Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Current management of locally advanced pancreatic cancer

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 356–364 (2005)Cite this article

Abstract

Almost 30% of patients with pancreatic cancer present with large, locally advanced tumors in the absence of distant metastases. Because surgical resection is frequently contraindicated by vascular invasion, locally advanced pancreatic cancer has a dismal prognosis with a 6–10-month median survival. Recent advances in the multimodality treatment of other gastrointestinal malignancies have not altered the management of patients with locally advanced pancreatic cancer, a clinical dilemma reflected by the number of nonrandomized trials and anecdotal reports addressing this difficult disease. Our review summarizes the current status of aggressive surgical resection and neoadjuvant chemoradiation for locally advanced pancreatic cancer and suggests a treatment algorithm for patients with this disease based upon published clinical evidence.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: CT scan images of patients with locally advanced pancreatic cancer.

Similar content being viewed by others

References

  1. American Cancer Society (2004) Cancer facts and figures. Atlanta: American Cancer Society

  2. National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) (online April 2005) SEER*Stat 6.1 Database: Incidence—SEER 9 Regs Public-Use, Nov 2004 Sub (1973-2002). [http://www.seer.cancer.gov/seerstat/] (accessed 5 July 2005)

  3. Haller DG (2003) Chemotherapy for advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 56 (Suppl): S16–S23

    Article  Google Scholar 

  4. Fortner JG (1973) Regional resection of cancer of the pancreas: a new surgical approach. Surgery 73: 307–320

    CAS  PubMed  Google Scholar 

  5. Lillemoe KD et al. (1996) Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer? Ann Surg 223: 718–725

    Article  CAS  Google Scholar 

  6. Sohn TA et al. (2000) Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4: 567–579

    Article  CAS  Google Scholar 

  7. Nakao A et al. (2004) Extended radical resection versus standard resection for pancreatic cancer: the rationale for extended radical resection. Pancreas 28: 289–292

    Article  Google Scholar 

  8. Shoup M et al. (2004) Is there a role for staging laparoscopy in patients with locally advanced, unresectable pancreatic adenocarcinoma? J Gastrointest Surg 8: 1068–1071

    Article  Google Scholar 

  9. Liu RC and Traverso LW (2005) Diagnostic laparoscopy improves staging of pancreatic cancer deemed locally unresectable by Computed Tomography. Surg Endosc 19: 638–642

    Article  CAS  Google Scholar 

  10. Crile G Jr (1970) The advantages of bypass operations over radical pancreatoduodenectomy in the treatment of pancreatic carcinoma. Surg Gynecol Obstet 130: 1049–1053

    PubMed  Google Scholar 

  11. Neoptolemos JP et al. (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350: 1200–1210

    Article  CAS  Google Scholar 

  12. Benassai G et al. (2000) Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas. J Surg Oncol 73: 212–218

    Article  CAS  Google Scholar 

  13. Kayahara M et al. (1995) Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion. Surgery 117: 616–623

    Article  CAS  Google Scholar 

  14. Fortner JG et al. (1996) Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg 223: 147–153

    Article  CAS  Google Scholar 

  15. Howard TJ et al. (2003) Efficacy of venous reconstruction in patients with adenocarcinoma of the pancreatic head. J Gastrointest Surg 7: 1089–1095

    Article  Google Scholar 

  16. Leach SD et al. (1998) Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head. Br J Surg 85: 611–617

    Article  CAS  Google Scholar 

  17. Roder JD et al. (1996) Carcinoma of the periampullary region: who benefits from portal vein resection? Am J Surg 171: 170–174

    Article  CAS  Google Scholar 

  18. Bachellier P et al. (2001) Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile? Am J Surg 182: 120–129

    Article  CAS  Google Scholar 

  19. Sasson AR et al. (2002) En bloc resection for locally advanced cancer of the pancreas: is it worthwhile? J Gastrointest Surg 6: 147–157

    Article  Google Scholar 

  20. Nakao A (2003) Debate: extended resection for pancreatic cancer; the affirmative case. J Hepatobiliary Pancreat Surg 10: 57–60

    PubMed  Google Scholar 

  21. Tseng JF et al. (2004) Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 8: 935–949

    Article  Google Scholar 

  22. Poon RT et al. (2004) Pancreaticoduodenectomy with en bloc portal vein resection for pancreatic carcinoma with suspected portal vein involvement. World J Surg 28: 602–608

    Article  Google Scholar 

  23. Nakagohri T et al. (2003) Survival benefits of portal vein resection for pancreatic cancer. Am J Surg 186: 149–153

    Article  Google Scholar 

  24. Launois B et al. (1999) Who benefits from portal vein resection during pancreaticoduodenectomy for pancreatic cancer? World J Surg 23: 926–929

    Article  CAS  Google Scholar 

  25. Pedrazzoli S et al. (1998) Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 228: 508–517

    Article  CAS  Google Scholar 

  26. Yeo CJ et al. (2002) Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 236: 355–366

    Article  Google Scholar 

  27. Beger HG et al. (2003) Treatment of pancreatic cancer: challenge of the facts. World J Surg 27: 1075–1084

    Article  Google Scholar 

  28. Yeo CJ et al. (1997) Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225: 621–633

    Article  CAS  Google Scholar 

  29. Spitz FR et al. (1997) Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 15: 928–937

    Article  CAS  Google Scholar 

  30. Klinkenbijl JH et al. (1999) 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 230: 776–782

    Article  CAS  Google Scholar 

  31. Kim HJ et al. (2002) Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 6: 763–769

    Article  Google Scholar 

  32. Pisters PW et al. (1998) Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 16: 3843–3850

    Article  CAS  Google Scholar 

  33. Moertel CG et al. (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48: 1705–1710

    Article  CAS  Google Scholar 

  34. Burris HA III et al. (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403–2413

    Article  CAS  Google Scholar 

  35. Ikeda M et al. (2002) A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Br J Cancer 86: 1551–1554

    Article  CAS  Google Scholar 

  36. Li CP et al. (2003) Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 57: 98–104

    Article  CAS  Google Scholar 

  37. Klaassen DJ et al. (1985) Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil—an Eastern Cooperative Oncology Group study. J Clin Oncol 3: 373–378

