{"entity":{"id":"borderline-resectable-pdac","kind":"cancer","name":"Borderline resectable pancreatic ductal adenocarcinoma","aka":["Borderline resectable pancreatic cancer","BRPC","Marginally resectable pancreatic cancer"],"tldr":"Borderline resectable pancreatic cancer touches the big blood vessels behind the pancreas, so an operation straight away would probably leave cancer behind. Chemotherapy first, usually FOLFIRINOX for several months and sometimes radiotherapy, shrinks the edge of the tumour, and patients whose disease has not spread go on to surgery with a better chance of a clean removal.","summary":"Borderline resectable disease is defined anatomically: tumour contact with the superior mesenteric or portal vein that is reconstructable, abutment of the superior mesenteric artery of 180 degrees or less, or limited contact with the hepatic artery. The MD Anderson, NCCN and international consensus definitions differ in detail and some add biological criteria, such as a very high CA 19-9 or suspicious regional nodes, and conditional criteria such as poor performance status. The point of the category is that upfront surgery leaves a positive margin in a large share of patients and that neoadjuvant treatment selects those who will benefit from a difficult operation.\n\nNeoadjuvant therapy is standard. PREOPANC-1 (2020, long-term follow-up 2022) randomised resectable and borderline patients to gemcitabine-based chemoradiation before surgery or upfront surgery and found more clear-margin resections and better long-term survival, with the benefit concentrated in the borderline group. PREOPANC-2 then compared neoadjuvant FOLFIRINOX with gemcitabine chemoradiation and found no difference, and ESPAC-5 found that neoadjuvant chemotherapy beat immediate surgery for borderline disease. Modified FOLFIRINOX for two to four months is the usual regimen, with gemcitabine plus nab-paclitaxel for less fit patients. The role of radiotherapy after chemotherapy is disputed: ALLIANCE A021501 (2022) stopped its stereotactic radiotherapy arm early because outcomes were worse than with chemotherapy alone, while other groups use conventional or ablative chemoradiation to secure the arterial margin.\n\nAfter neoadjuvant treatment patients are restaged with CT and CA 19-9; radiological shrinkage is often modest even when the tumour has responded, so surgeons operate on patients with stable disease, falling CA 19-9 and good fitness. Resection with venous reconstruction is routine in specialist centres and arterial resection is done selectively. Pathological response predicts survival, and patients complete a total of six months of chemotherapy after surgery where possible. Germline testing is offered to all, and a BRCA or PALB2 variant argues for a platinum-containing regimen. Trials are adding RAS inhibitors and vaccines to neoadjuvant chemotherapy and testing circulating tumour DNA to decide who should proceed to surgery.","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":["resectable-pdac","locally-advanced-pdac","metastatic-pdac","brca-palb2-pdac","kras-g12c-pdac"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","sbrt","mr-linac","robotic-surgery","ct","biliary-stenting-drainage","kras-inhibitors","pdac-organoid-pharmacotyping","liquid-biopsy"],"targets":["kras","brca"],"drugs":["folfirinox","gemcitabine-nab-paclitaxel","gemcitabine","capecitabine","daraxonrasib","autogene-cevumeran"],"companies":["revolution-medicines","biontech"],"institutions":[],"pathways":["pancreatic-cancer-signalling","caf-activation-desmoplasia"],"terms":["resectability","whipple","ca19-9","chemoradiation","sbrt-term","resection-margins","neoadjuvant-adjuvant","locally-advanced","ctdna"],"trials":["preopanc","prodige-24","nct07252232","nct02843945"],"people":["marc-besselink","theodore-hong","albert-koong","richard-schulick","jurgen-weitz","eileen-oreilly"],"bottlenecks":[],"keyPapers":["paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022","paper-espac-5-neoadjuvant-borderline-resectable-pancreatic-lancet-gastro-hep-2023","paper-alliance-a021501-mfolfirinox-radiotherapy-borderline-resectable-jama-oncol-2022","paper-conroy-folfirinox-pancreatic-nejm-2011"],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"A fifth or so of newly diagnosed pancreatic cancers touch a major vein or artery enough to make a clear-margin operation uncertain; how many are called borderline depends on the surgeon and the definition used.","subtypes":["Borderline resectable PDAC with venous involvement only (reconstructable portal or superior mesenteric vein)","Borderline resectable PDAC with limited arterial abutment (superior mesenteric or hepatic artery)","Biologically borderline PDAC (very high CA 19-9 or suspicious nodes with resectable anatomy)","Borderline resectable PDAC converted to resection after FOLFIRINOX","Borderline