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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.
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 do not become resectable.
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.
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.
Same organ: Glucagonoma, VIPoma, Somatostatinoma, 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, Gallbladder adenocarcinoma, Papillary carcinoma of the gallbladder, Mucinous carcinoma of the gallbladder, Adenosquamous and squamous carcinoma of the gallbladder, Neuroendocrine carcinoma of the gallbladder, Incidental gallbladder cancer (found after cholecystectomy), Carcinoma in situ and dysplasia of the gallbladder, Cystic duct carcinoma, 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, Adenosquamous carcinoma of the pancreas, Colloid (mucinous non-cystic) carcinoma of the pancreas, Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, Invasive carcinoma arising in an intraductal papillary mucinous neoplasm (IPMN-associated carcinoma), Mucinous cystic neoplasm of the pancreas with associated invasive carcinoma (MCN-associated carcinoma), Solid pseudopapillary neoplasm of the pancreas
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.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Answer a few questions from a report and read the guideline statement that applies, quoted word for word with its source. Educational aids to prepare for an appointment, not advice.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
The three main regimens share low blood counts, tiredness, sickness and sore mouth; FOLFIRINOX and NALIRIFOX add irinotecan diarrhoea and oxaliplatin's cold-triggered tingling and rare throat spasm, gemcitabine with nab-paclitaxel adds hair loss and neuropathy, and every regimen comes with the same temperature rule for ringing the 24-hour line.
The bowel cancer regimens share low blood counts, tiredness, sickness and a sore mouth. Oxaliplatin adds cold-triggered tingling, irinotecan adds early and late diarrhoea, capecitabine adds hand-foot syndrome and needs a DPD test first, and cetuximab or panitumumab add an acne-like rash and low magnesium. The rule for all of them: ring the 24-hour number rather than wait.
See all on the product pages:CapecitabineDaraxonrasibFOLFIRINOX / mFOLFIRINOXGemcitabine + nab-paclitaxelNALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)·Printable cards in the navigator
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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