Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
2023; Elsevier BV; Volume: 34; Issue: 11 Linguagem: Inglês
10.1016/j.annonc.2023.08.009
ISSN1569-8041
AutoresThierry Conroy, Per Pfeiffer, Valérie Vilgrain, Ángela Lamarca, Thomas Seufferlein, Eileen M. O’Reilly, Thilo Hackert, Talia Golan, Gerald W. Prager, Karin Haustermans, Arndt Vogel, Michel Ducreux,
Tópico(s)Pancreatitis Pathology and Treatment
Resumo•The guideline covers diagnosis, staging, risk assessment, treatment, disease monitoring and follow-up.•The multidisciplinary expert author group is from different institutions and countries in Europe, Asia and the USA.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•ESMO-MCBS and ESCAT scores provide levels of evidence for treatment choices, including targeted therapies.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach. Details on incidence and epidemiology are covered in the Supplementary Material Section 1, available at https://doi.org/10.1016/j.annonc.2023.08.009. The opportunity to detect pancreatic cancer (PC) when potentially curable depends on early diagnosis and an ability to identify and screen high-risk populations before symptoms arise. Identification of a high-risk population is challenging and optimal screening tools remain unclear.1Pereira S.P. Oldfield L. Ney A. et al.Early detection of pancreatic cancer.Lancet Gastroenterol Hepatol. 2020; 5: 698-710Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar Older age is the strongest risk factor; incidence peaks at 65-69 years in males and 75-79 years in females.2GBD 2017 Pancreatic Cancer CollaboratorsThe global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2019; 4: 934-947Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar A pooled analysis of 117 meta-analyses assigned a relative risk to a number of common risk factors (Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2023.08.009).3Maisonneuve P. Lowenfels A.B. Risk factors for pancreatic cancer: a summary review of meta-analytical studies.Int J Epidemiol. 2015; 44: 186-198Crossref PubMed Google Scholar The vast majority (>80%) of PCs arise due to sporadically occurring somatic mutations. Only a small proportion are due to inherited deleterious germline mutations.1Pereira S.P. Oldfield L. Ney A. et al.Early detection of pancreatic cancer.Lancet Gastroenterol Hepatol. 2020; 5: 698-710Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar Familial PC, defined as at least two first-degree relatives with PC, accounts for only 4%-10% of all cases. Variants in BRCA2 are the most common genetic abnormalities seen in familial PC. Other familial syndromes linked to PC are listed in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2023.08.009. Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries. Currently, in high-risk individuals, annual endoscopic ultrasound (EUS) and/or pancreatic magnetic resonance imaging (MRI) are the procedures of choice for surveillance.4Stjepanovic N. Moreira L. Carneiro F. et al.Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2019; 30: 1558-1571Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar Surveillance programmes usually begin at age 50 years (or 10 years earlier than the age of the youngest affected relative). Prospective surveillance data in high-risk individuals demonstrated high rates of resectability and encouraging observations of long-term survival.5Owens D.K. Davidson K.W. Krist A.H. et al.Screening for pancreatic cancer.JAMA. 2019; 322: 438Crossref PubMed Scopus (0) Google Scholar, 6Yurgelun M.B. Building on more than 20 years of progress in pancreatic cancer surveillance for high-risk individuals.J Clin Oncol. 2022; 40: 3230-3234Crossref PubMed Scopus (0) Google Scholar, 7Klatte D.C.F. Boekestijn B. Wasser M. et al.Pancreatic cancer surveillance in carriers of a germline CDKN2A pathogenic variant: yield and outcomes of a 20-year prospective follow-up.J Clin Oncol. 2022; 40: 3267-3277Crossref PubMed Scopus (18) Google Scholar, 8Dbouk M. Katona B.W. Brand R.E. et al.The multicenter cancer of pancreas screening study: impact on stage and survival.J Clin Oncol. 2022; 40: 3257-3266Crossref PubMed Scopus (4) Google Scholar, 9Sawhney M.S. Calderwood A.H. Thosani N.C. et al.ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations.Gastrointest Endosc. 2022; 95: 817-826Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In sporadic PC, the major risk factors are tobacco, Helicobacter pylori infection and factors related to dietary habits (high red meat, high alcohol intake, low fruit and vegetable intake, overweight/obesity and type 2 diabetes mellitus).2GBD 2017 Pancreatic Cancer CollaboratorsThe global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2019; 4: 934-947Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar,3Maisonneuve P. Lowenfels A.B. Risk factors for pancreatic cancer: a summary review of meta-analytical studies.Int J Epidemiol. 