Pancreatic Cancer pp 1093-1108 | Cite as

Neoadjuvant Treatment in Pancreatic Cancer

  • Alysandra Lal
  • Douglas B. Evans
Reference work entry


Neoadjuvant chemoradiation is a logical approach to the treatment of pancreatic cancer given its aggressive course and high likelihood for being metastatic at the time of diagnosis. A surgery-last (neoadjuvant) approach may confer the advantages of decreased toxicity (patients are not in the postoperative recovery phase of their illness) and increased efficacy (systemic therapy not delayed) as compared with adjuvant treatment given following a large operation. Further, because patients with progressive disease may be identified prior to operation, neoadjuvant therapy offers the benefit of improved patient selection for pancreaticoduodenectomy (PD). In patients with borderline resectable disease in whom surgery may be possible (but is not an attractive initial option), neoadjuvant therapy may increase the chance of a margin negative resection by sterilizing the tumor cells at the periphery of the tumor even in the absence of a partial or complete radiographic response. The critical components of successful neoadjuvant treatment sequencing for pancreatic cancer include a clear definition of resectability (and unresectability) based on accurate radiographic staging, the ability to achieve a tissue diagnosis of cancer, and means to safely decompress the biliary system when necessary.

There have been at least 13 prospective trials evaluating the role of neoadjuvant treatment for localized (T1-T3) pancreatic adenocarcinoma. Two of the largest and most recent trials evaluated gemcitabine, with or without cisplatin, and rapid fraction radiation therapy; 66–74% of patients ultimately underwent pancreaticoduodenectomy. Positive resection margins were uncommon and the median survival for patients who completed all treatment to include resection of the primary tumor was 31–34 months. This encouraging data has provided initial evidence in support of a neoadjuvant gemcitabine-based treatment strategy for patients with localized, potentially resectable pancreatic adenocarcinoma.

Patients with borderline resectable disease are particularly well suited to neoadjuvant treatment sequencing, although no standardized treatment strategy has been identified. When the operation is more difficult and potentially of even higher risk, and the risk for recurrence is also increased, a surgery last strategy is appealing in order to exclude those patients from surgery who are demonstrated to have progressive disease or evolving medical comorbidities which a neoadjuvant treatment strategy may expose. Many studies have been done in patients with locally advanced disease but only recently has the category of borderline resectable disease been accurately defined. The value of accurate pretreatment staging and multidisciplinary care is now becoming apparent to clinicians of all specialties. However, for this to be possible, all members of the multidisciplinary team must agree on the definitions used to stage patients radiographically because treatment is stage specific.


