Treating itPancreatic ductal adenocarcinoma

Annual MRI/MRCP or EUS for germline carriers and familial kindreds (CAPS/PRECEDE); germline testing for every diagnosed patient and first-degree relatives.

Neoadjuvant mFOLFIRINOX (borderline; increasingly resectable), surgery, then adjuvant mFOLFIRINOX to complete ~6 months (PRODIGE 24); gemcitabine/capecitabine if unfit. Chemoradiation selectively (PREOPANC).

FOLFIRINOX or gem/nab-paclitaxel; TTFields with gem/nab-paclitaxel (Optune Pax, 2026); SBRT or MR-guided ablative radiotherapy; IRE in selected centres; reassess for conversion surgery.

mFOLFIRINOX or NALIRIFOX (fit) or gemcitabine/nab-paclitaxel; olaparib maintenance if gBRCA after ≥16 weeks platinum; zenocutuzumab if NRG1 fusion; pembrolizumab if MSI-H; trials of RAS inhibitors + chemotherapy.

Daraxonrasib once approved (RASolute 302: OS 13.2 vs 6.7 months) is expected to become the standard; otherwise switch backbone (gem/nab-pac after FOLFIRINOX, or liposomal irinotecan/5-FU after gemcitabine).

Pancreatic protocol CT of chest, abdomen and pelvis before any biliary drainage; FDG PET-CT for localised disease before treatment; EUS with tissue sampling when a diagnosis or node staging is needed; MRI for suspected liver metastases and laparoscopy with laparoscopic ultrasound before an attempted resection when small-volume spread is suspected; CA 19-9 at baseline; germline testing for every patient; decision by a specialist pancreatic multidisciplinary team.

Enteric-coated pancreatin for everyone with unresectable disease and consideration before and after resection; early enteral rather than parenteral nutrition after pancreatoduodenectomy; no fish oils for weight loss in unresectable disease; dietitian assessment for the weight loss, malabsorption and cachexia that affect most patients.

About one in five pancreatic cancers can be removed at diagnosis (the OnCo record; Pancreatic Cancer UK says only a small number of people can have surgery), and the word the multidisciplinary team gives you decides the order. Resectable (no contact with the main arteries, no more than abutment of the veins, no spread): NICE NG85 says surgery first, and only consider chemotherapy before surgery within a clinical trial; the operation is usually a Whipple procedure for the head of the pancreas or a distal pancreatectomy for the body and tail, followed by six months of chemotherapy. Borderline resectable (the tumour touches a main vein or artery, so an operation straight away would probably leave cancer behind): chemotherapy first for two to four months, usually modified FOLFIRINOX, then restaging, with surgery about 6 to 8 weeks after chemotherapy if the disease has not spread; NICE NG85 also places this within a trial, and Cancer Research UK says your doctor may offer one because the best treatment is uncertain. In the Dutch PREOPANC trial, chemoradiotherapy before surgery improved five-year survival over surgery first (20.5% against 6.5%), most clearly for borderline disease; the record's open problems note the question is unresolved for resectable disease after PREOPANC-2, NORPACT-1 and Alliance A021806. Fitness matters as much as anatomy: only people well enough for a major operation are offered one, prehabilitation (exercise, nutrition, stopping smoking) is offered in some hospitals, and if jaundice needs relieving first a metal stent is placed. A second opinion from a specialist pancreatic centre is reasonable when the scan is read differently by different teams.