2015; 44: 186-198Crossref PubMed Google Scholar,10Yu J. Yang X. He W. et al.Burden of pancreatic cancer along with attributable risk factors in Europe between 1990 and 2019, and projections until 2039.Int J Cancer. 2021; 149: 993-1001Crossref PubMed Scopus (52) Google Scholar Chronic pancreatitis, irrespective of the cause (alcohol abuse, smoking, genetic mutations), is a risk factor for PC. A proportion of the risk factors associated with PC are potentially modifiable, affording a unique opportunity for primary prevention that is yet to be realised. •Not smoking, limiting alcohol intake and reaching and maintaining a healthy weight are highly recommended to reduce the risk of PC [III, A].•Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries [III, A].•Surveillance in expert centres, usually beginning at age 50 years (or 10 years earlier than the age of the youngest affected relative), is recommended in high-risk individuals to detect early PC [III, A].oAnnual EUS and/or pancreatic MRI are preferred for surveillance [IV, B]. Approximately three quarters of PCs arise in the head of the pancreas, 17%-26% in the body and tail and the remaining 5%-8% in multiple pancreatic locations.11Latenstein A.E.J. van der Geest L.G.M. Bonsing B.A. et al.Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma.Eur J Cancer. 2020; 125: 83-93Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar,12Kirkegård J. Bojesen A.B. Nielsen M.F. et al.Trends in pancreatic cancer incidence, characteristics, and outcomes in Denmark 1980-2019: a nationwide cohort study.Cancer Epidemiol. 2022; 80102230Crossref PubMed Scopus (2) Google Scholar Tumours located in the body and tail are likely to be diagnosed at a more advanced stage relative to head tumours, as these latter tumours develop symptoms related to obstruction of the common bile duct and/or the pancreatic duct. Common presenting symptoms of PC include jaundice (head tumours), abdominal pain, weight loss, steatorrhoea and new onset or worsening of pre-existing diabetes. Tumours can grow locally into the duodenum (proximal for head tumours and distal for body/tail tumours) and result in duodenal obstruction. The imaging work-up aims to assess:•Tumour location and size;•Peripancreatic venous and arterial vascular involvement; and•Locoregional involvement and metastatic extent (liver, lymph nodes, peritoneum and lung). Computed tomography (CT) is the main modality for diagnosing PC. CT staging should include chest, abdomen and pelvis. In case of jaundice due to an obstructive head PC, the presence of bile duct dilation is an important landmark for delineation of these head PCs. Technical optimisation is essential and key factors for high-quality CT are the following: (i) multiphase thin-section images including pancreatic, arterial and portal venous phases; and (ii) intravenous iodinated non-ionic contrast agent injection at 1.5 ml/kg and at a rate of 4-5 ml/s. Diagnostic criteria for PC include direct signs such as a hypovascular tumour and indirect signs such as main pancreatic and/or common bile duct dilation, segmental atrophy of the parenchyma and abnormalities in pancreatic contour. The attenuation gradient between the tumour and the adjacent pancreas is greater in the pancreatic phase than in subsequent phases, and this phase performs best for tumour detection.13Zins M. Matos C. Cassinotto C. Pancreatic adenocarcinoma staging in the era of preoperative chemotherapy and radiation therapy.Radiology. 2018; 287: 374-390Crossref PubMed Scopus (100) Google Scholar Delayed-phase CT increases the sensitivity for detecting small primary tumours.14Fukukura Y. Kumagae Y. Fujisaki Y. et al.Adding delayed phase images to dual-phase contrast-enhanced CT increases sensitivity for small pancreatic ductal adenocarcinoma.AJR Am J Roentgenol. 2021; 217: 888-897Crossref PubMed Scopus (0) Google Scholar CT should be carried out in the 4 weeks before starting therapy. Abdominal MRI is usually used when CT is inconclusive, such as for isoattenuating tumours or when a contrast-enhanced CT is contraindicated; in this case staging must include chest CT. The proportion of isoattenuating PC ranges from 5% to 17%.13Zins M. Matos C. Cassinotto C. Pancreatic adenocarcinoma staging in the era of preoperative chemotherapy and radiation therapy.Radiology. 