Guideline sources The following summarized guidelines for the evaluation and management of pancreatic cancer are prepared by our editorial team based on guidelines from the Society for Immunotherapy of Cancer (SITC 2023), the American Society for Gastrointestinal Endoscopy (ASGE 2022; 2021; 2016), the American Gastroenterological Association (AGA 2020), the American Society of Clinical Oncology (ASCO 2020; 2019; 2016), the American Society for Radiation Oncology (ASTRO 2019), the European Society of Medical Oncology (ESMO 2019; 2017; 2015), the U.S. Preventive Services Task Force (USPSTF 2019), and the American College of Radiology (ACR 2019). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Calculator Calculator Calculat Eastern Cooperative Oncology G Karnofsky performance status s TNM cl Guidelines https://web.pathway.md/diseases/recXTkkKDUoNwRDio 1/12 6/29/23, 10:52 PM Pancreatic cancer Pathway 1. Screening and diagnosis Indications for screening, general population: As per AGA 2020 guidelines, do not screen average-risk individuals for pancreatic cancer. D As per USPSTF 2019 guidelines, do not screen asymptomatic patients for pancreatic cancer. D Indications for screening, genetically susceptible individuals: As per ASGE 2022 guidelines, consider obtaining annual screening for pancreatic cancer, either with EUS, EUS alternating with MRI or MRI based on patient preference and available expertise, C in individuals at increased risk of pancreatic cancer because of genetic susceptibility, C including individuals with BRCA1 or BRCA2 pathogenic variants. C Show 3 more As per AGA 2020 guidelines, consider obtaining screening for pancreatic cancer in patients determined to be at high risk, including: first-degree relatives of patients with pancreatic cancer with at least 2 affected genetically related relatives patients with genetic syndromes associated with an increased risk of pancreas cancer, including Peutz-Jeghers syndrome and hereditary pancreatitis patients with CDKN2A gene mutation patients with 1 first-degree relatives with pancreatic cancer with Lynch syndrome, and mutations in BRCA1, BRCA2, PALB2, or ATM genes. C Show 11 more Clinical presentation: Recognize that: early symptoms of pancreatic cancer result from a mass effect common presenting symptoms include jaundice, pain, weight loss, and steatorrhea. B Pathology: Recognize that: 95% of pancreatic cancers are adenocarcinomas mucinous lesions of the pancreas have the potential for malignant progression the most frequent precursors are microscopic pancreatic intraepithelial neoplasia, followed by intraductal papillary mucinous neoplasm and mucinous cystic neoplasm multiple combinations of genetic mutations are commonly found in pancreatic cancers. B 2. Diagnostic investigations Clinical evaluation: Obtain a careful evaluation of baseline performance status, symptom burden, and comorbidity profile in patients with pancreatic cancer. A Obtain a full assessment of symptom burden, psychological status, and social support as early as possible, preferably at the first visit, in patients with pancreatic cancer, in order to indicate a need for a formal palliative care consultation and services in most cases. B Imaging for staging: https://web.pathway.md/diseases/recXTkkKDUoNwRDio 2/12 6/29/23, 10:52 PM Pancreatic cancer Pathway As per ASCO 2020 guidelines, obtain multiphase CT of the chest, abdomen, and pelvis to assess the extent of disease. Obtain other staging studies only as dictated by symptoms. B As per ASCO 2019 guidelines, obtain multiphase CT of the abdomen and pelvis using a pancreatic protocol or MRI to assess the anatomic relationships of the primary tumor and to assess for the presence of intra-abdominal metastases. A Show 3 more As per ASGE 2016 guidelines, obtain multidetector pancreatic protocol CT and EUS, as well as MRI and positron emission tomography-CT selectively when appropriate, in the evaluation of patients with suspected solid pancreatic neoplasia. A As per ESMO 2015 guidelines, obtain CT for initial staging of patients with pancreatic cancer. B Show 2 more Laboratory testing: As per ASCO 2019 guidelines, obtain serum CA 19-9 levels and baseline standard laboratory studies in patients with pancreatic cancer. A As per ESMO 2015 guidelines, measure serum CA 19-9 levels in patients with pancreatic cancer. B Genomic testing: obtain early testing for actionable genomic alterations in patients being potential candidates for additional treatment after first-line therapy. Obtain both germline and tumor (somatic) testing, including for MSI/mismatch repair deficiency, BRCA mutations (excluding variants of unknown significance), and NTRK gene fusions, the results of which can lead to therapies, such as poly (ADP-ribose) polymerase inhibitors, PD-L1 checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies. Obtain genomic testing as part of the initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy. A 3. Diagnostic procedures Endoscopic retrograde cholangiopancreatography (solid lesions): do not perform preoperative ERCP in patients with obstructive jaundice due to resectable adenocarcinoma of the pancreas in the absence of cholangitis, unless a substantial delay in operative resection of a symptomatic patient is anticipated. D Endoscopic retrograde cholangiopancreatography (cystic lesions): consider obtaining ERCP for the diagnosis and characterization of suspected main duct intraductal papillary mucinous neoplasms. C EUS-guided fine needle aspiration (cystic lesions): perform EUS-guided FNA of any pancreatic cystic lesion > 3 cm in diameter or when cross-sectional or EUS confirms an epithelial nodule, dilated main pancreatic duct, or suspicious mass lesion. B Show 5 more EUS-guided fine needle aspiration (solid lesions): perform EUS for the evaluation of pancreatic masses and suspected malignancy, particularly when CT detection or evaluation of resectability is equivocal. A Show 2 more https://web.pathway.md/diseases/recXTkkKDUoNwRDio 3/12 6/29/23, 10:52 PM Pancreatic cancer Pathway Pancreatic biopsy: individualize the decision for biopsy of a suspected primary or metastatic pancreatic tumor based on the need for preoperative chemotherapy, resectability, and feasibility of surgery. A 4. Medical management General principles: As per ASCO 2020 guidelines, ensure multidisciplinary collaboration to formulate treatment and care plans and disease management as the standard of care in patients with pancreatic cancer. B As per ESMO 2015 guidelines, ensure multidisciplinary team care for the management of patients with pancreatic cancer. Neoadjuvant chemoradiotherapy, indications: As per ASCO 2019 guidelines, offer neoadjuvant chemotherapy in patients with pancreatic cancer meeting any of the following criteria: radiographic findings suspicious but not diagnostic for extrapancreatic disease performance status or comorbidity profile not currently appropriate (but potentially reversible) for a major abdominal operation radiographic interface between primary tumor and mesenteric vasculature on cross- sectional imaging not meeting appropriate criteria for primary resection CA 19-9 level (in the absence of jaundice) suggestive of disseminated disease. B Show 2 more As per ASTRO 2019 guidelines: Consider offering neoadjuvant therapy in patients with resectable pancreatic cancer. C Consider offering a neoadjuvant therapy regimen of systemic chemotherapy followed by either conventionally fractionated radiotherapy with chemotherapy C or multifraction stereotactic body radiotherapy in patients with borderline resectable pancreatic cancer and select locally advanced pancreatic cancer appropriate for downstaging before surgery. C Neoadjuvant chemoradiotherapy (timing): administer radiotherapy following 2-6 months of systemic chemotherapy in patients with borderline resectable pancreatic cancer receiving neoadjuvant therapy. B Neoadjuvant chemoradiotherapy (dosing of RT): consider administering 4,500-5,040 cGy of radiation in 180-200 cGy fractions in patients with borderline resectable pancreatic cancer selected for neoadjuvant conventionally fractionated radiotherapy and chemotherapy. C Show 2 more Adjuvant chemoradiotherapy, indications: As per ASCO 2019 guidelines, consider offering adjuvant chemoradiotherapy in patients with potentially curable pancreatic cancer not received neoadjuvant chemotherapy and presenting after resection with microscopically positive margins (R1) and/or node-positive disease after completion of 4-6 months of systemic adjuvant chemotherapy. C As per ASCO 2019 guidelines, offer adjuvant chemotherapy for 6 months in all patients with resected pancreatic adenocarcinoma not received preoperative therapy, in the absence of https://web.pathway.md/diseases/recXTkkKDUoNwRDio 4/12 6/29/23, 10:52 PM Pancreatic cancer Pathway medical or surgical contraindications. A Show 3 more As per ASTRO 2019 guidelines: Consider offering adjuvant conventionally fractionated radiotherapy with chemotherapy following surgical resection of pancreatic cancer in selected high-risk patients (high-risk clinical features including positive lymph nodes and margins regardless of tumor location within the pancreas). C Offer adjuvant stereotactic body radiotherapy following surgical resection of pancreatic cancer only in the context of a clinical trial or multi-institutional registry. B As per ESMO 2019 guidelines, offer mFOLFIRINOX as the first adjuvant therapeutic option after resection of pancreatic cancer in selected