Three combinations are used for cancer that cannot be removed, chosen by how well you are (performance status), your liver tests, any nerve damage and what you prefer. FOLFIRINOX (fluorouracil, folinic acid, irinotecan and oxaliplatin, every two weeks with a 46-hour pump): NICE NG85 offers it to people with metastatic disease and a performance status of 0 to 1; in the 2011 trial median survival was 11.1 months against 6.8 with gemcitabine, with more diarrhoea, neuropathy and low blood counts, so most UK units give the modified doses. Gemcitabine with nab-paclitaxel (weekly drips for three weeks in four): improved survival over gemcitabine alone in MPACT (8.5 against 6.7 months) and causes hair loss, neuropathy and low counts; NICE TA476 funds it on the NHS only when other combinations are unsuitable and gemcitabine alone would otherwise be given. NALIRIFOX (liposomal irinotecan, oxaliplatin, fluorouracil): in NAPOLI 3 median survival was 11.1 months against 9.2 with gemcitabine and nab-paclitaxel; it is on the OnCo record beside modified FOLFIRINOX for fit patients but NHS funding follows NICE appraisals, so ask what applies where you are treated. Gemcitabine alone, or GemCap, for people not well enough for these; best supportive care when chemotherapy would do harm. Everyone has a DPD blood test before fluorouracil or capecitabine, blood counts before each dose, scans about every three months, and the same temperature rule for the 24-hour line. Second line follows NICE NG85: an oxaliplatin-based regimen if you have not had oxaliplatin, a gemcitabine-based one after FOLFIRINOX; liposomal irinotecan with fluorouracil after gemcitabine is not NICE-recommended (TA440). Daraxonrasib after first-line chemotherapy is on the record's second-line row.

Chemotherapy after the operation is what turns surgery into a real chance of cure. NICE NG85 says start once you have had time to recover and as soon as you are well enough to tolerate all six cycles, offers gemcitabine plus capecitabine (GemCap, from ESPAC-4: median survival 28.0 months against 25.5 with gemcitabine alone) and considers gemcitabine alone for those not well enough for a combination; since PRODIGE 24 (2018), modified FOLFIRINOX has become the standard for fit patients, with a median survival of 54.4 months against 35.0 with gemcitabine, at the cost of more diarrhoea, neuropathy and tiredness, and Pancreatic Cancer UK lists all three as the options, chosen by how well you are. Cancer Research UK and Pancreatic Cancer UK say it should start within 12 weeks (3 months) of surgery and lasts up to 6 months, so sorting out eating, weight, enzyme doses and blood sugar in the weeks after the operation matters: they are the usual reasons for a delay. Ask what the pathology showed about the resection margin (R0 or R1) and the lymph nodes. Follow-up after chemotherapy is usually a CT scan every 6 months for 5 years with blood tests and sometimes CA 19-9; contact the team about any new symptom between visits.

About one in ten pancreatic cancers runs in families (Pancreatic Cancer UK), and the OnCo record asks for a germline panel (BRCA1, BRCA2, PALB2, ATM, CDKN2A, STK11 and the Lynch genes) for everyone diagnosed. Three things follow from a BRCA1 or BRCA2 (or PALB2) result. Treatment: platinum chemotherapy (FOLFIRINOX or NALIRIFOX, which contain oxaliplatin) is favoured, and in the POLO trial maintenance olaparib after at least 16 weeks of platinum without progression lengthened the time before the cancer grew (7.4 against 3.8 months) without lengthening survival overall; NICE could not make a recommendation on olaparib in pancreatic cancer (TA750, terminated December 2021) because the company made no submission, so ask what is funded where you are treated. Family: Macmillan says each child of a carrier has a 1 in 2 chance of inheriting the variant; the genetics team can offer relatives predictive testing, and NICE NG85 says offer pancreatic surveillance (MRI/MRCP or EUS) to people with BRCA1, BRCA2, PALB2 or CDKN2A variants who have a first-degree relative with pancreatic cancer, and to those with Peutz-Jeghers syndrome or hereditary pancreatitis. Time: results usually take weeks to a few months; a variant of uncertain significance means the effect on risk is not yet known and the genetics team will explain it. Tumour testing (KRAS subtype, NRG1 and other fusions, mismatch repair) is separate and decides trial eligibility and the rare targeted drugs on the record.

