White paper on pancreatic ductal adenocarcinoma from society of abdominal radiology’s disease-focused panel for pancreatic ductal adenocarcinoma: Part I, AJCC staging system, NCCN guidelines, and borderline resectable disease

  • Naveen M. KulkarniEmail author
  • Erik V. Soloff
  • Parag P. Tolat
  • Guillermo P. Sangster
  • Jason B. Fleming
  • Olga R. Brook
  • Zhen Jane Wang
  • Elizabeth M. Hecht
  • Marc Zins
  • Priya R. Bhosale
  • Hina Arif-Tiwari
  • Lorenzo Mannelli
  • Avinash R. Kambadakone
  • Eric P. Tamm


Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Accurate staging of PDAC is an important initial step in the development of a stage-specific treatment plan. Different staging systems/consensus statements convened by different societies and academic practices are currently used. The most recent version of the American Joint Committee on Cancer (AJCC) tumor/node/metastases (TNM) staging system for PDAC has shifted its focus from guiding management to assessing prognosis. In order to preoperatively define the resectability of PDAC and to guide management, additional classification systems have been developed. The National Comprehensive Cancer Network (NCCN) guidelines, one of the most commonly used systems, provide recommendations on the management and the determination of resectability for PDAC. The NCCN divides PDAC into three categories of resectability based on tumor-vessel relationship: ‘resectable,’ ‘borderline resectable,’ and ‘unresectable’. Among these, the borderline disease category is of special interest given its evolution over time and the resulting variations in the definition and the associated recommendations for management between different societies. It is important to be familiar with the evolving criteria, and treatment and follow-up recommendations for PDAC. In this article, the most current AJCC staging (8th edition), NCCN guidelines (version 2.2019—April 9, 2019), and challenges and controversies in borderline resectable PDAC are reviewed.


Pancreatic ductal adenocarcinoma AJCC staging NCCN Borderline resectable pancreatic adenocarcinoma 



The authors wish to thank the members of Society of Abdominal Radiology’s Disease-Focused Panel for Pancreatic Cancer for their suggestions and input in selecting the topics for the white paper (Ajit Goenka, MD; Alexander Guimares MD, PhD; Arnold Friedman, MD; Atif Zaheer, MD; David Hough, MB ChB; Michael Rosenthal, MD, PhD; Namita Gandhi, MD; Ott Le, MD; Richard Do, MD, PhD; Zarine Shah, MD).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67(1):7-30. CrossRefPubMedGoogle Scholar
  2. 2.
    AJCC Cancer Staging Manual. Edge SB et al. New York: Springer. 2010.Google Scholar
  3. 3.
    AJCC Cancer Staging Manual. Eighth Edition. Amin MB et al. New York: Springer 2017.Google Scholar
  4. 4.
    NCCN clinical practice guidelines in oncology - Pancretic adenocarcinoma. V1.2019 - November 8, 2018. Published Accessed on 1/20/2019.
  5. 5.
    Saka B, Balci S, Basturk O, Bagci P, Postlewait LM, Maithel S, Knight J, El-Rayes B, Kooby D, Sarmiento J, Muraki T, Oliva I, Bandyopadhyay S, Akkas G, Goodman M, Reid MD, Krasinskas A, Everett R, Adsay V. Pancreatic Ductal Adenocarcinoma is Spread to the Peripancreatic Soft Tissue in the Majority of Resected Cases, Rendering the AJCC T-Stage Protocol (7th Edition) Inapplicable and Insignificant: A Size-Based Staging System (pT1: </=2, pT2: > 2- </=4, pT3: > 4 cm) is More Valid and Clinically Relevant. Ann Surg Oncol 2016;23(6):2010-2018. CrossRefGoogle Scholar
  6. 6.
    Adsay NV, Bagci P, Tajiri T, Oliva I, Ohike N, Balci S, Gonzalez RS, Basturk O, Jang KT, Roa JC. Pathologic staging of pancreatic, ampullary, biliary, and gallbladder cancers: pitfalls and practical limitations of the current AJCC/UICC TNM staging system and opportunities for improvement. Semin Diagn Pathol 2012;29(3):127-141. CrossRefPubMedGoogle Scholar
  7. 7.
    Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakashima A, Yuasa Y, Kondo N, Ohge H, Sueda T. Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg 2010;211(2):196-204. CrossRefPubMedGoogle Scholar
  8. 8.
    Strobel O, Hinz U, Gluth A, Hank T, Hackert T, Bergmann F, Werner J, Buchler MW. Pancreatic adenocarcinoma: number of positive nodes allows to distinguish several N categories. Ann Surg 2015;261(5):961-969. CrossRefPubMedGoogle Scholar
  9. 9.
    Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 2009;16(7):1727-1733. CrossRefPubMedGoogle Scholar
  10. 10.
    Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM. Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association. Radiology 2014;270(1):248-260. CrossRefPubMedGoogle Scholar
  11. 11.
    Vachiranubhap B, Kim YH, Balci NC, Semelka RC. Magnetic resonance imaging of adenocarcinoma of the pancreas. Top Magn Reson Imaging 2009;20(1):3-9. CrossRefPubMedGoogle Scholar
  12. 12.
    Dolejs S, Zarzaur BL, Zyromski NJ, Pitt HA, Riall TS, Hall BL, Behrman SW. Does Hyperbilirubinemia Contribute to Adverse Patient Outcomes Following Pancreatoduodenectomy? J Gastrointest Surg 2017;21(4):647-656. CrossRefPubMedGoogle Scholar
  13. 13.
    Rijkers AP, Valkema R, Duivenvoorden HJ, van Eijck CH. Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: a meta-analysis. Eur J Surg Oncol 2014;40(7):794-804. CrossRefPubMedGoogle Scholar
  14. 14.
    Wang Z, Chen JQ, Liu JL, Qin XG, Huang Y. FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: a meta-analysis. World J Gastroenterol 2013;19(29):4808-4817. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Allen VB, Gurusamy KS, Takwoingi Y, Kalia A, Davidson BR. Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev 2013(11):CD009323.
  16. 16.
    Ahmed SI, Bochkarev V, Oleynikov D, Sasson AR. Patients with pancreatic adenocarcinoma benefit from staging laparoscopy. J Laparoendosc Adv Surg Tech A 2006;16(5):458-463. CrossRefPubMedGoogle Scholar
  17. 17.
    Morris-Stiff G, Taylor MA. Ca19-9 and pancreatic cancer: Is it really that good? J Gastrointest Oncol 2012;3(2):88-89. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012;3(2):105-119. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297(3):267-277. CrossRefPubMedGoogle Scholar
  20. 20.
    Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 2008;299(9):1019-1026. CrossRefGoogle Scholar
  21. 21.
    Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW, European Study Group for Pancreatic C. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350(12):1200-1210. CrossRefGoogle Scholar
  22. 22.
    Bilimoria KY, Talamonti MS, Sener SF, Bilimoria MM, Stewart AK, Winchester DP, Ko CY, Bentrem DJ. Effect of hospital volume on margin status after pancreaticoduodenectomy for cancer. J Am Coll Surg 2008;207(4):510-519. CrossRefPubMedGoogle Scholar
  23. 23.
    Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, Sauter PK, Hruban RH, Riall TS, Schulick RD, Choti MA, Lillemoe KD, Yeo CJ. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 2006;10(9):1199-1210; discussion 1210-1191. CrossRefGoogle Scholar
  24. 24.
    Tol JA, Gouma DJ, Bassi C, Dervenis C, Montorsi M, Adham M, Andren-Sandberg A, Asbun HJ, Bockhorn M, Buchler MW, Conlon KC, Fernandez-Cruz L, Fingerhut A, Friess H, Hartwig W, Izbicki JR, Lillemoe KD, Milicevic MN, Neoptolemos JP, Shrikhande SV, Vollmer CM, Yeo CJ, Charnley RM, International Study Group on Pancreatic S. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2014;156(3):591-600. CrossRefGoogle Scholar
  25. 25.
