Locally advanced unresectable pancreatic ductal adenocarcinoma
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
See all on the product pages:CapecitabineDaraxonrasibFOLFIRINOX / mFOLFIRINOXGemcitabine + nab-paclitaxelNALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)·Printable cards in the navigator
Anatomy and lymph node drainage
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- Nodes: peripancreatic
- Nodes: hepatic hilar
- Nodes: coeliac and superior mesenteric
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
- Pancreatic head (most PDAC)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)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- peripancreatic
- hepatic hilar
- coeliac and superior mesenteric
Same organ: Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma (perihilar and distal), Biliary tract cancer (all types), Neuroendocrine tumours, Pancreatic neuroendocrine tumours, Grade 3 well-differentiated neuroendocrine tumour, Extrapulmonary neuroendocrine carcinoma, Gallbladder cancer, Ampullary cancer (ampulla of Vater), Resectable pancreatic ductal adenocarcinoma, Borderline resectable pancreatic ductal adenocarcinoma, Metastatic pancreatic ductal adenocarcinoma, KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS wild-type pancreatic ductal adenocarcinoma, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Pancreatic acinar cell carcinoma, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Pancreatoblastoma
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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside.
Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026.
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.
Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction.
Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence.
Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials.
Subtypes & biomarkers
top- 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)
- 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
How often this target appears
- 1981Gastrointestinal Tumor Study Group: fluorouracil chemoradiation lengthens survival over radiotherapy alone in locally advanced disease
- 2011FOLFIRINOX result in metastatic disease is adopted as induction for locally advanced tumours
- 2016LAP07: chemoradiation after induction gemcitabine controls local growth but does not lengthen survival
- 2019Ablative MR-guided radiotherapy for locally advanced disease enters trials
- 2025PANOVA-3: tumour treating fields with gemcitabine plus nab-paclitaxel lengthen survival
- 2026Tumour treating fields device approved for locally advanced pancreatic cancer
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 11 changes by month →- 2026-09-18This recordLocally advanced unresectable pancreatic ductal adenocarcinomaFacts on this page last checked
When this page itself was last checked or edited.
- 2026-Q1RegulatoryOptune / Optune Pax (TTFields)Optune / Optune Pax (TTFields): approval (US)
Optune Pax, locally advanced pancreatic cancer with chemotherapy (PANOVA-3)
- 2026ApprovalOptune / Optune Pax (TTFields)Optune / Optune Pax (TTFields) approved in US
Locally advanced pancreatic cancer with chemotherapy
- 2026Trial resultRASolute 302RASolute 302 reported
OS 13.
- 2026MilestoneOptune / Optune Pax (TTFields)Tumour treating fields device approved for locally advanced pancreatic cancer
A milestone in how this cancer is treated.
- 2025Trial resultPANOVA-3PANOVA-3 reported
OS 16.
What is in development for Locally advanced unresectable pancreatic ductal adenocarcinoma, drawn from the whole corpus: 10 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 2 · 1
Technologies being tested · 1
Trials under way · 5
- Clinical Study of Tumor Treating Fields Combined with Gemcitabine and Albumin-bound Paclitaxel in the First-line Treatment of Locally Advanced Pancreatic Cancer · phase 3 · Jiangsu Healthy Life Innovation Medical Technology Co., Ltd
- FOLFIRINOX Versus OncoSil™ in Addition to FOLFIRINOX in Patients With Locally Advanced Pancreatic Adenocarcinoma · phase 2 · OncoSil Medical Limited
- Acoustic Cluster Therapy (ACT) With Chemotherapy for the Treatment of Locally Advanced Pancreatic Cancer · phase 2 · EXACT Therapeutics AS
- 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. · phase 1/2 · Xerient Pharma
- Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer · phase 2 · ImmunityBio, Inc.