and fit patients, in view of survival outcomes and associated toxicity profile. A Show 2 more Adjuvant chemoradiotherapy (timing): administer chemoradiation following 4-6 months of systemic chemotherapy in patients with resected pancreatic cancer receiving adjuvant therapy. B Adjuvant chemoradiotherapy (dosing of RT): administer 4500-5400 cGy of radiation in 180- 200 cGy fractions with concurrent 5-fluorouracil-based chemotherapy in patients with resected pancreatic cancer selected for adjuvant conventionally fractionated radiotherapy and chemotherapy. B Definitive chemoradiotherapy, indications: As per ASTRO 2019 guidelines, consider offering a definitive therapy regimen of systemic chemotherapy followed by either conventionally fractionated radiotherapy with chemotherapy, dose-escalated chemoradiation, or multifraction stereotactic body radiotherapy without chemotherapy in patients with locally advanced pancreatic cancer not appropriate for downstaging to eventual surgery. C As per ASCO 2016 guidelines, consider offering chemoradiotherapy in patients with locally advanced, unresectable pancreatic cancer with local progression after induction chemotherapy, but without evidence of systemic spread, meeting the following criteria: first-line chemotherapy treatment is completed or terminated ECOG performance status of 2 adequate comorbidity profile, including adequate hepatic and renal function and hematologic status patient preference. B Show 2 more As per ASCO 2016 guidelines, consider offering stereotactic body radiotherapy for the treatment of patients with locally advanced, unresectable pancreatic cancer. C As per ASCO 2016 guidelines, offer initial chemotherapy with combination regimens in most patients with locally advanced, unresectable pancreatic cancer meeting the following criteria: ECOG performance status of 0-1 favorable comorbidity profile patient preference https://web.pathway.md/diseases/recXTkkKDUoNwRDio 5/12 6/29/23, 10:52 PM Pancreatic cancer Pathway support system for aggressive medical therapy. B Show 3 more Definitive chemoradiotherapy (timing): administer definitive radiotherapy following > 4-6 months of chemotherapy in patients with unresectable or locally advanced pancreatic cancer without systemic progression. B Definitive chemoradiotherapy (dosing of RT): consider administering 5,040- 5,600 cGy of radiation in 175-220 cGy fractions with concurrent chemotherapy in patients with locally advanced pancreatic cancer selected for definitive conventionally fractionated or dose- escalated radiotherapy with chemotherapy. C Show 3 more Technical considerations for radiotherapy (treatment planning): use modulated treatment techniques, such as intensity-modulated radiation therapy and volumetric modulated arc therapy, for planning and delivery of both conventionally fractionated and hypofractionated radiotherapy in patients with localized pancreatic cancer. B Technical considerations for radiotherapy (premedication): Administer prophylactic antiemetics to reduce the rate of nausea in patients with pancreatic cancer undergoing radiotherapy. B Consider administering prophylactic acid suppression medications in patients with pancreatic cancer undergoing radiotherapy. C Technical considerations for radiotherapy (respiratory motion management): obtain patient-specific respiratory motion assessment (4D CT simulation) in patients with pancreatic cancer receiving conventionally fractionated pancreatic radiotherapy or stereotactic body radiotherapy without breath-hold. A Show 2 more Technical considerations for radiotherapy (image guidance): obtain daily image guidance in patients with pancreatic cancer receiving conventionally fractionated radiotherapy. B Show 2 more Palliative systemic therapy, first-line: As per ASCO 2020 guidelines, offer FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) as first-line therapy in patients with metastatic pancreatic cancer meeting all of the following criteria: ECOG performance status of 0-1 favorable comorbidity profile patient preference support system for aggressive medical therapy access to chemotherapy port and infusion pump management services. B Show 3 more Landmark trials: MPACT In patients who had metastatic pancreatic disease with a Karnofsky performance status score 70, nab-paclitaxel plus gemcitabine was superior to gemcitabine monotherapy with respect to median overall survival. https://web.pathway.md/diseases/recXTkkKDUoNwRDio 6/12 6/29/23, 10:52 PM Pancreatic cancer Pathway Von Hoff DD et al. N Engl J Med. 2013 Oct 31. As per ESMO 2015 guidelines, consider offering gemcitabine and nab-paclitaxel as first-line therapy in very selected patients with metastatic pancreatic cancer and ECOG performance status of 2 due to heavy