resectable PDAC that progresses during neoadjuvant therapy (treated as advanced disease)"],"biomarkers":["Pancreas-protocol CT with degrees of vessel contact (defines the category)","CA 19-9 trend during neoadjuvant chemotherapy (falling levels predict a useful operation)","Restaging CT after chemotherapy (stable disease is acceptable; shrinkage is often modest)","Germline BRCA1, BRCA2, PALB2 and ATM status (platinum choice)","Pathological response grade and margin status after resection","Circulating tumour DNA before surgery (investigational selection marker)"],"standardOfCare":[{"setting":"Neoadjuvant chemotherapy","approach":"Modified FOLFIRINOX for two to four months in fit patients, gemcitabine plus nab-paclitaxel otherwise; restage with CT and CA 19-9 before deciding on surgery (PREOPANC, ESPAC-5).","refs":["folfirinox","gemcitabine-nab-paclitaxel","preopanc","ca19-9","neoadjuvant-adjuvant","espac-5"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Radiotherapy after chemotherapy","approach":"Optional; conventional chemoradiation or stereotactic radiotherapy to secure an arterial margin in selected patients, with ALLIANCE A021501 as the caution against routine use.","refs":["chemoradiation","sbrt","mr-linac","capecitabine"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Surgery","approach":"Pancreatoduodenectomy or distal pancreatectomy with venous resection and reconstruction where needed, arterial resection only in specialist centres; proceed on stable or improved disease with falling CA 19-9.","refs":["whipple","resection-margins","resectability","robotic-surgery"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"After surgery","approach":"Complete six months of chemotherapy in total, usually with the regimen the tumour responded to.","refs":["folfirinox","gemcitabine-nab-paclitaxel","gemcitabine","capecitabine"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}},{"setting":"Progression during neoadjuvant therapy","approach":"Manage as locally advanced or metastatic disease; switch chemotherapy backbone, RAS inhibitor trials, biliary stenting for jaundice.","refs":["nalirifox","daraxonrasib","biliary-stenting-drainage"],"guideline":{"version":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}}],"stateOfArt":["Neoadjuvant chemotherapy is the standard for borderline disease, with modified FOLFIRINOX the usual regimen (PREOPANC, ESPAC-5).","Venous resection and reconstruction is routine in high-volume centres and no longer a reason to call a tumour unresectable.","The role of radiotherapy is being redefined after ALLIANCE A021501, with ablative and MR-guided techniques in trials.","RAS inhibitors and vaccines are entering neoadjuvant trials for the first time."],"history":[{"year":2006,"title":"MD Anderson defines borderline resectable disease by degrees of vessel contact","refs":["resectability"]},{"year":2011,"title":"FOLFIRINOX proves active in metastatic disease and is taken up as a neoadjuvant regimen","refs":["folfirinox","paper-conroy-folfirinox-pancreatic-nejm-2011"]},{"year":2020,"title":"PREOPANC-1: neoadjuvant chemoradiation improves clear-margin resection and long-term survival","refs":["preopanc","chemoradiation"]},{"year":2022,"title":"ALLIANCE A021501: adding stereotactic radiotherapy to neoadjuvant FOLFIRINOX gives worse outcomes","refs":["sbrt","folfirinox"]},{"year":2023,"title":"ESPAC-5: neoadjuvant chemotherapy beats immediate surgery for borderline disease","refs":["gemcitabine","capecitabine","folfirinox"]},{"year":2024,"title":"PREOPANC-2: neoadjuvant FOLFIRINOX and gemcitabine chemoradiation give similar survival","refs":["preopanc","folfirinox"]}],"pipeline":["nct07252232","nct02843945","daraxonrasib","autogene-cevumeran","idea-ras-inhibitor-neoadjuvant-pdac","mr-linac","pdac-organoid-pharmacotyping","idea-tr2-organoid-coclinical-arms"],"openProblems":["Definitions of borderline disease differ between centres, so trial populations are not comparable.","CT underestimates response after chemotherapy, and there is no validated marker to tell fibrosis from viable tumour before surgery.","Whether radiotherapy adds anything after modern chemotherapy is unresolved.","Arterial resection carries high morbidity and its benefit is unproven outside expert centres."],"parent":"pancreatic"},"route":"/cancers/borderline-resectable-pdac/","neighbours":{"cancer":[{"id":"brca-palb2-pdac","kind":"cancer","name":"BRCA or PALB2-mutant pancreatic ductal adenocarcinoma","route":"/cancers/brca-palb2-pdac/"},{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-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":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mr-linac","kind":"technology","name":"MR-guided adaptive radiotherapy","route":"/technologies/mr-linac/"},{"id":"pdac-organoid-pharmacotyping","kind":"technology","name":"PDAC organoid