    Michalski CW, Kleeff J, Wente MN, Diener MK, Buchler MW, Friess H. Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg 2007;94(3):265-273. CrossRefPubMedGoogle Scholar
  26. 26.
    Esnaola NF, Chaudhary UB, O’Brien P, Garrett-Mayer E, Camp ER, Thomas MB, Cole DJ, Montero AJ, Hoffman BJ, Romagnuolo J, Orwat KP, Marshall DT. Phase 2 trial of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2014;88(4):837-844. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Festa V, Andriulli A, Valvano MR, Uomo G, Perri F, Andriulli N, Corrao S, Koch M. Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies. JOP 2013;14(6):618-625. CrossRefPubMedGoogle Scholar
  28. 28.
    Kim EJ, Ben-Josef E, Herman JM, Bekaii-Saab T, Dawson LA, Griffith KA, Francis IR, Greenson JK, Simeone DM, Lawrence TS, Laheru D, Wolfgang CL, Williams T, Bloomston M, Moore MJ, Wei A, Zalupski MM. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer 2013;119(15):2692-2700. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17(6):1471-1474. CrossRefGoogle Scholar
  30. 30.
    Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15(6):2403-2413. CrossRefPubMedGoogle Scholar
  31. 31.
    Crane CH, Ben-Josef E, Small W, Jr. Chemotherapy for pancreatic cancer. N Engl J Med 2004;350(26):2713-2715; author reply 2713-2715.Google Scholar
  32. 32.
    Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK. Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. Lancet Oncol 2013;14(11):1095-1103. CrossRefPubMedGoogle Scholar
  33. 33.
    Crane CH, Abbruzzese JL, Evans DB, Wolff RA, Ballo MT, Delclos M, Milas L, Mason K, Charnsangavej C, Pisters PW, Lee JE, Lenzi R, Vauthey JN, Wong AB, Phan T, Nguyen Q, Janjan NA. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys 2002;52(5):1293-1302.CrossRefGoogle Scholar
  34. 34.
    Huang J, Robertson JM, Margolis J, Balaraman S, Gustafson G, Khilanani P, Nadeau L, Jury R, McIntosh B. Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreas cancer. Radiother Oncol 2011;99(2):114-119. CrossRefPubMedGoogle Scholar
  35. 35.
    Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist 2013;18(5):543-548. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bickenbach KA, Gonen M, Tang LH, O’Reilly E, Goodman K, Brennan MF, D’Angelica MI, Dematteo RP, Fong Y, Jarnagin WR, Allen PJ. Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease. Ann Surg Oncol 2012;19(5):1663-1669. CrossRefPubMedGoogle Scholar
  37. 37.
    Chatzizacharias NA, Tsai S, Griffin M, Tolat P, Ritch P, George B, Barnes C, Aldakkak M, Khan AH, Hall W, Erickson B, Evans DB, Christians KK. Locally advanced pancreas cancer: Staging and goals of therapy. Surgery 2018;163(5):1053-1062. CrossRefPubMedGoogle Scholar
  38. 38.
    Mehta VK, Fisher G, Ford JA, Poen JC, Vierra MA, Oberhelman H, Niederhuber J, Bastidas JA. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg 2001;5(1):27-35.CrossRefGoogle Scholar
  39. 39.
    Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13(8):1035-1046. CrossRefPubMedGoogle Scholar
  40. 40.
    Deal S, Nathan D, Rocha FG. Modified Appleby procedure for locally advanced pancreatic cancer. Am J Surg 2018;215(5):853-855. CrossRefPubMedGoogle Scholar
  41. 41.
    Katz MH, Crane CH, Varadhachary G. Management of borderline resectable pancreatic cancer. Semin Radiat Oncol 2014;24(2):105-112. CrossRefPubMedGoogle Scholar
  42. 42.
    Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PW, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118(23):5749-5756. CrossRefPubMedGoogle Scholar
  43. 43.
    Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, Asbun HJ, Bassi C, Buchler M, Charnley RM, Conlon K, Cruz LF, Dervenis C, Fingerhutt A, Friess H, Gouma DJ, Hartwig W, Lillemoe KD, Montorsi M, Neoptolemos JP, Shrikhande SV, Takaori K, Traverso W, Vashist YK, Vollmer C, Yeo CJ, Izbicki JR, International Study Group of Pancreatic S. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2014;155(6):977-988. CrossRefGoogle Scholar
  44. 44.