Jaundice (yellow eyes or skin, dark urine, pale stools, itch) means the tumour is blocking the bile duct, and how it is relieved depends on the plan for the cancer. NICE NG85 says: if the cancer is resectable and you are well enough, offer the operation rather than draining the duct first (unless a trial requires drainage); if you are not yet fit for surgery, or will have chemotherapy first, offer a self-expanding metal stent placed by endoscopy (ERCP), a fully covered one where it may need removing later; if the cancer cannot be removed, offer a metal stent rather than a surgical bypass; and consider a surgical bypass (and a prophylactic gastrojejunostomy) only when the cancer turns out to be unresectable during an attempted resection. Pancreatic Cancer UK says most people feel better within a couple of days of a stent, the jaundice takes two to three weeks to clear completely, and that relieving it may be what allows chemotherapy to start; the problems are blockage (symptoms return), infection (antibiotics), the stent moving, and pancreatitis from the procedure. If ERCP fails the stent is placed through the skin (PTC). Macmillan says plastic stents may need replacing and metal ones usually do not. A blocked duodenum (vomiting large amounts, feeling full) is treated with a duodenal stent, or a gastrojejunostomy for people expected to live longer.

Many people with pancreatic cancer have pain in the upper tummy or back, often because the tumour presses on the coeliac plexus, the bundle of nerves behind the pancreas; Pancreatic Cancer UK says asking for help early makes it easier to control. The steps Cancer Research UK describes: paracetamol and anti-inflammatories, then weak and strong opioids (morphine-based medicines as tablets, liquids, patches or injections) with regular laxatives because opioids constipate, and anti-sickness medicine for the first week; amitriptyline or gabapentin for burning, tingling or shooting nerve pain; radiotherapy or chemotherapy to shrink what is pressing on the nerves, which takes weeks to work; and relaxation, TENS, acupuncture and distraction alongside. NICE NG85 says consider an EUS-guided or image-guided coeliac plexus block for uncontrolled pain, unacceptable opioid side effects or escalating doses, and not to offer thoracic splanchnicectomy; Macmillan describes the injection through the back or from inside the stomach during an endoscopic ultrasound, and a randomised trial (Wyse 2011) found early EUS-guided neurolysis reduced pain at three months. Pain after a Whipple operation is normal for weeks and eases; sudden worse pain with a temperature means A&E. Palliative care and pain teams can be involved at any stage, alongside treatment.

The pancreas digests food and controls blood sugar, and the cancer, the operation or both can take away either job. Enzymes: Pancreatic Cancer UK says most people with pancreatic cancer will need pancreatic enzyme replacement therapy (PERT: Creon, Nutrizym, Pancrex) for life, and that the signs of needing it are weight loss, bloating, wind, tummy pain after eating and pale, oily, floating stools. NICE NG85 says offer enteric-coated pancreatin in unresectable disease and consider it before and after resection. How to take it: with all meals, snacks and milky drinks, half with the first mouthfuls and half spread through the meal, swallowed with a cool drink, starting at about 50,000 to 75,000 units for a main meal and 25,000 to 50,000 for a snack, more for larger or fattier meals, reviewed by the dietitian and increased until symptoms settle; if it is not working, a proton pump inhibitor, another brand, or another cause (bile acid diarrhoea, bacterial overgrowth, medicines) is looked for. Supplies have been disrupted since 2024; NICE points prescribers to the Specialist Pharmacy Service tool for equivalents. Diabetes: pancreatic cancer or surgery can cause type 3c diabetes, which differs from type 1 and 2, usually needs tablets or insulin, and is managed by a diabetes nurse and specialist dietitian who know you have pancreatic cancer; a systematic review found new diabetes in about 16 in 100 people after a Whipple operation, and removing the whole pancreas means insulin for life. If you take insulin, tell the DVLA before driving. Ask both questions at the first appointment: they are the most fixable causes of feeling terrible.

