# Locally advanced unresectable pancreatic ductal adenocarcinoma

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

## TL;DR

Locally advanced pancreatic cancer has grown around the arteries or veins behind the pancreas so that it cannot be removed, but it has not spread to other organs. Chemotherapy is the main treatment, joined in 2026 by a device that delivers electric fields to the tumour; radiotherapy controls pain and local growth, and a minority of tumours shrink enough to be operated on after all.

## Summary

Locally advanced pancreatic ductal adenocarcinoma is defined by encasement of the superior mesenteric or coeliac artery beyond 180 degrees, an unreconstructable portal or superior mesenteric vein, or aortic involvement, with no metastases on CT. It behaves as a systemic disease: most patients who die of it have metastases at the time, which is why chemotherapy is the first treatment and why trials of adding local therapy have struggled to show a survival gain. Patients present with pain, weight loss, jaundice and new diabetes, and supportive care (biliary stenting, pancreatic enzymes, nutrition, coeliac plexus block for pain) is part of the treatment from the start.

Induction chemotherapy is modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, extrapolated from the metastatic trials and supported by the NEOLAP and other phase 2 studies. Consolidation chemoradiation after induction did not lengthen survival in LAP07 (2016) but did delay local progression and reduce the need for further chemotherapy, so it remains an option, along with stereotactic body radiotherapy and MR-guided ablative radiotherapy, which deliver high doses to tumours abutting the bowel. Irreversible electroporation and other ablative techniques are used in a few centres without randomised evidence. PANOVA-3 (2025) was the first positive phase 3 trial in this stage in a decade: adding tumour treating fields to gemcitabine plus nab-paclitaxel lengthened survival, and the device was approved in 2026.

After induction, patients are restaged and a minority with stable or responding disease, especially those whose CA 19-9 has normalised, are explored with a view to resection, sometimes with arterial resection; this conversion surgery is the goal of the whole strategy but remains uncommon. Trials in this stage now add RAS inhibitors, stroma-directed agents and immunotherapy combinations to chemotherapy and test whether ablative radiotherapy can replace surgery for tumours that will never be removable.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Locally advanced pancreatic cancer; LAPC; Unresectable non-metastatic pancreatic cancer; Stage III pancreatic adenocarcinoma
- Tags: subtype-page; gastrointestinal
- Group: gastrointestinal
- Burden: About a third of pancreatic cancers are found when the tumour has grown around the major arteries or blocked the main vein without spreading elsewhere; it is the stage where local treatments other than surgery have been tested hardest.
- Subtypes: Locally advanced PDAC with arterial encasement (superior mesenteric or coeliac artery); Locally advanced PDAC with unreconstructable venous occlusion; Locally advanced PDAC converted to resection after induction chemotherapy; Locally advanced PDAC progressing locally without metastases (ablative radiotherapy candidates); Locally advanced PDAC in patients unfit for combination chemotherapy (gemcitabine alone or chemoradiation)
- Biomarkers: Pancreas-protocol CT with arterial encasement (defines the stage); CA 19-9 at baseline and during induction (normalisation predicts a useful operation); Restaging CT and PET-CT after induction (occult metastases in a share of patients); Germline BRCA1, BRCA2 and PALB2 status (platinum choice); KRAS and other somatic alterations by tissue or plasma sequencing (trial eligibility); Nutritional status, pancreatic exocrine function and glycaemic control

## Standard of care

- Induction chemotherapy: Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside. ([FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [Biliary stenting and drainage](https://onco.cc/technologies/biliary-stenting-drainage/), [Cancer cachexia](https://onco.cc/terms/cachexia/))
- Tumour treating fields: Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026. ([Tumour treating fields (TTFields)](https://onco.cc/technologies/ttfields/), [Optune / Optune Pax (TTFields)](https://onco.cc/drugs/optune/), [PANOVA-3](https://onco.cc/trials/panova-3/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/))
- Consolidation local therapy: Chemoradiation with capecitabine, stereotactic body radiotherapy or MR-guided ablative radiotherapy after induction chemotherapy for disease that has not spread; LAP07 shows better local control without longer survival. ([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/), [Hypofractionated radiotherapy](https://onco.cc/technologies/hypofractionated-radiotherapy/))
- Conversion surgery: Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction. ([Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/), [Resectable, borderline resectable and unresectable](https://onco.cc/terms/resectability/), [CA 19-9](https://onco.cc/terms/ca19-9/), [Resection margins (R0 / R1 / R2)](https://onco.cc/terms/resection-margins/))
- Ablation: Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence. ([Irreversible electroporation (NanoKnife)](https://onco.cc/technologies/irreversible-electroporation/))
- Progression: Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials. ([NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)](https://onco.cc/drugs/nalirifox/), [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/), [RASolute 302](https://onco.cc/trials/rasolute-302/))

## State of the art

- Induction chemotherapy with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel is standard, with local therapy chosen afterwards by response.
- PANOVA-3 made tumour treating fields the first approved addition to chemotherapy in this stage.
- Ablative radiotherapy on MR-guided linear accelerators aims to control tumours that will never be removed.
- Conversion to surgery after induction is the aim, achieved in a minority.