pharmacotyping","route":"/technologies/pdac-organoid-pharmacotyping/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"autogene-cevumeran","kind":"drug","name":"Autogene cevumeran","route":"/drugs/autogene-cevumeran/"},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"daraxonrasib","kind":"drug","name":"Daraxonrasib","route":"/drugs/daraxonrasib/"},{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / 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/"}],"company":[{"id":"biontech","kind":"company","name":"BioNTech","route":"/companies/biontech/"},{"id":"dpcg","kind":"company","name":"Dutch Pancreatic Cancer Group","route":"/companies/dpcg/"},{"id":"revolution-medicines","kind":"company","name":"Revolution Medicines","route":"/companies/revolution-medicines/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"}],"term":[{"id":"ca19-9","kind":"term","name":"CA 19-9","route":"/terms/ca19-9/"},{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"locally-advanced","kind":"term","name":"Locally advanced and locoregional disease","route":"/terms/locally-advanced/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"neoadjuvant-versus-upfront-surgery-pancreatic","kind":"term","name":"Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer","route":"/terms/neoadjuvant-versus-upfront-surgery-pancreatic/"},{"id":"pancreas-protocol-ct","kind":"term","name":"Pancreas protocol CT (pancreatic protocol CT, dual-phase thin-slice CT with structured reporting)","route":"/terms/pancreas-protocol-ct/"},{"id":"pancreatic-trials-open-today","kind":"term","name":"Pancreatic cancer trials open today (registry snapshot and UK sites)","route":"/terms/pancreatic-trials-open-today/"},{"id":"r0-r1-margin-pancreatic","kind":"term","name":"R0 and R1 margins in pancreatic cancer: the 1 mm rule and standardised specimen reporting","route":"/terms/r0-r1-margin-pancreatic/"},{"id":"nccn-resectability-criteria-pancreatic","kind":"term","name":"Resectability classes for pancreatic cancer (NCCN anatomical criteria and the 2017 international consensus)","route":"/terms/nccn-resectability-criteria-pancreatic/"},{"id":"resectability","kind":"term","name":"Resectable, borderline resectable and unresectable","route":"/terms/resectability/"},{"id":"resection-margins","kind":"term","name":"Resection margins (R0 / R1 / R2)","route":"/terms/resection-margins/"},{"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":"nct07043270","kind":"trial","name":"24BRO681 : Alternating Gnp and mFOLFIRINOX for BR-PDAC","route":"/trials/nct07043270/"},{"id":"nct06944106","kind":"trial","name":"A Study on Ivonescimab Plus Chemotherapy as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer","route":"/trials/nct06944106/"},{"id":"nct07208539","kind":"trial","name":"AG Followed by FOLFIRINOX Both Combined With PD-L1 Antibodies as a Conversion Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.","route":"/trials/nct07208539/"},{"id":"alliance-a021501","kind":"trial","name":"Alliance A021501","route":"/trials/alliance-a021501/"},{"id":"nct06483555","kind":"trial","name":"Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel","route":"/trials/nct06483555/"},{"id":"nct06690528","kind":"trial","name":"Conversion Surgery Vs. Palliative Care in Pancreatic Cancer Oligometastatic to the Liver","route":"/trials/nct06690528/"},{"id":"nct07705919","kind":"trial","name":"DCE-MRI for Neoadjuvant Treatment Assessment in Patients With Borderline Resectable Pancreatic Cancer","route":"/trials/nct07705919/"},{"id":"nct07698613","kind":"trial","name":"EGFR Targeted Photoimmunotherapy With ASP-1929 for Locally Advanced Pancreatic Cancer","route":"/trials/nct07698613/"},{"id":"espac-5","kind":"trial","name":"ESPAC-5","route":"/trials/espac-5/"},{"id":"nct06423326","kind":"trial","name":"Gemcitabine, Cisplatin and Nab-Paclitaxel as Neoadjuvant Treatment for Patients With Resectable or Borderline Resectable Pancreatic Cancer","route":"/trials/nct06423326/"},{"id":"nct07240766","kind":"trial","name":"HRS-4642 in Combination With Nimotuzumab and Chemotherapy for BRPC With KRAS G12D Mutation","route":"/trials/nct07240766/"},{"id":"nct06435260","kind":"trial","name":"Hypofractionated Radiotherapy +Chemotherapy+ Camrelizumab as 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Koong","route":"/people/albert-koong/"},{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"},{"id":"jurgen-weitz","kind":"person","name":"Jürgen Weitz","route":"/people/jurgen-weitz/"},{"id":"marc-besselink","kind":"person","name":"Marc G. Besselink","route":"/people/marc-besselink/"},{"id":"paula-ghaneh","kind":"person","name":"Paula Ghaneh","route":"/people/paula-ghaneh/"},{"id":"richard-schulick","kind":"person","name":"Richard Schulick","route":"/people/richard-schulick/"},{"id":"theodore-hong","kind":"person","name":"Theodore S. 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