treatment (hazard ratio 0.73) with a five-year survival of 20.5 percent against 6.5 percent, despite a median difference of only 1.4 months (Versteijne 2022). A meta-analysis of seven randomised trials (938 patients, all with gemcitabine-based neoadjuvant arms and none with adjuvant FOLFIRINOX) found neoadjuvant therapy improved survival overall (hazard ratio 0.66, median 19 to 29 months), significantly in borderline resectable disease (0.61) but not in resectable disease (0.77, not significant), with high certainty for the overall result (van Dam 2022). NORPACT-1, the Nordic trial of neoadjuvant FOLFIRINOX against surgery first with adjuvant chemotherapy in resectable head cancer, did not show a survival benefit (its paper is in this record's key papers); PREOPANC-2 found neoadjuvant FOLFIRINOX no better than neoadjuvant gemcitabine chemoradiotherapy (the PREOPANC trial record). Alliance A021806, a phase III trial of perioperative against adjuvant mFOLFIRINOX in resectable disease, has enrolled 358 patients, is active but no longer recruiting, has a primary completion date of December 2028 and had posted no results when this was written (design paper 2024; ClinicalTrials.gov NCT04340141). Guidance: NICE NG85 (2018) says neoadjuvant therapy for borderline resectable and for resectable disease should only be considered within a clinical trial (1.8.1, 1.8.2) and offers adjuvant gemcitabine plus capecitabine after resection (1.8.6); the NCCN guideline prefers neoadjuvant therapy for borderline resectable disease and allows it for resectable disease with high-risk features (a very high CA 19-9, a large tumour, suspicious nodes, severe symptoms). The RAS inhibitor idea linked from the parent record proposes testing the new drugs in this window.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: Surgery-first versus chemotherapy-first in pancreatic cancer; Perioperative chemotherapy pancreatic cancer; Total neoadjuvant therapy for pancreatic cancer; Preoperative chemotherapy pancreatic cancer; PREOPANC question; NORPACT question
- Tags: gi; pancreatic

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Neoadjuvant_therapy
- Versteijne, J Clin Oncol 2022: PREOPANC long-term results, neoadjuvant chemoradiotherapy versus upfront surgery: https://doi.org/10.1200/jco.21.02233
- van Dam, Eur J Cancer 2022: neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer, meta-analysis of 7 trials: https://doi.org/10.1016/j.ejca.2021.10.023
- Ann Surg Oncol 2024: Alliance A021806, phase III perioperative versus adjuvant chemotherapy for resectable pancreatic cancer (design): https://doi.org/10.1245/s10434-024-15817-5
- ClinicalTrials.gov NCT04340141: Alliance A021806 (active, not recruiting; 358 enrolled; primary completion December 2028; no results posted, read 24 Sept 2026): https://clinicaltrials.gov/study/NCT04340141
- NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8): https://www.nice.org.uk/guidance/ng85/chapter/Recommendations
- NCCN Guidelines: Pancreatic Adenocarcinoma (resectability criteria): https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455

## Connected records

- ideas: [RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable](https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/)
- cancers: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Downstaging and conversion therapy](https://onco.cc/terms/downstaging/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [R0 and R1 margins in pancreatic cancer: the 1 mm rule and standardised specimen reporting](https://onco.cc/terms/r0-r1-margin-pancreatic/), [Resectability classes for pancreatic cancer (NCCN anatomical criteria and the 2017 international consensus)](https://onco.cc/terms/nccn-resectability-criteria-pancreatic/), [Resectable, borderline resectable and unresectable](https://onco.cc/terms/resectability/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- trials: [NORPACT-1](https://onco.cc/trials/norpact-1/), [PREOPANC-1](https://onco.cc/trials/preopanc/), [PRODIGE 24 / CCTG PA6](https://onco.cc/trials/prodige-24/)

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