Skip to main content

Advertisement

SpringerLink
Log in

Current Concepts in the Treatment of Resectable Pancreatic Cancer

  • Gastrointestinal Cancers (J Meyer, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The diagnosis of pancreatic cancer carries with it a high mortality rate. Despite advances in the field, this has remained relatively unchanged over the last few decades. Current options for the treatment of resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction with the historical data that support them. We will focus on updates in treatment guidelines and ongoing clinical trials of interest.

Recent Findings

For localized disease, standard of care includes resection followed by adjuvant chemotherapy ± chemoradiation. Recently, a report was published supporting the use of doublet therapy with gemcitabine and capecitabine (as opposed to gemcitabine monotherapy), which prompted a practice-changing update to major treatment guidelines. Multiple trials using neoadjuvant treatment, novel therapies, and different forms of radiation are ongoing.

Summary

Although pancreatic cancer is an active area of research, outcomes remain dismal. Clinical trials will need to be more robust and innovative to drastically improve survival statistics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. American Cancer Society. Cancer Statistics Center. http://cancerstatisticscenter.cancer.org. Accessed April 4.

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. https://doi.org/10.1002/ijc.29210.

    Article  CAS  PubMed  Google Scholar 

  3. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21. https://doi.org/10.1158/0008-5472.CAN-14-0155.

    Article  CAS  PubMed  Google Scholar 

  4. SEER Stat Fact Sheets: Pancreas cancer. https://seer.cancer.gov/. Accessed April 4.

  5. Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16(4):836–47. https://doi.org/10.1245/s10434-008-0295-2.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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):1727–33. https://doi.org/10.1245/s10434-009-0408-6.

    Article  PubMed  Google Scholar 

  7. Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, et al. Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association. Radiology. 2014;270(1):248–60. https://doi.org/10.1148/radiol.13131184.

    Article  PubMed  Google Scholar 

  8. National Comprehensive Cancer Network. Pancreatic Adenocarcinoma (Version 2.2016). https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site. Accessed February 1.

  9. Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206(5):833–46; discussion 46-8. https://doi.org/10.1016/j.jamcollsurg.2007.12.020.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E, et al. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg. 2016;151(8):e161137. https://doi.org/10.1001/jamasurg.2016.1137.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(21):2541–56. https://doi.org/10.1200/jco.2016.67.5553.

    Article  PubMed  Google Scholar 

  12. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903.

    Article  CAS  PubMed  Google Scholar 

  13. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10. https://doi.org/10.1056/NEJMoa032295.

    Article  CAS  PubMed  Google Scholar 

  14. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77. https://doi.org/10.1001/jama.297.3.267.

    Article  CAS  PubMed  Google Scholar 

  15. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81. https://doi.org/10.1001/jama.2013.279201.

    Article  CAS  PubMed  Google Scholar 

  16. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81. https://doi.org/10.1001/jama.2010.1275.

    Article  CAS  PubMed  Google Scholar 

  17. • Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388(10041):248–57. https://doi.org/10.1016/S0140-6736(16)30583-9. Survival statistics in this trial are significantly improved over standard of care; however, treatment has not been expanded to a more broad population outside of Japan.

    Article  CAS  PubMed  Google Scholar 

  18. • Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24. https://doi.org/10.1016/S0140-6736(16)32409-6. An early report from this study led to a change in the current standard of care to include combination therapy. Formal guideline revision was released (see citation 19).

    Article  CAS  PubMed  Google Scholar 

  19. Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35(20):2324–8. https://doi.org/10.1200/JCO.2017.72.4948.

    Article  PubMed  Google Scholar 

  20. Sinn M, et al. CONKO-005: adjuvant therapy in R0 resected pancreatic cancer patients with gemcitabine plus erlotibin versus gemcitabine for 24 weeks—a prospective randomized phase III study. J Clin Oncol. 2015;33(suppl; abstr 4007).

  21. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703. https://doi.org/10.1056/NEJMoa1304369.

    Article  Google Scholar 

  22. Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35(6):600–4. https://doi.org/10.1016/j.ejso.2008.12.006.

    Article  PubMed  Google Scholar 

  23. Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191(1):7–16. https://doi.org/10.1007/s00066-014-0737-7.

    Article  PubMed  Google Scholar 

  24. Youngwirth LM, Nussbaum DP, Thomas S, Adam MA, Blazer DG 3rd, Roman SA, et al. Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18 243 patients. J Surg Oncol. 2017;116:127–32. https://doi.org/10.1002/jso.24630.

    Article  CAS  PubMed  Google Scholar 

  25. Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230(6):776–82. discussion 82-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007;246(5):734–40. https://doi.org/10.1097/SLA.0b013e318156eef3.

    Article  PubMed  Google Scholar 

  27. Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299(9):1019–26. https://doi.org/10.1001/jama.299.9.1019.

  28. Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an eastern cooperative oncology group study. J Clin Oncol. 1998;16(1):317–23. https://doi.org/10.1200/JCO.1998.16.1.317.

    Article  CAS  PubMed  Google Scholar 

  29. Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496–502. https://doi.org/10.1200/JCO.2007.15.8634.

    Article  CAS  PubMed  Google Scholar 

  30. Varadhachary GR, Wolff RA, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487–95. https://doi.org/10.1200/JCO.2007.15.8642.

    Article  CAS  PubMed  Google Scholar 

  31. Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, et al. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014;89(4):830–8. https://doi.org/10.1016/j.ijrobp.2014.03.034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yovino S, Maidment BW 3rd, Herman JM, Pandya N, Goloubeva O, Wolfgang C, et al. Analysis of local control in patients receiving IMRT for resected pancreatic cancers. Int J Radiat Oncol Biol Phys. 2012;83(3):916–20. https://doi.org/10.1016/j.ijrobp.2011.08.026.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, 37212, USA

    Marc T. Roth & Jordan D. Berlin

  2. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Jordan D. Berlin

Authors
  1. Marc T. Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordan D. Berlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc T. Roth.

Ethics declarations

Conflict of Interest

Marc T. Roth declares that he has no conflict of interest.

Jordan D. Berlin has received compensation from Celgene, Genentech/Roche, AbbVie, Erytech, Armo, Rafael, EMD Serono/Merck KGA, Aduro, Gritstone, Vertex, BelGene, and AstraZeneca for participation on advisory boards, and has also received compensation from Celgene for participation on a steering committee and the APACT trial; has received non-financial support from Symphogen and Karyopharm for participation on advisory boards; and has participated in clinical trials supported by Incyte, EMD Serono/Merck KGA, Genentech, Taiho, AbbVie, FivePrime, Loxo, Symphogen, and Calithera.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Gastrointestinal Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roth, M.T., Berlin, J.D. Current Concepts in the Treatment of Resectable Pancreatic Cancer. Curr Oncol Rep 20, 39 (2018). https://doi.org/10.1007/s11912-018-0685-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-018-0685-y

Keywords

Search

Navigation