## Open problems

- No local therapy after chemotherapy has lengthened survival in a randomised trial apart from tumour treating fields.
- Conversion surgery is uncommon and its benefit over continued non-surgical treatment is unproven.
- CT cannot distinguish fibrosis from living tumour after induction, so restaging is unreliable.
- Cachexia, pain and biliary complications limit how much treatment patients can receive.

## 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: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-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/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [FAPI PET](https://onco.cc/technologies/fapi-pet/), [Hypofractionated radiotherapy](https://onco.cc/technologies/hypofractionated-radiotherapy/), [Irreversible electroporation (NanoKnife)](https://onco.cc/technologies/irreversible-electroporation/), [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/), [MR-guided adaptive radiotherapy](https://onco.cc/technologies/mr-linac/), [PET/CT](https://onco.cc/technologies/pet-ct/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Tumour treating fields (TTFields)](https://onco.cc/technologies/ttfields/)
- targets: [FAP](https://onco.cc/targets/fap/), [KRAS](https://onco.cc/targets/kras/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [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/), [Optune / Optune Pax (TTFields)](https://onco.cc/drugs/optune/), [Zoldonrasib](https://onco.cc/drugs/zoldonrasib/)
- companies: [Novocure](https://onco.cc/companies/novocure/), [Revolution Medicines](https://onco.cc/companies/revolution-medicines/)
- pathways: [Cancer cachexia](https://onco.cc/pathways/cachexia-biology/), [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/), [Cancer cachexia](https://onco.cc/terms/cachexia/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/), [Locally advanced and locoregional disease](https://onco.cc/terms/locally-advanced/), [Obstructive jaundice and biliary obstruction](https://onco.cc/terms/obstructive-jaundice/), [Resectable, borderline resectable and unresectable](https://onco.cc/terms/resectability/), [Resection margins (R0 / R1 / R2)](https://onco.cc/terms/resection-margins/), [Stenting (biliary, oesophageal, airway)](https://onco.cc/terms/biliary-stent/), [Stereotactic body radiotherapy (SBRT / SABR)](https://onco.cc/terms/sbrt-term/), [Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/)
- trials: [A Phase 1 Study to Evaluate Safety and Efficacy of XER-001 (Amifostine for Nasoduodenal Delivery) in Combination With Sterotactic Body Radiotherapy for Treatment in Patients With Locally Advanced Pancreatic Cancer.](https://onco.cc/trials/nct07157033/), [Acoustic Cluster Therapy (ACT) With Chemotherapy for the Treatment of Locally Advanced Pancreatic Cancer](https://onco.cc/trials/nct06850623/), [Clinical Study of Tumor Treating Fields Combined with Gemcitabine and Albumin-bound Paclitaxel in the First-line Treatment of Locally Advanced Pancreatic Cancer](https://onco.cc/trials/nct05653453/), [Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer](https://onco.cc/trials/nct04390399/), [FOLFIRINOX Versus OncoSil™ in Addition to FOLFIRINOX in Patients With Locally Advanced Pancreatic Adenocarcinoma](https://onco.cc/trials/nct05466799/), [PANOVA-3](https://onco.cc/trials/panova-3/), [RASolute 302](https://onco.cc/trials/rasolute-302/)
- people: [Albert C. Koong](https://onco.cc/people/albert-koong/), [Eileen M. O'Reilly](https://onco.cc/people/eileen-oreilly/), [Hedy L. Kindler](https://onco.cc/people/hedy-kindler/), [Theodore S. Hong](https://onco.cc/people/theodore-hong/), [Theodore S. Lawrence](https://onco.cc/people/theodore-lawrence/), [Tobias Janowitz](https://onco.cc/people/tobias-janowitz/)
- 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/), [MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer](https://onco.cc/key-papers/paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013/)
- ideas: [Coverage-with-evidence registries for MR-guided and adaptive radiotherapy](https://onco.cc/ideas/idea-fund-adaptive-radiotherapy-evidence/), [Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3](https://onco.cc/ideas/idea-reg-losartan-pancreatic-stroma/)

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