Most people with pancreatic cancer lose appetite and weight (Cancer Research UK), and the loss has two parts: undigested food, which enzymes fix, and the cancer's own effect on appetite and muscle (cachexia), which needs a dietitian early. Cancer Research UK says most pancreatic teams include a dietitian, and its advice is small frequent meals, high-calorie and high-protein snacks and full-fat versions, prescribed supplement drinks sipped through the day (with enzymes, and checked against diabetes), and eating what you feel like rather than what you think you should. Pancreatic Cancer UK says there is no special diet and no foods to avoid, and not to cut fat but to take more PERT with it. Medicines for appetite: Macmillan says steroids or an appetite stimulant may help for a time; the ASCO cachexia guideline recommends dietary counselling and says no drug is established. NICE NG85 says do not offer fish oils to manage weight loss in unresectable disease, and after a Whipple operation to offer early feeding by mouth or tube rather than into a vein when the gut works. With a duodenal stent: soft, moist, lower-fibre foods, little and often, chewed well, upright after eating. Weight and muscle are also what decide whether chemotherapy can be given on time and in full, so ask for the referral in the first weeks, not when the weight has gone.

At every stage a trial can be a reasonable choice beside standard treatment, and in pancreatic cancer it is where the next answers are coming from: NICE NG85 itself places chemotherapy before surgery for resectable or borderline disease within trials, Cancer Research UK says your doctor may offer a trial for borderline disease because the best treatment is uncertain, and the record's pipeline is led by RAS inhibitors (daraxonrasib after first-line chemotherapy in RASolute 302, G12D-selective drugs, vaccines) that Pancreatic Cancer UK describes as a promising group of treatments. Ask what the comparison arm is, whether a placebo is used (the NHS says only where no proven treatment exists), whether a biopsy or tumour gene test is needed to qualify and whether tissue already taken can be used, what extra visits, scans and travel are involved and whether costs are paid, and what happens to your standard treatment if you leave; the NHS says you can leave at any time without giving a reason and without it affecting your care. Pancreatic Cancer UK has a trial finder and its nurses can talk through what a trial would mean for you.

Palliative care is symptom control and support, not a stage; Pancreatic Cancer UK says these services are not just for the end of life and are available at any point for cancer that cannot be cured, and a randomised trial (Temel 2010) found early palliative care alongside cancer treatment improved quality of life and mood. In pancreatic cancer the reasons to involve the team early are concrete: pain that may need a nerve block, sickness from a slow or blocked stomach, itch from jaundice, poor appetite and weight loss, fatigue, low mood, sleep, and the practical side (a written plan with numbers to ring at night, help at home, district nurses, a hospice's day services, money and work). The NHS says people whose cancer cannot be cured are referred to the palliative care or symptom control team, which works with you, your GP and the clinical nurse specialist, and that this team can help your loved ones too. NICE NG85 asks teams to assess the psychological impact of fatigue, pain, gut symptoms, nutrition, anxiety and depression throughout care. It is also the place to talk about what matters most to you and to record your wishes (advance care planning) while you are well enough to do it in your own words; Pancreatic Cancer UK's end of life pages, Marie Curie and Maggie's cover the conversations, and Pancreatic Cancer UK's nurses can be reached by phone, email or WhatsApp.

Upfront pancreatoduodenectomy or distal pancreatectomy followed by six months of adjuvant chemotherapy remains the reference for clearly resectable tumours: NORPACT-1 found 18-month survival 60 percent with neoadjuvant FOLFIRINOX against 73 percent with surgery first, SWOG S1505 found two-year survival of 47 to 48 percent with either perioperative regimen (no better than adjuvant history), and NEONAX missed its 18-month disease-free target in both arms. In favour of treating first: PREOPANC-1's neoadjuvant gemcitabine chemoradiotherapy gave five-year survival 20.5 against 6.5 percent (hazard ratio 0.73) across resectable and borderline patients, and PREOPANC-2 found neoadjuvant FOLFIRINOX and neoadjuvant chemoradiotherapy equivalent (21.9 against 21.3 months). Alliance A021806 (358 patients, perioperative against adjuvant modified FOLFIRINOX, primary completion December 2028) and PREOPANC-3 (378 patients) will settle the question; NICE NG85 restricts neoadjuvant therapy to trials (1.8.1, 1.8.2).

