# Borderline resectable pancreatic ductal adenocarcinoma

Source: https://onco.cc/cancers/borderline-resectable-pdac/  
OnCo record `borderline-resectable-pdac` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Borderline resectable pancreatic cancer touches the big blood vessels behind the pancreas, so an operation straight away would probably leave cancer behind. Chemotherapy first, usually FOLFIRINOX for several months and sometimes radiotherapy, shrinks the edge of the tumour, and patients whose disease has not spread go on to surgery with a better chance of a clean removal.

## Summary

Borderline resectable disease is defined anatomically: tumour contact with the superior mesenteric or portal vein that is reconstructable, abutment of the superior mesenteric artery of 180 degrees or less, or limited contact with the hepatic artery. The MD Anderson, NCCN and international consensus definitions differ in detail and some add biological criteria, such as a very high CA 19-9 or suspicious regional nodes, and conditional criteria such as poor performance status. The point of the category is that upfront surgery leaves a positive margin in a large share of patients and that neoadjuvant treatment selects those who will benefit from a difficult operation.

Neoadjuvant therapy is standard. PREOPANC-1 (2020, long-term follow-up 2022) randomised resectable and borderline patients to gemcitabine-based chemoradiation before surgery or upfront surgery and found more clear-margin resections and better long-term survival, with the benefit concentrated in the borderline group. PREOPANC-2 then compared neoadjuvant FOLFIRINOX with gemcitabine chemoradiation and found no difference, and ESPAC-5 found that neoadjuvant chemotherapy beat immediate surgery for borderline disease. Modified FOLFIRINOX for two to four months is the usual regimen, with gemcitabine plus nab-paclitaxel for less fit patients. The role of radiotherapy after chemotherapy is disputed: ALLIANCE A021501 (2022) stopped its stereotactic radiotherapy arm early because outcomes were worse than with chemotherapy alone, while other groups use conventional or ablative chemoradiation to secure the arterial margin.

After neoadjuvant treatment patients are restaged with CT and CA 19-9; radiological shrinkage is often modest even when the tumour has responded, so surgeons operate on patients with stable disease, falling CA 19-9 and good fitness. Resection with venous reconstruction is routine in specialist centres and arterial resection is done selectively. Pathological response predicts survival, and patients complete a total of six months of chemotherapy after surgery where possible. Germline testing is offered to all, and a BRCA or PALB2 variant argues for a platinum-containing regimen. Trials are adding RAS inhibitors and vaccines to neoadjuvant chemotherapy and testing circulating tumour DNA to decide who should proceed to surgery.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Borderline resectable pancreatic cancer; BRPC; Marginally resectable pancreatic cancer
- Tags: subtype-page; gastrointestinal
- Group: gastrointestinal
- Burden: A fifth or so of newly diagnosed pancreatic cancers touch a major vein or artery enough to make a clear-margin operation uncertain; how many are called borderline depends on the surgeon and the definition used.
- Subtypes: Borderline resectable PDAC with venous involvement only (reconstructable portal or superior mesenteric vein); Borderline resectable PDAC with limited arterial abutment (superior mesenteric or hepatic artery); Biologically borderline PDAC (very high CA 19-9 or suspicious nodes with resectable anatomy); Borderline resectable PDAC converted to resection after FOLFIRINOX; Borderline resectable PDAC that progresses during neoadjuvant therapy (treated as advanced disease)
- Biomarkers: Pancreas-protocol CT with degrees of vessel contact (defines the category); CA 19-9 trend during neoadjuvant chemotherapy (falling levels predict a useful operation); Restaging CT after chemotherapy (stable disease is acceptable; shrinkage is often modest); Germline BRCA1, BRCA2, PALB2 and ATM status (platinum choice); Pathological response grade and margin status after resection; Circulating tumour DNA before surgery (investigational selection marker)