2018; 287: 374-390Crossref PubMed Scopus (100) Google Scholar MRI sequences should include T2-, fat suppressed T1- and diffusion-weighted sequences and magnetic resonance cholangiopancreatography (two-dimensional and/or three-dimensional), followed by multiphasic contrast-enhanced sequences. Several studies have demonstrated that MRI, including diffusion-weighted sequences, is more sensitive than CT for depicting small liver metastases. According to three series and a meta-analysis, MRI identified liver metastases that were not visible with CT in 10%-23% of cases. Thus, the rate of unnecessary laparotomy in potentially operable patients may be reduced.15Hong S.B. Choi S.H. Kim K.W. et al.Meta-analysis of MRI for the diagnosis of liver metastasis in patients with pancreatic adenocarcinoma.J Magn Reson Imaging. 2019; 51: 1737-1744Crossref PubMed Scopus (0) Google Scholar The imaging reports should detail tumour characteristics, tumour-to-vessel contact for each peripancreatic vessel, locoregional involvement (liver, lymphadenopathy, omentum) and the presence/absence of distant metastases. The use of standardised reporting templates proposed by a multispecialist group of experts in PC16Al-Hawary M.M. Francis I.R. Chari S.T. et al.Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the society of abdominal radiology and the American pancreatic association.Gastroenterology. 2014; 146: 291-304.e291Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar is recommended, as it has been shown that structured reports for PC staging significantly reduce the number of missing morphological and vascular features compared with free-text reports.17Dimarco M. Cannella R. Pellegrino S. et al.Impact of structured report on the quality of preoperative CT staging of pancreatic ductal adenocarcinoma: assessment of intra- and inter-reader variability.Abdom Radiol. 2019; 45: 437-448Crossref Scopus (11) Google Scholar A pathognomonic finding is the presence of a double duct sign identified at endoscopic retrograde cholangiopancreatography (ERCP) or on imaging related to obstruction of the bile and pancreatic ducts. ERCP, however, has little diagnostic value over CT or MRI for the evaluation of patients with PC. Positron emission tomography (PET)–CT is not routinely recommended for the diagnosis of PC, in view of the overlap of PC findings with autoimmune and chronic pancreatitis.18Wu L.-M. Hu J.-N. Hua J. et al.Diagnostic value of diffusion-weighted magnetic resonance imaging compared with fluorodeoxyglucose positron emission tomography/computed tomography for pancreatic malignancy: a meta-analysis using a hierarchical regression model.J Gastroenterol Hepatol. 2012; 27: 1027-1035Crossref PubMed Scopus (0) Google Scholar Furthermore, a meta-analysis of 17 clinical studies that recruited 1343 patients showed that PET–CT had no superiority over CT in identifying distant metastasis, with a 7.8% false-positive rate and a 9.8% false-negative rate.19Wang L. Dong P. Wang W.G. et al.Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: a meta-analysis.Int J Surg. 2017; 46: 119-125Crossref PubMed Scopus (0) Google Scholar EUS is indicated for tumour staging in selected cases, e.g. isodense tumour at CT or when assessing venous involvement. EUS can also be used to biopsy pancreas, lymph nodes and lesions in the left liver or to sample ascites. Biopsy is indicated for patients requiring differential diagnosis with benign chronic pancreatitis or a histological diagnosis, such as patients initiating chemotherapy (ChT); biopsy, however, is not routinely advised if surgical resection is planned. For localised disease, EUS-guided fine-needle biopsy is preferred, allows tissue confirmation of malignancy and is recommended over CT-guided biopsy. It is advised that at least one attempt be carried out unless unsafe for the patient. After two inconclusive attempts, treatment may begin without histological proof, provided multidisciplinary tumour board (MDTB) discussion, imaging and carbohydrate antigen (CA) 19-9 are consistent with a diagnosis of malignancy. Percutaneous biopsy of the most easily accessible tumour site can be carried out to confirm metastatic disease. PET–CT can be considered for staging in the presence of non-metastatic disease on CT for patients who will receive local cancer treatment [surgery or radiotherapy (RT)]. The use of staging laparoscopy to evaluate peritoneal metastasis in resectable PC or borderline resectable PC (BRPC) has been advocated by some authors but is not routinely carried out.20Callery M.P. Chang K.J. Fishman E.K. et al.Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement.Ann Surg Oncol. 