Modified FOLFIRINOX for six months in fit patients (PRODIGE 24: median overall survival 53.5 against 35.5 months with gemcitabine, hazard ratio 0.68, five-year survival 43.2 against 31.4 percent). Gemcitabine plus capecitabine for those not eligible (ESPAC-4: 28.0 against 25.5 months, hazard ratio 0.82; long-term 31.6 against 28.4 months, and 49.9 against 32.2 months after R0 resection); this is the NICE NG85 recommendation for England (1.8.6, off-label). Gemcitabine alone for the frail (CONKO-001: five-year survival 20.7 against 10.4 percent with observation; NG85 1.8.7). S-1 for six months in Japan (JASPAC 01: five-year survival 44.1 against 24.4 percent with gemcitabine, hazard ratio 0.57), not licensed for this use in Europe. Nab-paclitaxel with gemcitabine missed its primary endpoint (APACT) and is not a standard. Start within 12 weeks of surgery once recovered.

Neoadjuvant chemotherapy for two to four months, then restaging and surgery: ESPAC-5 (90 patients, UK and Germany) found one-year survival 39 percent with immediate surgery against 78 percent after gemcitabine plus capecitabine, 84 percent after FOLFIRINOX and 60 percent after chemoradiotherapy. Alliance A021501 established modified FOLFIRINOX alone as the reference regimen (18-month survival 66.7 percent, median 29.8 months) after its stereotactic radiotherapy arm closed at interim analysis for fewer R0 resections (10 against 17 of the first 30). PREOPANC-1 and PREOPANC-2 included borderline patients with the same conclusions as above. NICE NG85 still asks for neoadjuvant therapy to be given within a trial (1.8.1).

Four to six months of modified FOLFIRINOX or gemcitabine plus nab-paclitaxel (NEOLAP: conversion to resection in 36 to 44 percent of randomised patients with either sequence, median survival 18.5 to 20.7 months). Chemoradiotherapy after induction improves local control but not survival: LAP07 (15.2 against 16.5 months; local progression 32 against 46 percent), CONKO-007 (R0 resection 25 against 18 percent overall, not significant; 69 against 50 percent among those operated; survival hazard ratio 0.94). When it is used, capecitabine is the radiosensitiser (SCALOP: median survival 15.2 against 13.4 months with gemcitabine; NG85 1.9.3). Stereotactic radiotherapy and irreversible electroporation are options in centres with experience: CROSSFIRE (68 patients after FOLFIRINOX) found MRI-guided stereotactic radiotherapy and electroporation equivalent (16.1 against 12.5 months, hazard ratio 1.39, stopped for futility), and PANFIRE-2 (50 patients) reported median survival 17 months from diagnosis with major complications in 42 percent. Tumour treating fields added to gemcitabine plus nab-paclitaxel are approved in the United States (PANOVA-3).

FOLFIRINOX for performance status 0 to 1 (PRODIGE 4/ACCORD 11: median overall survival 11.1 against 6.8 months with gemcitabine, hazard ratio 0.57; febrile neutropenia 5.4 percent) or NALIRIFOX (NAPOLI 3: 11.1 against 9.2 months with nab-paclitaxel and gemcitabine, hazard ratio 0.83; FDA approval 13 February 2024, EU indication listed, no NICE appraisal). Gemcitabine plus nab-paclitaxel for those less fit or with biliary stents (MPACT: 8.5 against 6.7 months, hazard ratio 0.72; grade 3 or worse neuropathy 17 percent); in England only when other combinations are unsuitable (NICE TA476). Gemcitabine alone for the frail. Four months of FOLFIRINOX then fluorouracil and leucovorin maintenance is an alternative to six months (PANOPTIMOX-PRODIGE 35: six-month progression-free survival 42.9 against 47.1 percent, survival without quality-of-life deterioration 11.4 against 7.2 months). Germline and tumour testing at diagnosis (BRCA, PALB2, mismatch repair, KRAS subtype, NRG1 and NTRK fusions) steers maintenance and later lines.