Pancreatic Cancer Improve Patient Selection Resectable Pancreatic Adenocarcinoma Borderline Resectable Disease Borderline Resectable Tumor 
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  1. 1.
    Katz MH, Pisters PW, Evans DB, et al.: Borderline resectable pancreatic cancer: The importance of this emerging stage of disease. J Am Coll Surg. 2008;206(5):833–846; discussion 846–848.Google Scholar
  2. 2.
    Tseng JF, Raut CP, Lee JE, et al.: Pancreaticoduodenectomy with vascular resection: Margin status and survival duration. J Gastrointest Surg 2004;8(8):935–49, discussion 949–950.CrossRefPubMedGoogle Scholar
  3. 3.
    Gastrointestinal Tumor Study Group. Radiation therapy combined with adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Cancer 1985;56(11):2563–2568.Google Scholar
  4. 4.
    Heinrich S, Schafer M, Weber A, et al.: Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: Results of a prospective phase II trial. Ann Surg 2008;248(6):1014–1022.CrossRefPubMedGoogle Scholar
  5. 5.
    Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350(12):1200–1210.CrossRefPubMedGoogle Scholar
  6. 6.
    Breslin TM, Hess KR, Harbison DB, et al.: Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: Treatment variables and survival duration. Ann Surg Oncol 2001;8(2):123–132.CrossRefPubMedGoogle Scholar
  7. 7.
    Crane CH, Varadhachary G, Wolff RA, Pisters PW, Evans DB. The argument for pre-operative chemoradiation for localized, radiographically resectable pancreatic cancer. Best Pract Res Clin Gastroenterol 2006;20(2):365–382.CrossRefPubMedGoogle Scholar
  8. 8.
    Lowy AM, Lee JE, Pisters PW, et al.: Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg 1997;226(5):632–641.CrossRefPubMedGoogle Scholar
  9. 9.
    Sohn TA, Yeo CJ, Cameron JL, et al.: Resected adenocarcinoma of the pancreas-616 patients: Results, outcomes, and prognostic indicators. J Gastrointest Surg 2000;4(6):567–579.CrossRefPubMedGoogle Scholar
  10. 10.
    Raut CP, Evans DB, Crane CH, Pisters PW, Wolff RA. Neoadjuvant therapy for resectable pancreatic cancer. Surg Oncol Clin N Am 2004;13(4):639–61, ix.CrossRefPubMedGoogle Scholar
  11. 11.
    Pisters PW, Abbruzzese JL, Janjan NA, et al.: Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 1998;16(12):3843–3850.PubMedGoogle Scholar
  12. 12.
    Pisters PW, Wolff RA, Janjan NA, et al.: Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: Toxicities, histologic response rates, and event-free outcome. J Clin Oncol 2002;20(10):2537–2544.CrossRefPubMedGoogle Scholar
  13. 13.
    Varadhachary GR, Wolff RA, Crane CH, et al.: Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008;26(21):3487–3495.CrossRefPubMedGoogle Scholar
  14. 14.
    Evans DB, Varadhachary GR, Crane CH, et al.: Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008;26(21):3496–3502.CrossRefPubMedGoogle Scholar
  15. 15.
    Varadhachary GR, Tamm EP, Abbruzzese JL, et al.: Borderline resectable pancreatic cancer: Definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13(8):1035–1046.CrossRefPubMedGoogle Scholar
  16. 16.
    Katz MH, Pisters PW, Evans DB, et al.: Borderline resectable pancreatic cancer: The importance of this emerging stage of disease. J Am Coll Surg 2008;206(5):833–846, discussion 846–848.CrossRefPubMedGoogle Scholar
  17. 17.
    Winter JM, Cameron JL, Campbell KA, et al.: 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 2006;10(9):1199–1210, discussion 1210–1211.CrossRefPubMedGoogle Scholar
  18. 18.
    Takai S, Satoi S, Toyokawa H, et al.: Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: A retrospective, single-institution experience. Pancreas 2003;26(3):243–249.CrossRefPubMedGoogle Scholar
  19. 19.
    Richter A, Niedergethmann M, Sturm JW, Lorenz D, Post S, Trede M. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience. World J Surg 2003;27(3):324–329.CrossRefPubMedGoogle Scholar
  20. 20.
    Kuhlmann KF, de Castro SM, Wesseling JG, et al.: Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer 2004;40(4):549–558.CrossRefPubMedGoogle Scholar
  21. 21.
    Westgaard A, Tafjord S, Farstad IN, et al.: Resectable adenocarcinomas in the pancreatic head: The retroperitoneal resection margin is an independent prognostic factor. BMC Cancer 2008;8:5.CrossRefPubMedGoogle Scholar
  22. 22.
    Fusai G, Warnaar N, Sabin CA, Archibong S, Davidson BR. Outcome of R1 resection in patients undergoing pancreatico-duodenectomy for pancreatic cancer. Eur J Surg Oncol 2008;34(12):1309–1315.PubMedGoogle Scholar