2009; 16: 1727-1733Crossref PubMed Scopus (717) Google Scholar Findings from a meta-analysis suggest that laparoscopy could be useful in this case.21Ta R. O’Connor Donal B. Sulistijo A. et al.The role of staging laparoscopy in resectable and borderline resectable pancreatic cancer: a systematic review and meta-analysis.Dig Surg. 2018; 36: 251-260Crossref PubMed Scopus (0) Google Scholar Peritoneal lavage cytology in PC remains controversial due to its low sensitivity but is increasingly used, especially in Japan and Korea. Current studies are evaluating its prognostic impact.22Tsuchida H. Fujii T. Mizuma M. et al.Prognostic importance of peritoneal washing cytology in patients with otherwise resectable pancreatic ductal adenocarcinoma who underwent pancreatectomy: a nationwide, cancer registry-based study from the Japan Pancreas Society.Surgery. 2019; 166: 997-1003Abstract Full Text Full Text PDF PubMed Google Scholar PCs arise from both the exocrine and endocrine parenchyma; however, ∼95% arise within the exocrine portion from ductal epithelium, acinar cells or connective tissue. Only 2% of tumours of the exocrine pancreas are benign. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for ∼80% of all PCs. Microscopically, these neoplasms vary from well-differentiated duct-forming carcinomas (that may mimic non-neoplastic glands) to poorly differentiated carcinomas, with epithelial differentiation demonstrable only on immunolabelling. PDAC typically elicits an intense stromal reaction.23Rishi A. Goggins M. Wood L.D. et al.Pathological and molecular evaluation of pancreatic neoplasms.Semin Oncol. 2015; 42: 28-39Crossref PubMed Google Scholar Other variants of PC, such as adenosquamous carcinoma and undifferentiated carcinomas with osteoclast-like giant cells, are associated with a poorer prognosis. Conversely, pancreatic acinar-cell carcinomas have a slightly better prognosis than PDAC.24Egal A. Cros J. Svrcek M. et al.Prognostic factors of acinar cell carcinomas.Pancreas. 2019; 48: 1393-1396Crossref PubMed Scopus (7) Google Scholar Pancreatic neuroendocrine tumours and neuroendocrine carcinomas are the second most frequent PC, a topic which is covered elsewhere.25Pavel M. Oberg K. Falconi M. et al.Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2020; 31: 844-860Abstract Full Text Full Text PDF PubMed Scopus (468) Google Scholar Cystic neoplasms represent 10%-15% of cystic lesions of the pancreas. The most commonly encountered cystic neoplasms include serous cystadenoma, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (either cystadenoma or cystadenocarcinoma). Mucinous lesions have potential for malignant progression and/or may harbour a malignancy at the time of diagnosis.26Buerlein R.C.D. Shami V.M. Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know.Ther Adv Gastrointest Endosc. 2021; 1426317745211045769PubMed Google Scholar The non-mucinous lesions have no malignant potential. The most frequent precursor lesions for PC are pancreatic intraepithelial neoplasia (PanIN), followed by IPMN and mucinous cystic neoplasm. PanIN are microscopic ( 90% of PCs;•Inactivation of tumour suppressor genes such as TP53, p16/CDKN2A and SMAD4;•Inactivation of genome maintenance genes, such as hMLH1 and MSH2, which control DNA damage repair (DDR). Most of these mutations are somatic aberrations; and•Alterations in genes specifically involved in the homologous recombination repair (HRR) pathway, such as BRCA1 and BRCA2. Most of these mutations are germline. Patterns of structural variation in chromosomes classify PC into four subtypes with potential clinical utility. The subtypes are termed ‘stable’, ‘locally rearranged’, ‘scattered’ and ‘unstable’. In the unstable group, a high rate of DNA variations is associated with significant defects in DDR, particularly in the HRR system. Additionally, genomic instability cosegregates with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DDR deficiency. Overall, alterations in DDR/HRR pathways are observed in 24% of patients. PC has also been classified using transcriptional networks. Two main clinically relevant subtypes have been identified. Squamous and ‘basal-like’ phenotypes share important aspects including high tumour grade, metastatic disease, chemo-resistance and poor prognosis. The ‘classical’ subtype has a more favourable outcome.27Aung K.L. Fischer S.E. Denroche R.E. et al.Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial.Clin Cancer Res. 2018; 24: 1344-1354Crossref PubMed Scopus (330) Google Scholar The genomics-driven COMPASS trial has provided the first evidence that ChT response rates differ among patients with advanced PDAC according to the transcriptomic profile.27Aung K.L. Fischer S.E. Denroche R.E. et al.Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial.Clin Cancer Res. 2018; 24: 1344-1354Crossref PubMed Scopus (330) Google Scholar KRAS-wild type (wt) metastatic PDAC has been established as a unique molecular entity, for which therapeutic opportunities exist that extend beyond gene fusion events. Multigene sequencing is a useful tool to screen for rare, potentially actionable findings.28Mosele F. Remon J. Mateo J. et al.Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.Ann Oncol. 2020; 31: 1491-1505Abstract Full Text Full Text PDF PubMed Scopus (542) Google Scholar,29Philip P.A. Azar I. Xiu J. et al.Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma.Clin Cancer Res. 2022; 28: 2704-2714Crossref PubMed Scopus (42) Google Scholar CA 19-9 is not useful for screening for PC. An increase in serum levels is identified in almost 80% of patients with advanced PC, which makes CA 19-9 significant as a prognostic factor. However, CA 19-9 is undetectable in patients with Lewis antigen-negative phenotypes. A preoperative serum CA 19-9 level ≥500 IU/ml indicates a worse prognosis after surgery, and immediate surgery should be considered with caution in these cases.30Isaji S. Mizuno S. Windsor J.A. et al.International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017.Pancreatology. 2018; 18: 2-11Crossref PubMed Scopus (391) Google Scholar An algorithm for diagnostic work-up of suspected PC is given in Figure 1. •Multiphasic contrast-enhanced thoracic-abdominal and pelvic CT, including late arterial phase and portal venous phase, should be used as the first-line imaging modality for suspected PC [III, A].•It is recommended that, in case of jaundice due to an obstructive head PC, imaging should be carried out before biliary drainage or stenting [IV, A].•Imaging should be carried out in the 4 weeks before starting treatment [III, A].•Abdominal MRI may be used when CT cannot be carried out, is inconclusive or for pancreatic cystic lesions [IV, C]; in this case chest CT is mandatory [III, A].•Dedicated imaging protocols are suggested [IV, B]. Comprehensive analysis of imaging findings should be incorporated in standardised reporting templates [IV, A].•PET–CT is not recommended for diagnosis of primary tumours [III, D] but may be useful for staging localised tumours and in cases where the presence of distant metastases is uncertain (doubtful imaging or high CA 19-9) [III, B].•Hepatic MRI is recommended before surgery to confirm the absence of small liver metastases [III, B].•Cytology or biopsy proof of PC should be obtained before initiation of ChT in localised disease, preferably by EUS guidance [III, A].•All patients with localised disease should have imaging reviewed at an MDTB with experts in pancreas imaging, pancreas surgery and oncology [III, A]. •Patients with family history and high-risk individuals should undergo genetic counselling [III, A].•KRAS and BRCA testing are generally recommended [IV, B].•If a KRAS-wt tumour is identified with next-generation sequencing, additional profiling can be carried out to evaluate for rare, potentially actionable findings [IV, B].oFor patients with metastatic PC and KRAS-wt tumours, microsatellite instability (MSI) status, NTRK fusion status and other rare fusions should be assessed [III, B].oIf multigene sequencing is not carried out, MSI and NTRK fusions can be detected using standard methods [IV, B].•CA 19-9 can be used as a serum marker to measure disease burden and potentially guide treatment decisions [III, B]. The prognosis of PC is primarily determined by tumour-related factors captured in the Union for International Cancer Control (UICC) 2017 tumour–node–metastasis (TNM) staging system. In the eighth edition, the T stage is based on size (except for pT4 tumours), as shown in Supplementary Tables S3 and S4, available at https://doi.org/10.1016/j.annonc.2023.08.009. Furthermore, the N stage is subdivided into N1 and N2 according to the number of positive regional lymph nodes. Aside from the UICC TNM and the National Comprehensive Cancer Network (NCCN) criteria,31National Comprehensive Cancer Network. Pancreatic Adenocarcinoma, Version 2.2022. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).Google Scholar several studies have indicated the importance of tumour biology and host-related conditional factors. In 2017, the International Association of Pancreatology (IAP) released a definition of BRPC based on three dimensions: (i) anatomical; (ii) biological, including serum CA 19-9 level >500 IU/ml and regional lymph node metastases diagnosed by biopsy or PET–CT; and (iii) conditional, including Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.30Isaji S. Mizuno S. Windsor J.A. et al.International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017.Pancreatology. 2018; 18: 2-11Crossref PubMed Scopus (391) Google Scholar The author panel believes that these factors are also important for evaluating the tumour resectability. Another major factor determining the prognosis of patients with resected tumours is the feasibility to receive and complete adjuvant treatment.32Conroy T. Hammel P. Hebbar M. et al.FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer.N Engl J Med. 2018; 379: 2395-2406Crossref PubMed Scopus (1649) Google Scholar,33Von Hoff D.D. Ervin T. Arena F.P. et al.Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med. 2013; 369: 1691-1703Crossref PubMed Scopus (4641) Google Scholar In advanced disease, the factors defining a worse prognosis are determined from the key phase III studies. Impaired general condition (ECOG PS ≥2), age >65 years, albumin <35 g/l, presence of synchronous metastases, liver metastases, number of metastatic sites and high serum CA 19-9 are negatively associated with survival.33Von Hoff D.D. Ervin T. Arena F.P. et al.Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med. 2013; 369: 1691-1703Crossref PubMed Scopus (4641) Google Scholar,34Conroy T. Desseigne F. Ychou M. et al.FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.N Engl J Med. 2011; 364: 1817-1825Crossref PubMed Scopus (5657) Google Scholar On completion of staging procedures and discussion in an MDTB, tumours should be categorised as resectable, borderline resectable, locally advanced or advanced/metastatic. A treatment decision must be taken in accordance with these findings, accounting for factors such as nutritional status, PS and comorbidities. •Tumours should be staged according to the UICC TNM 8th edition staging system [III, A].•Resectability can be assessed using both anatomical NCCN criteria and biological and conditional features following the IAP consensus [III, B].•MDTB discussion in expert centres is required to define a recommended treatment strategy for patients with PC [III, A]. A treatment algorithm for local and locoregional disease is provided in Figure 2. Surgical resection is the only potentially curative treatment for PC. Following radiological evaluation, only patients with a high probability of surgical resection with no tumour at the margin (R0; defined as no cancer cells within 1 mm of all resection margins) are good candidates for upfront surgery. An expert consensus group has developed criteria to define tumour resectability, to improve patient selection and the rate of R0 resections.20Callery M.P. Chang K.J. Fishman E.K. et al.Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement.Ann Surg Oncol. 2009; 16: 1727-1733Crossref PubMed Scopus (717) Google Scholar,35Bockhorn M. Uzunoglu F.G. Adham M. et al.Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).Surgery. 2014; 155: 977-988Abstract Full Text Full Text PDF PubMed Google Scholar According to the degree of contact between the tumour and the peripancreatic vessels [superior mesenteric vein (SMV) or portal vein (PV), superior mesenteric artery (SMA), coeliac trunk and common hepatic artery], tumours are classified as resectable, borderline resectable, locally advanced or advanced/metastatic. For resectable tumours, initial surgery remains the standard of care. These criteria have been adopted in the NCCN guidelines.31National Comprehensive Cancer Network. Pancreatic Adenocarcinoma, Version 2.2022. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).Google Scholar Although there are several other classification systems that assess tumour resectability, the NCCN criteria: (i) are the most commonly used by far; (ii) are regularly updated—the authors refer to NCCN Guidelines Version 2.2022 here;31National Comprehensive Cancer Network. Pancreatic Adenocarcinoma, Version 2.2022. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).Google Scholar and (iii) have been extensively validated; the latest update was shown to be more accurate than prior versions.36Park S.-J. Jang S. Han J.K. et al.Preoperative assessment of the resectability of pancreatic ductal adenocarcinoma on CT according to the NCCN Guidelines focusing on SMA/SMV branch invasion.Eur Radiol. 2021; 31: 6889-6897Crossref PubMed Scopus (9) Google Scholar The location and size of the tumour determine the type of surgery. Patients with tumours in the head of the pancreas undergo pancreatoduodenectomy (Whipple procedure). Dissection of the right hemi-circumference of the SMA to the right of the coeliac trunk is recommended to obtain a good medial clear
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