    Article  CAS  Google Scholar 

  38. Fisher BJ et al. (1999) Analysis of the clinical benefit of 5-fluorouracil and radiation treatment in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 45: 291–295

    Article  CAS  Google Scholar 

  39. Van Cutsem E et al. (2004) Systemic treatment of pancreatic cancer. Eur J Gastroenterol Hepatol 16: 265–274

    Article  CAS  Google Scholar 

  40. Moore MJ et al. (2003) Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 21: 3296–3302

    Article  CAS  Google Scholar 

  41. Van Cutsem E et al. (2004) Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 22: 1430–1438

    Article  CAS  Google Scholar 

  42. Rocha Lima CM et al. (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22: 3776–3783

    Article  CAS  Google Scholar 

  43. Moore M et al. (2005) Erlotinib improves survival when added to gemcitabine in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). 2005 Gastrointestinal Cancer Symposium Program/Proceedings [abstract #77]: a121

    Google Scholar 

  44. Maheshwari V et al. (2005) Phase I study of celecoxib, irinotecan, and concurrent radiotherapy in the preoperative treatment of locally-advanced pancreatic cancer [abstract #109]. 2005 Gastrointestinal Cancer Symposium Program/Proceedings

    Google Scholar 

  45. Crane CH et al. (2003) Initial experience combining cyclooxygenase-2 inhibition with chemoradiation for locally advanced pancreatic cancer. Am J Clin Oncol 26: S81–S84

    Article  Google Scholar 

  46. Singh SM et al. (1990) Surgical palliation for pancreatic cancer. The UCLA experience. Ann Surg 212: 132–139

    Article  CAS  Google Scholar 

  47. Nieveen van Dijkum EJ et al. (2005) Quality of life after curative or palliative surgical treatment of pancreatic and periampullary carcinoma. Br J Surg 92: 471–477

    Article  CAS  Google Scholar 

  48. Ammori JB et al. (2003) Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas. J Gastrointest Surg 7: 766–772

    Article  Google Scholar 

  49. Fogelman DR et al. (2004) The evolution of adjuvant and neoadjuvant chemotherapy and radiation for advanced pancreatic cancer: from 5-fluorouracil to GTX. Surg Oncol Clin N Am 13: 711–735, x

    Article  Google Scholar 

  50. Aristu J et al. (2003) Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol 26: 30–36

    Article  Google Scholar 

  51. Wilkowski R et al. (2004) Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer. World J Surg 28: 1011–1018

    Article  Google Scholar 

  52. Talamonti MS et al. (2000) Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity. J Clin Oncol 18: 3384–3389

    Article  CAS  Google Scholar 

  53. Safran H et al. (2001) Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 49: 1275–1279

    Article  CAS  Google Scholar 

  54. Epelbaum R et al. (2002) Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol 81: 138–143

    Article  CAS  Google Scholar 

  55. Blackstock AW et al. (2003) Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas. Int J Gastrointest Cancer 34: 107–116

    Article  CAS  Google Scholar 

  56. Viret F et al. (2003) Docetaxel and radiotherapy and pancreatic cancer. Pancreas 27: 214–219

    Article  CAS  Google Scholar 

  57. Brunner TB et al. (2003) Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 55: 144–153

    Article  CAS  Google Scholar 

  58. Okusaka T et al. (2004) Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. Br J Cancer 91: 673–677

    Article  CAS  Google Scholar 

  59. Rich T et al. (2004) Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol 27: 51–56

    Article  CAS  Google Scholar 

Download references

Acknowledgements

AJM receives funding from the NIH (DK60485) and the Competitive Medical Research Foundation of the University of Pittsburgh School of Medicine, PA, USA.

Author information

Authors and Affiliations

  1. Division of Surgical Oncology at the Beth Israel Medical Center, New York, NY, USA

    Vivek Maheshwari

  2. Albert Einstein Medical Center, New York, NY, USA

    Vivek Maheshwari

  3. Assistant Professor of Surgery, Cell Biology, and Physiology in the Division of Surgical Oncology at the University of Pittsburgh Cancer Institute, PA, USA

    A James Moser

Authors
  1. Vivek Maheshwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A James Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A James Moser.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Glossary

ADJUVANT TREATMENT

Treatment given to patients after surgical resection

NEOADJUVANT THERAPY

Treatment given to unresected patients

CLINICAL BENEFIT RESPONSE INDEX

A composite measure of pain (pain intensity and analgesic consumption), Karnofsky performance status and body weight

3-DIMENSIONAL CONFORMAL RADIOTHERAPY

A technique that conforms the spatial distribution of the high radiation dose to the shape of the tumor while decreasing the volume of normal surrounding tissue exposed

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maheshwari, V., Moser, A. Current management of locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2, 356–364 (2005). https://doi.org/10.1038/ncpgasthep0240

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpgasthep0240

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing