{"entity":{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","aka":["Locally advanced pancreatic cancer","LAPC","Unresectable non-metastatic pancreatic cancer","Stage III pancreatic adenocarcinoma"],"tldr":"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.\n\nInduction 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.\n\nAfter 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 do not become resectable.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pancreatic_cancer"},{"label":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}],"tags":["subtype-page","gastrointestinal"],"related":["borderline-resectable-pdac","resectable-pdac","metastatic-pdac","kras-g12c-pdac","kras-wild-type-pdac","msi-high-pdac"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","ttfields","sbrt","mr-linac","hypofractionated-radiotherapy","irreversible-electroporation","biliary-stenting-drainage","kras-inhibitors","fapi-pet","pet-ct"],"targets":["kras","fap"],"drugs":["folfirinox","gemcitabine-nab-paclitaxel","gemcitabine","capecitabine","optune","daraxonrasib","zoldonrasib"],"companies":["novocure","revolution-medicines"],"institutions":[],"pathways":["pancreatic-cancer-signalling","caf-activation-desmoplasia","cachexia-biology"],"terms":["locally-advanced","resectability","chemoradiation","sbrt-term","ca19-9","obstructive-jaundice","biliary-stent","cachexia","desmoplasia"],"trials":["panova-3","nct05653453","nct05466799","nct06850623","nct07157033","nct04390399"],"people":["theodore-hong","albert-koong","theodore-lawrence","eileen-oreilly","tobias-janowitz","hedy-kindler"],"bottlenecks":[],"keyPapers":["paper-conroy-folfirinox-pancreatic-nejm-2011","paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013","paper-lap07-chemoradiotherapy-locally-advanced-pancreatic-jama-2016"],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"Induction chemotherapy","approach":"Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel for four to six months, with biliary stenting, pancreatic enzyme replacement and pain control alongside.","refs":["folfirinox","gemcitabine-nab-paclitaxel","biliary-stenting-drainage","cachexia"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Tumour treating fields","approach":"Alternating electric fields delivered through skin arrays added to gemcitabine plus nab-paclitaxel (PANOVA-3), approved in 2026.","refs":["ttfields","optune","panova-3","gemcitabine-nab-paclitaxel"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Consolidation local therapy","approach":"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.","refs":["chemoradiation","sbrt","mr-linac","capecitabine","hypofractionated-radiotherapy","lap07"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Conversion surgery","approach":"Exploration and resection, sometimes with arterial reconstruction, for the minority with stable or responding disease and a normalised CA 19-9 after induction.","refs":["whipple","resectability","ca19-9","resection-margins"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Ablation","approach":"Irreversible electroporation in selected centres after induction chemotherapy; no randomised evidence.","refs":["irreversible-electroporation"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Progression","approach":"Treat as metastatic disease: switch backbone, daraxonrasib after first-line chemotherapy, clinical trials.","refs":["nalirifox","daraxonrasib","rasolute-302"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}}],"stateOfArt":["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 do not become resectable after induction.","Conversion to surgery after induction is the aim, achieved in a minority."],"history":[{"year":1981,"title":"Gastrointestinal Tumor Study Group: fluorouracil chemoradiation lengthens survival over radiotherapy alone in locally advanced disease","refs":["fluorouracil","chemoradiation"]},{"year":2011,"title":"FOLFIRINOX result in metastatic disease is adopted as induction for locally advanced tumours","refs":["folfirinox","paper-conroy-folfirinox-pancreatic-nejm-2011"]},{"year":2016,"title":"LAP07: chemoradiation after induction gemcitabine controls local growth but does not lengthen survival","refs":["chemoradiation","gemcitabine"]},{"year":2019,"title":"Ablative MR-guided radiotherapy for locally advanced disease enters trials","refs":["mr-linac","sbrt"]},{"year":2025,"title":"PANOVA-3: tumour treating fields with gemcitabine plus nab-paclitaxel lengthen survival","refs":["panova-3","ttfields","gemcitabine-nab-paclitaxel"]},{"year":2026,"title":"Tumour treating fields device approved for locally advanced pancreatic cancer","refs":["optune","novocure"]}],"pipeline":["nct05653453","nct05466799","nct06850623","nct07157033","nct04390399","daraxonrasib","zoldonrasib","mr-linac","irreversible-electroporation","idea-reg-losartan-pancreatic-stroma","idea-fund-adaptive-radiotherapy-evidence"],"openProblems":["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."],"parent":"pancreatic"},"route":"/cancers/locally-advanced-pdac/","neighbours":{"cancer":[{"id":"borderline-resectable-pdac","kind":"cancer","name":"Borderline resectable pancreatic ductal adenocarcinoma","route":"/cancers/borderline-resectable-pdac/"},{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"biliary-stenting-drainage","kind":"technology","name":"Biliary stenting and drainage","route":"/technologies/biliary-stenting-drainage/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"fapi-pet","kind":"technology","name":"FAPI PET","route":"/technologies/fapi-pet/"},{"id":"hypofractionated-radiotherapy","kind":"technology","name":"Hypofractionated radiotherapy","route":"/technologies/hypofractionated-radiotherapy/"},{"id":"irreversible-electroporation","kind":"technology","name":"Irreversible electroporation (NanoKnife)","route":"/technologies/irreversible-electroporation/"},{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"},{"id":"mr-linac","kind":"technology","name":"MR-guided adaptive 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mFOLFIRINOX","route":"/drugs/folfirinox/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"gemcitabine-nab-paclitaxel","kind":"drug","name":"Gemcitabine + nab-paclitaxel","route":"/drugs/gemcitabine-nab-paclitaxel/"},{"id":"nalirifox","kind":"drug","name":"NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)","route":"/drugs/nalirifox/"},{"id":"optune","kind":"drug","name":"Optune / Optune Pax (TTFields)","route":"/drugs/optune/"},{"id":"pancrelipase","kind":"drug","name":"Pancrelipase (pancreatic enzyme replacement therapy)","route":"/drugs/pancrelipase/"},{"id":"zoldonrasib","kind":"drug","name":"Zoldonrasib","route":"/drugs/zoldonrasib/"}],"company":[{"id":"gercor","kind":"company","name":"GERCOR","route":"/companies/gercor/"},{"id":"novocure","kind":"company","name":"Novocure","route":"/companies/novocure/"},{"id":"revolution-medicines","kind":"company","name":"Revolution 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(biliary, oesophageal, airway)","route":"/terms/biliary-stent/"},{"id":"sbrt-term","kind":"term","name":"Stereotactic body radiotherapy (SBRT / SABR)","route":"/terms/sbrt-term/"},{"id":"vascular-resection-pancreatic","kind":"term","name":"Vascular resection in pancreatic cancer surgery (portal and superior mesenteric vein resection; arterial resection)","route":"/terms/vascular-resection-pancreatic/"},{"id":"whipple","kind":"term","name":"Whipple procedure (pancreaticoduodenectomy)","route":"/terms/whipple/"}],"trial":[{"id":"nct07333287","kind":"trial","name":"A Multicenter Single-arm Prospective Clinical Study on First-line Treatment of Pancreatic Cancer Liver Metastases With Arterial Infusion Chemotherapy and Emboli","route":"/trials/nct07333287/"},{"id":"nct07736612","kind":"trial","name":"A Pan-RAS Inhibitor in Combination With Anti-Tumor Therapy in Participants With Advanced Pancreatic Cancer","route":"/trials/nct07736612/"},{"id":"nct07157033","kind":"trial","name":"A Phase 1 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