tumor load. C Show 2 more Landmark trials: PRODIGE 4 ACCORD 11 In patients with metastatic pancreatic cancer and an ECOG performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness), FOLFIRINOX was superior to gemcitabine with respect to overall survival. Conroy T et al. N Engl J Med. 2011 May 12. Palliative systemic therapy, second-line: As per ASCO 2020 guidelines, consider offering gemcitabine with nab-paclitaxel as second- line therapy in patients with metastatic pancreatic cancer meeting all of the following criteria: first-line treatment with FOLFIRINOX ECOG performance status of 0-1 relatively favorable comorbidity profile patient preference support system for aggressive medical therapy. C Show 3 more As per ESMO 2017 guidelines, consider offering nanoliposomal irinotecan combined with 5- fluorouracil and leucovorin as second-line therapy in fit patients with metastatic/advanced pancreatic cancer. C Palliative systemic therapy (third-line): insufficient evidence to recommend third-line or greater therapy with a cytotoxic agent in patients with metastatic pancreatic cancer. Encourage participation in clinical trials. I Palliative systemic therapy, targeted therapy: As per SITC 2023 guidelines, offer pembrolizumab monotherapy in patients with previously treated, advanced high MSI/mismatch repair-deficient pancreatic duct adenocarcinoma. Offer dostarlimab monotherapy for mismatch repair-deficient tumors only. B Show 2 more As per ASCO 2020 guidelines, offer larotrectinib or entrectinib in patients with metastatic pancreatic cancer harboring NTRK fusions. B Show 2 more Palliative systemic therapy (treatment duration): insufficient evidence to recommend a specific duration of cancer-directed therapy. Discuss the goals of care and assess the treatment response and tolerability to guide decisions to continue or to hold or terminate cancer-directed therapy. I https://web.pathway.md/diseases/recXTkkKDUoNwRDio 7/12 6/29/23, 10:52 PM Pancreatic cancer Pathway Palliative care: As per ASGE 2021 guidelines, consider placing self-expandable metallic stents or performing surgical gastrojejunostomy in patients with incurable malignant gastric outlet obstruction undergoing palliative intervention. Decide between these approaches based on patient characteristics and preferences, multidisciplinary input, and local expertise. C Show 2 more As per ASCO 2020 guidelines, offer aggressive treatment for pain and symptoms of cancer and/or cancer-directed therapy in patients with locally advanced, unresectable or metastatic pancreatic cancer. B As per ACR 2019 guidelines, place an endoscopic internal biliary catheter with a removable plastic stent or a percutaneous internal/external biliary catheter as the initial therapeutic procedure in patients with common bile duct obstruction. B As per ASCO 2019 guidelines, offer ongoing supportive care for symptom burden resulting from the operation and chemotherapy (preoperative and/or adjuvant)in patients undergone pancreatectomy for potentially curable pancreatic cancer. B As per ASCO 2016 guidelines, consider offering a short course of palliative radiotherapy (conventional or stereotactic body radiotherapy) in patients with locally advanced, unresectable pancreatic cancer meeting the following criteria: prominent local symptoms, such as abdominal pain and/or worsening jaundice and/or gastrointestinal bleeding local infiltration into the gastrointestinal tract causing impending gastric outlet or duodenal obstruction patient preference. C As per ASGE 2016 guidelines, offer palliative radiotherapy to either the primary or select metastatic sites for symptom management in selected patients with metastatic pancreatic cancer. B Show 2 more As per ESMO 2015 guidelines, place an endoscopic expandable metal stent when possible for the management of duodenal obstruction. B Show 3 more Clinical trials: As per ASCO 2016 guidelines, refer patients with locally advanced, unresectable pancreatic cancer not benefited from treatment and having disease progression for a clinical trial. B As per ESMO 2015 guidelines, offer patients with borderline resectable lesions participation in clinical trials wherever possible. B 5. Surgical interventions Primary surgical resection: As per ASCO 2019 guidelines, perform primary surgical resection of the primary tumor and regional lymph nodes in patients meeting all of the following criteria: no clinical evidence for metastatic disease https://web.pathway.md/diseases/recXTkkKDUoNwRDio 8/12 6/29/23, 10:52 PM Pancreatic cancer Pathway performance status and comorbidity profile appropriate for a major abdominal operation radiographic interface between primary tumor and mesenteric vasculature on high- definition cross-sectional imaging CA 19-9 