Trials reported · 1
- PANOVA-3 · phase 3 · 2025 · positive
Ideas not yet in a trial · 2
Open problems and what is being done
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Houston · cancer center | United States | 0 | 6,724 | 95,007 | #2 | ||
London · cancer center | United Kingdom | none recorded | 0 | 1,026 | 17,745 | #7 | |
Boston · cancer center | United States | 1 | 4,335 | 73,845 | none recorded | #15 | |
Boston · hospital | United States | 0 | 3,582 | 54,857 | #16 | ||
Heidelberg · cancer center | Germany | none recorded | 0 | 3,456 | 45,745 | #18 | |
Manchester · cancer center | United Kingdom | none recorded | 0 | 104 | 2,145 | #23 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
Amsterdam · cancer center | Netherlands | none recorded | 0 | 1,451 | 25,873 | #45 | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Amsterdam · hospital | Netherlands | none recorded | 0 | 2,104 | 25,115 | - | |
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
St. Louis, MO · cancer center | United States | 0 | 1,950 | 25,697 | - | ||
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Locally advanced unresectable pancreatic ductal adenocarcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Locally advanced unresectable pancreatic ductal adenocarcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Pancreas-protocol CT with arterial encasement, CA 19-9 at baseline and during induction, Restaging CT and PET-CT after induction, Germline BRCA1, BRCA2 and PALB2 status, KRAS and other somatic alterations by tissue or plasma sequencing), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Locally advanced PDAC with arterial encasement, Locally advanced PDAC with unreconstructable venous occlusion, Locally advanced PDAC converted to resection after induction chemotherapy.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Induction chemotherapy
- For my situation (induction chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside.
- Am I a candidate for FOLFIRINOX / mFOLFIRINOX, Gemcitabine + nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Tumour treating fields
- For my situation (tumour treating fields), which of the standard options do you recommend and why?Why: Guideline options include: Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026.
- Am I a candidate for Optune / Optune Pax (TTFields), Gemcitabine + nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PANOVA-3 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Consolidation local therapy
- For my situation (consolidation local therapy), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Capecitabine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Conversion surgery
- For my situation (conversion surgery), which of the standard options do you recommend and why?Why: Guideline options include: Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction.
Ablation
- For my situation (ablation), which of the standard options do you recommend and why?Why: Guideline options include: Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence.
Progression
- For my situation (progression), which of the standard options do you recommend and why?Why: Guideline options include: Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials.
- Am I a candidate for NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Daraxonrasib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RASolute 302 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Clinical Study of Tumor Treating Fields Combined with Gemcitabine and Albumin-bound Paclitaxel in the First-line Treatment of Locally Advanced Pancreatic Cancer, FOLFIRINOX Versus OncoSil™ in Addition to FOLFIRINOX in Patients With Locally Advanced Pancreatic Adenocarcinoma, Acoustic Cluster Therapy (ACT) With Chemotherapy for the Treatment of Locally Advanced Pancreatic Cancer, 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.?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No local therapy after chemotherapy has lengthened survival in a randomised trial apart from tumour treating fields”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Conversion surgery is uncommon and its benefit over continued non-surgical treatment is unproven”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Locally advanced unresectable pancreatic ductal adenocarcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
13targets
2drugs
9companies
6pathways
3terms
11trials
7ideas
2people
6key papers
2With FOLFIRINOX this trial defined the two chemotherapy standards for metastatic pancreatic cancer that still apply, and the gemcitabine and nab-paclitaxel backbone is the comparator in most current first-line pancreatic trials.
FOLFIRINOX and, soon after, gemcitabine plus nab-paclitaxel ended the era of single-agent gemcitabine for metastatic pancreatic cancer. The regimen's modified form later improved survival after surgery in PRODIGE 24, and its toxicity is why fitness, not just stage, decides which treatment a patient is offered.
Latest papers
topQuery for this cancer: (TITLE:"Locally advanced unresectable pancreatic ductal adenocarcinoma" OR ABSTRACT:"Locally advanced unresectable pancreatic ductal adenocarcinoma" OR TITLE:"Locally advanced pancreatic cancer" OR ABSTRACT:"Locally advanced pancreatic cancer" OR TITLE:"LAPC" OR ABSTRACT:"LAPC" OR TITLE:"Unresectable non-metastatic pancreatic cancer" OR ABSTRACT:"Unresectable non-metastatic pancreatic cancer" OR TITLE:"Stage III pancreatic adenocarcinoma" OR ABSTRACT:"Stage III pancreatic adenocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Locally advanced unresectable pancreatic ductal adenocarcinoma, not a curated reading list.
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