Daraxonrasib after one prior line (RASolute 302: median overall survival 13.2 against 6.7 months with chemotherapy, hazard ratio 0.40; progression-free 7.2 against 3.6 months; FDA approval 26 August 2026 for metastatic pancreatic adenocarcinoma after one systemic therapy or for people not fit for multi-agent chemotherapy; no EU or UK decision). Otherwise switch backbone: after gemcitabine, liposomal irinotecan with fluorouracil and leucovorin (NAPOLI-1: 6.1 against 4.2 months, hazard ratio 0.67; FDA 2015, EU 2016, not recommended by NICE TA440) or OFF (CONKO-003: 5.9 against 3.3 months, hazard ratio 0.66), noting that PANCREOX found modified FOLFOX6 worse than fluorouracil alone; after FOLFIRINOX, gemcitabine plus nab-paclitaxel. NG85 recommends oxaliplatin-based or gemcitabine-based second line (1.9.7, 1.9.8). Pegilodecakin (SEQUOIA) and eryaspase (TRYbeCA-1) failed here.

Olaparib 300 mg twice daily for people with a germline BRCA1 or BRCA2 mutation whose metastatic disease has not progressed after at least 16 weeks of platinum chemotherapy (POLO: progression-free survival 7.4 against 3.8 months, hazard ratio 0.53; overall survival 19.0 against 19.2 months, hazard ratio 0.83, not significant; three-year survival 33.9 against 17.8 percent; FDA approval 2019, EU indication listed, no NICE appraisal). Continued chemotherapy, or fluorouracil and leucovorin maintenance after FOLFIRINOX (PANOPTIMOX), are the alternatives for everyone else. About 4 to 7 percent of patients carry a germline BRCA mutation; 3,315 were screened to randomise 154 in POLO.

RAS: daraxonrasib works across RAS G12 mutations (91.8 percent of RASolute 302) and is approved regardless of subtype; KRAS G12C (1 to 2 percent of tumours) responds to sotorasib (CodeBreaK 100 pancreatic cohort, 38 patients: response 21 percent, median survival 6.9 months) and adagrasib (KRYSTAL-1: 7 of 21 responses), which NCCN lists but no regulator has approved for pancreatic cancer; KRAS G12D (about 40 percent) has zoldonrasib in phase 3 first line (RASolute 305 with chemotherapy, RASolute 309 with daraxonrasib) after MRTX1133 was stopped. NRG1 fusions (KRAS wild-type tumours): zenocutuzumab (eNRGy: response 42 percent in 36 pancreatic patients; FDA accelerated approval 4 December 2024; not authorised in the EU). Mismatch repair deficiency (about 1 percent): pembrolizumab (KEYNOTE-158 pancreatic cohort: 4 of 22 responses, 18 percent) or dostarlimab under tumour-agnostic US approvals; NICE TA914 does not cover pancreatic cancer. NTRK fusions: larotrectinib (NICE TA630, Cancer Drugs Fund) or entrectinib (TA644 replaced by the terminated TA1118); repotrectinib after resistance. BRAF V600E: dabrafenib plus trametinib. Erlotinib with gemcitabine is licensed for metastatic disease in the US and EU but added under two weeks in its pivotal trial and nothing in later trials, and is not used.

Alternating electric fields at 150 kHz worn for at least 18 hours a day through skin arrays, with gemcitabine plus nab-paclitaxel (PANOVA-3, 571 patients: median overall survival 16.2 against 14.2 months, hazard ratio 0.82; pain-free survival 15.2 against 9.1 months; progression-free survival, local control and response not improved; device-related skin events in 76.3 percent, grade 3 in 7.7 percent). FDA approval of Optune Pax in 2026; no NICE appraisal. Open-label design and the modest effect are debated, and the device is not yet part of European guidelines.

Personalised mRNA neoantigen vaccine: in the 16-patient phase 1, autogene cevumeran after surgery with atezolizumab and modified FOLFIRINOX induced T cells in 8, whose recurrence-free survival was not reached against 13.4 months in non-responders at 3.2 years, with vaccine-induced T cell clones estimated to live 7.7 years; the randomised phase 2 IMCODE003 (260 patients, eight UK sites) is closed to recruitment with disease-free survival due in 2031. Shared KRAS peptide vaccine ELI-002 7P missed its primary endpoint in AMPLIFY-7P (2026). GVAX with CRS-207 failed in ECLIPSE. Claudin 18.2 CAR-T (satricabtagene autoleucel) and mesothelin-directed cells are in early trials. Checkpoint inhibitors alone do not work outside mismatch repair deficient disease.

Added to chemotherapy without survival benefit in phase 3: pegvorhyaluronidase alfa (HALO-301), pegilodecakin (SEQUOIA), napabucasin (CanStem111P), ibrutinib (RESOLVE), devimistat (AVENGER 500), pamrevlumab (LAPIS), eryaspase (TRYbeCA-1), algenpantucel-L (IMPRESS), erlotinib as adjuvant (CONKO-005, RTOG 0848) and in locally advanced disease (LAP07). Chemoradiotherapy after induction improved local control or R0 rates but not survival (LAP07, CONKO-007), and adjuvant chemoradiotherapy was harmful in ESPAC-1. MRTX1133 (KRAS G12D) was terminated in 2025 and the ELI-002 7P vaccine missed in 2026. Neoadjuvant FOLFIRINOX for clearly resectable disease was not better than surgery first (NORPACT-1) or than chemoradiotherapy (PREOPANC-2), and adjuvant nab-paclitaxel with gemcitabine missed its primary endpoint (APACT).

Commissioned in England: FOLFIRINOX first line for performance status 0 to 1 and gemcitabine combinations or gemcitabine alone otherwise (NG85 1.9.4 to 1.9.6, several off-label); nab-paclitaxel with gemcitabine only when other combinations are unsuitable (TA476); adjuvant gemcitabine plus capecitabine or gemcitabine (NG85 1.8.6, 1.8.7); oxaliplatin-based or gemcitabine-based second line (1.9.7, 1.9.8); larotrectinib for NTRK fusions through the Cancer Drugs Fund (TA630). Not recommended: liposomal irinotecan with fluorouracil after gemcitabine (TA440). Ended: entrectinib (TA1118 terminated, January 2026). Not appraised: NALIRIFOX, olaparib for pancreatic cancer, daraxonrasib, zenocutuzumab, tumour treating fields, sotorasib and adagrasib for pancreatic cancer; pembrolizumab for mismatch repair deficient tumours (TA914) does not include pancreatic cancer. Neoadjuvant therapy is trial-only under NG85.

Self-expanding metal stent by ERCP for jaundice in unresectable disease and, when drainage is needed before surgery, in resectable disease (NG85 1.7.3 to 1.7.5); metal stents stay open 4.45 months longer than plastic with fewer cholangitis episodes and re-interventions (Almadi 2017, 20 trials). Endoscopic ultrasound-guided drainage when ERCP fails or is expected to be difficult (Paik 2018; DRA-MBO 2023). Surgery first rather than preoperative drainage in fit resectable patients (1.7.1). For duodenal obstruction, an enteral stent relieves symptoms within days and gastrojejunostomy lasts longer (SUSTENT); choose bypass for people with a better prognosis (1.7.8) and consider prophylactic gastrojejunostomy when a tumour is found unresectable at operation (1.7.6).

Opioid analgesia with endoscopic ultrasound-guided or percutaneous coeliac plexus block for uncontrolled pain, opioid side effects or escalating doses (NG85 1.5.1; Wyse 2011 randomised trial: pain scores lower at three months, no survival effect); no thoracic splanchnicectomy (1.5.2). Enteric-coated pancreatin with every meal for everyone with unresectable disease and around surgery (1.6.1, 1.6.2); no fish oils for weight loss (1.6.3); early enteral rather than parenteral nutrition after pancreatoduodenectomy (1.6.4). Dietetic review and early palliative care from diagnosis. Cachexia drugs are in trials (ponsegromab, seven UK sites). Thromboprophylaxis is decided by risk score under the NICE venous thromboembolism guideline; in CASSINI's pancreatic subgroup rivaroxaban cut clots during treatment (3.7 against 10.1 percent) but not over 180 days.