level (in the absence of jaundice) suggestive of potentially curable disease. B As per ESMO 2015 guidelines: Identify tumor clearance for all 7 margins (anterior, posterior, medial or superior mesenteric groove, superior mesenteric artery, pancreatic transection, bile duct, and enteric) in patients with resectable, localized pancreatic cancer. B Remove 15 lymph nodes as standard lymphadenectomy to allow adequate pathologic staging of the disease. B 6. Patient education General counseling: Discuss the goals of care (including a discussion of an advance directive), patient preferences, and support systems with all patients with pancreatic cancer and their caregivers. B Inform all patients with pancreatic cancer about clinical trials, including therapeutic trials in all lines of treatment as well as palliative care, biorepository/biomarker, and observational studies. B 7. Follow-up and surveillance Assessment of treatment response: obtain imaging at 2-3 months from the initiation of therapy to assess first response in patients on active cancer-directed therapy outside of a clinical trial. Obtain CT with contrast as the preferred modality. B Show 3 more Follow-up: Obtain monitoring for recovery of treatment-related toxicities and recurrence in patients completed treatment of potentially curable pancreatic cancer and having no evidence of disease. Consider scheduling visits at 3-6-month intervals. B Insufficient evidence to support the use of serial cross-sectional imaging, prolongation of surveillance intervals over time, and recommend a duration of surveillance in patients with potentially curable pancreatic cancer. I Follow-up patients with locally advanced, unresectable pancreatic cancer completed treatment and having stable disease or no disease progression every 2-3 months including a physical examination, LFTs and renal function tests for a 2-year duration. Consider increasing intervals then to every 6 months. B Show 3 more Clinical findings https://web.pathway.md/diseases/recXTkkKDUoNwRDio 9/12 6/29/23, 10:52 PM Pancreatic cancer Pathway Symptoms Past medical history Back pain Ataxia-telangiectasia Bloating Bone metastasis Change in bowel habits Chronic pancreatitis Dark urine Cystic fibrosis Dyspepsia Diabetes mellitus Dysphagia Familial atypical multiple mole melanoma syndrome Epigastric abdominal pain Gastrointestinal bleeding Generalized pruritus H. pylori infection Loss of appetite Hereditary breast and ovarian cancer syndrome Nausea Pale stools Hereditary chronic pancreatitis Shoulder pain Intrahepatic cholestasis Steatorrhea Li-fraumeni syndrome Vomiting Liver metastasis Weight loss Lung metastasis Obesity Family history Peritoneal metastasis Lynch syndrome Peutz-jeghers syndrome Pancreatic cancer Social history Abdominal exam Alcohol consumption Ascites Tobacco use Epigastric mass Lymphatic exam Integument exam Supraclavicular lymphadenopathy Jaundice Hematological findings Lab findings Anemia Abnormal serum LFTs Iron deficiency serum ALP serum CA 19-9 serum TBIL Studies 2023 Antimicrobial prophylaxis in pancreatoduodenectomy In adults undergoing open pancreatoduodenectomy for any indication, piperacillin-tazobactam was superior to cefoxitin with respect to the rate of postoperative surgical site infection within 30 days. Michael I D'Angelica et al. JAMA. 2023 May 9. 2013 MPACT https://web.pathway.md/diseases/recXTkkKDUoNwRDio 10/12 6/29/23, 10:52 PM Pancreatic cancer Pathway In patients who had metastatic pancreatic disease with a Karnofsky performance status score 70, nab-paclitaxel plus gemcitabine was superior to gemcitabine monotherapy with respect to median overall survival. Von Hoff DD et al. N Engl J Med. 2013 Oct 31. Show 1 more References 1. Manisha Palta, Devon Godfrey, Karyn A Goodman et al. Radiation Therapy for Pancreatic Cancer: Executive Summary of an ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2019 Sep- Oct;9 5 322 332. Open 2. Harry R Aslanian, Jeffrey H Lee, Marcia Irene Canto. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review. Gastroenterology. 2020 Jul;159 1 358 362. Open 3. Davendra P S Sohal, Erin B Kennedy, Pelin Cinar et al. Metastatic Pancreatic Cancer: ASCO Guideline Update. J Clin Oncol. 2020 Aug 5;JCO2001364. 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Am J Gastroenterol. 2015 Feb;110 2 223 62; quiz 263. Open 24. Jean-Marc Dumonceau, Andrea Tringali, Ioannis S Papanikolaou et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy ESGE Clinical Guideline Updated October 2017. Endoscopy. 2018 Sep;50 9 910 930. Open 25. Michael I D'Angelica, Ryan J Ellis, Jason B Liu et al. Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial. JAMA. 2023 May 9;329 18 1579 1588. Open https://web.pathway.md/diseases/recXTkkKDUoNwRDio 12/12