    Toesca DAS, Koong AJ, Poultsides GA, Visser BC, Haraldsdottir S, Koong AC, Chang DT. Management of Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2018;100(5):1155-1174. CrossRefPubMedGoogle Scholar
  45. 45.
    Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, Kindler HL, Alberts SR, Philip P, Lowy AM, Pisters PW, Posner MC, Berlin JD, Ahmad SA. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 2013;20(8):2787-2795. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Soloff EV, Zaheer A, Meier J, Zins M, Tamm EP. Staging of pancreatic cancer: resectable, borderline resectable, and unresectable disease. Abdom Radiol (NY) 2018;43(2):301-313. CrossRefGoogle Scholar
  47. 47.
    Illuminati G, Carboni F, Lorusso R, D’Urso A, Ceccanei G, Papaspyropoulos V, Pacile MA, Santoro E. Results of a pancreatectomy with a limited venous resection for pancreatic cancer. Surg Today 2008;38(6):517-523. CrossRefPubMedGoogle Scholar
  48. 48.
    Hamidian Jahromi A, Jafarimehr E, Dabbous HM, Chu Q, D’Agostino H, Shi R, Wellman GP, Zibari GB, Shokouh-Amiri H. Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival. JOP 2014;15(5):433-441. CrossRefPubMedGoogle Scholar
  49. 49.
    Hoffe S, Rao N, Shridhar R. Neoadjuvant vs adjuvant therapy for resectable pancreatic cancer: the evolving role of radiation. Semin Radiat Oncol 2014;24(2):113-125. CrossRefPubMedGoogle Scholar
  50. 50.
    Donahue TR, Isacoff WH, Hines OJ, Tomlinson JS, Farrell JJ, Bhat YM, Garon E, Clerkin B, Reber HA. Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery. Arch Surg 2011;146(7):836-843. CrossRefPubMedGoogle Scholar
  51. 51.
    Dholakia AS, Hacker-Prietz A, Wild AT, Raman SP, Wood LD, Huang P, Laheru DA, Zheng L, De Jesus-Acosta A, Le DT, Schulick R, Edil B, Ellsworth S, Pawlik TM, Iacobuzio-Donahue CA, Hruban RH, Cameron JL, Fishman EK, Wolfgang CL, Herman JM. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships. J Radiat Oncol 2013;2(4):413-425. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Naveen M. Kulkarni
    • 1
    Email author
  • Erik V. Soloff
    • 2
  • Parag P. Tolat
    • 1
  • Guillermo P. Sangster
    • 3
  • Jason B. Fleming
    • 4
  • Olga R. Brook
    • 5
  • Zhen Jane Wang
    • 6
  • Elizabeth M. Hecht
    • 7
  • Marc Zins
    • 8
  • Priya R. Bhosale
    • 9
  • Hina Arif-Tiwari
    • 10
  • Lorenzo Mannelli
    • 11
  • Avinash R. Kambadakone
    • 12
  • Eric P. Tamm
    • 9
  1. 1.Department of RadiologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of RadiologyUniversity of WashingtonSeattleUSA
  3. 3.Department of RadiologyLSU Health – Shreveport Ochsner-LSU Health – ShreveportShreveportUSA
  4. 4.Gastrointestinal OncologyMoffitt Cancer CenterTampaUSA
  5. 5.Department of RadiologyBeth Israel Deaconess Medical CenterBostonUSA
  6. 6.Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoUSA
  7. 7.Department of RadiologyColumbia University Medical CenterNew YorkUSA
  8. 8.Department of RadiologyGroupe Hospitalier Paris Saint-JosephParisFrance
  9. 9.Abdominal Imaging DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  10. 10.Department of RadiologyUniversity of Arizona College of MedicineTucsonUSA
  11. 11.IRCCS SDNNaplesItaly
  12. 12.Department of RadiologyMassachusetts General HospitalBostonUSA

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