## Standard of care

- Neoadjuvant chemotherapy: Modified FOLFIRINOX for two to four months in fit patients, gemcitabine plus nab-paclitaxel otherwise; restage with CT and CA 19-9 before deciding on surgery (PREOPANC, ESPAC-5). ([FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [PREOPANC-1 / PREOPANC-2](https://onco.cc/trials/preopanc/), [CA 19-9](https://onco.cc/terms/ca19-9/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/))
- Radiotherapy after chemotherapy: Optional; conventional chemoradiation or stereotactic radiotherapy to secure an arterial margin in selected patients, with ALLIANCE A021501 as the caution against routine use. ([Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [MR-guided adaptive radiotherapy](https://onco.cc/technologies/mr-linac/), [Capecitabine](https://onco.cc/drugs/capecitabine/))
- Surgery: Pancreatoduodenectomy or distal pancreatectomy with venous resection and reconstruction where needed, arterial resection only in specialist centres; proceed on stable or improved disease with falling CA 19-9. ([Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/), [Resection margins (R0 / R1 / R2)](https://onco.cc/terms/resection-margins/), [Resectable, borderline resectable and unresectable](https://onco.cc/terms/resectability/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/))
- After surgery: Complete six months of chemotherapy in total, usually with the regimen the tumour responded to. ([FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Capecitabine](https://onco.cc/drugs/capecitabine/))
- Progression during neoadjuvant therapy: Manage as locally advanced or metastatic disease; switch chemotherapy backbone, RAS inhibitor trials, biliary stenting for jaundice. ([NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)](https://onco.cc/drugs/nalirifox/), [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/), [Biliary stenting and drainage](https://onco.cc/technologies/biliary-stenting-drainage/))

## State of the art

- Neoadjuvant chemotherapy is the standard for borderline disease, with modified FOLFIRINOX the usual regimen (PREOPANC, ESPAC-5).
- Venous resection and reconstruction is routine in high-volume centres and no longer a reason to call a tumour unresectable.
- The role of radiotherapy is being redefined after ALLIANCE A021501, with ablative and MR-guided techniques in trials.
- RAS inhibitors and vaccines are entering neoadjuvant trials for the first time.

## Open problems

- Definitions of borderline disease differ between centres, so trial populations are not comparable.
- CT underestimates response after chemotherapy, and there is no validated marker to tell fibrosis from viable tumour before surgery.
- Whether radiotherapy adds anything after modern chemotherapy is unresolved.
- Arterial resection carries high morbidity and its benefit is unproven outside expert centres.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Pancreatic_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Pancreatic_cancer
- NCCN Guidelines: Pancreatic Adenocarcinoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455

## Connected records

- cancers: [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- technologies: [Biliary stenting and drainage](https://onco.cc/technologies/biliary-stenting-drainage/), [CT (computed tomography)](https://onco.cc/technologies/ct/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MR-guided adaptive radiotherapy](https://onco.cc/technologies/mr-linac/), [PDAC organoid pharmacotyping](https://onco.cc/technologies/pdac-organoid-pharmacotyping/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [KRAS](https://onco.cc/targets/kras/)
- drugs: [Autogene cevumeran](https://onco.cc/drugs/autogene-cevumeran/), [Capecitabine](https://onco.cc/drugs/capecitabine/), [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)](https://onco.cc/drugs/nalirifox/)
- companies: [BioNTech](https://onco.cc/companies/biontech/), [Revolution Medicines](https://onco.cc/companies/revolution-medicines/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/)
- terms: [CA 19-9](https://onco.cc/terms/ca19-9/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Locally advanced and locoregional disease](https://onco.cc/terms/locally-advanced/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Resectable, borderline resectable and unresectable](https://onco.cc/terms/resectability/), [Resection margins (R0 / R1 / R2)](https://onco.cc/terms/resection-margins/), [Stereotactic body radiotherapy (SBRT / SABR)](https://onco.cc/terms/sbrt-term/), [Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/)
- trials: [Initial Feasibility Study to Treat Borderline Resectable Pancreatic Cancer With a Planar LDR Source](https://onco.cc/trials/nct02843945/), [PREOPANC-1 / PREOPANC-2](https://onco.cc/trials/preopanc/), [PRODIGE 24 / CCTG PA6](https://onco.cc/trials/prodige-24/), [Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC)](https://onco.cc/trials/nct07252232/)
- people: [Albert C. Koong](https://onco.cc/people/albert-koong/), [Eileen M. O'Reilly](https://onco.cc/people/eileen-oreilly/), [Jürgen Weitz](https://onco.cc/people/jurgen-weitz/), [Marc G. Besselink](https://onco.cc/people/marc-besselink/), [Richard Schulick](https://onco.cc/people/richard-schulick/), [Theodore S. Hong](https://onco.cc/people/theodore-hong/)
- key papers: [Conroy 2011: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer (PRODIGE 4/ACCORD 11)](https://onco.cc/key-papers/paper-conroy-folfirinox-pancreatic-nejm-2011/)
- ideas: [Grow each trial patient's tumour as organoids to decide which platform arm opens next](https://onco.cc/ideas/idea-tr2-organoid-coclinical-arms/), [RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable](https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/)

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