  23. 23.
    Butturini G, Stocken DD, Wente MN, et al.: Influence of resection margins and treatment on survival in patients with pancreatic cancer: Meta-analysis of randomized controlled trials. Arch Surg 2008;143(1):75–83, discussion 83.CrossRefPubMedGoogle Scholar
  24. 24.
    Verbeke CS. Resection margins and R1 rates in pancreatic cancer–are we there yet? Histopathology 2008;52(7):787–796.CrossRefPubMedGoogle Scholar
  25. 25.
    Jessup JM, Steele G,Jr, Mayer RJ, Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg 1993;128(5):559–564.PubMedGoogle Scholar
  26. 26.
    White R, Lee C, Anscher M, et al.: Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol 1999;6(1):38–45.CrossRefPubMedGoogle Scholar
  27. 27.
    Todd KE, Gloor B, Lane JS, Isacoff WH, Reber HA. Resection of locally advanced pancreatic cancer after downstaging with continuous-infusion 5-fluorouracil, mitomycin-C, leucovorin, and dipyridamole. J Gastrointest Surg 1998;2(2):159–166.CrossRefPubMedGoogle Scholar
  28. 28.
    Mehta VK, Fisher G, Ford JA, et al.: Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg 2001;5(1):27–35.CrossRefPubMedGoogle Scholar
  29. 29.
    Evans DB, Rich TA, Byrd DR, et al.: Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 1992;127(11):1335–1339.PubMedGoogle Scholar
  30. 30.
    Pendurthi TK, Hoffman JP, Ross E, Johnson DE, Eisenberg BL. Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma. Am Surg 1998;64(7):686–692.PubMedGoogle Scholar
  31. 31.
    Spitz FR, Abbruzzese JL, Lee JE, et al.: Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 1997;15(3):928–937.PubMedGoogle Scholar
  32. 32.
    Aloia TE, Lee JE, Vauthey JN, et al.: Delayed Recovery after Pancreaticoduodenectomy: A Major Factor lmpairing the Delivery of Adjuvant Therapy? J Amer Col Surg 2007;204(3):347–355.Google Scholar
  33. 33.
    Corsini MM, Miller RC, Haddock MG, et al.: Adjuvant Radiotherapy and Chemotherapy for Pancreatic Carcinoma: The Mayo Clinic Experience (1975–2005). J Clin Oncol 2008;26:3511–3516.Google Scholar
  34. 34.
    Herman JM, Swartz MJ, HSU CC, et al.: Analysis of Fluorouracil-Based Adjuvant Chemotherapy and Radiation After Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas: Results of a Large, Prospectively Collected Database at the Johns Hopkins Hospital. J Clin Oncol 2008;26:3503–3510.Google Scholar
  35. 35.
    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):317–323.PubMedGoogle Scholar
  36. 36.
    Sasson AR, Wetherington RW, Hoffman JP, et al.: Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: Analysis of histopathology and outcome. Int J Gastrointest Cancer 2003;34(2–3):121–128.CrossRefPubMedGoogle Scholar
  37. 37.
    Wolff RA, Evans DB, Gravel DM, et al.: Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res 2001;7(8):2246–2253.PubMedGoogle Scholar
  38. 38.
    Magnin V, Moutardier V, Giovannini MH, et al.: Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer. Int J Radiat Oncol Biol Phys 2003;55(5):1300–1304.CrossRefPubMedGoogle Scholar
  39. 39.
    Calvo FA, Matute R, Garcia-Sabrido JL, et al.: Neoadjuvant chemoradiation with tegafur in cancer of the pancreas: Initial analysis of clinical tolerance and outcome. Am J Clin Oncol 2004;27(4):343–349.CrossRefPubMedGoogle Scholar
  40. 40.
    Talamonti MS, Small W,Jr, Mulcahy MF, et al.: A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13(2):150–158.CrossRefPubMedGoogle Scholar
  41. 41.
    Pisters PW, Hudec WA, Hess KR, et al.: Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg 2001;234(1):47–55.CrossRefPubMedGoogle Scholar
  42. 42.
    Davids PH, Groen AK, Rauws EA, Tytgat GN, Huibregtse K. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992;340(8834–8835):1488–1492.CrossRefPubMedGoogle Scholar
  43. 43.
    Kaassis M, Boyer J, Dumas R, et al.: Plastic or metal stents for malignant stricture of the common bile duct? results of a randomized prospective study. Gastrointest Endosc 2003;57(2):178–182.CrossRefPubMedGoogle Scholar
  44. 44.
    Evans DB, Crane CH, Charnsangavej C, Wolff RA. The added value of multidisciplinary care for patients with pancreatic cancer. Ann Surg Oncol 2008;15(8):2078–2080.CrossRefPubMedGoogle Scholar
  45. 45.
    Pawlik TM, Laheru D, Hruban RH, et al.: Evaluating the impact of a single-day multidisciplinary clinic on the management of pancreatic cancer. Ann Surg Oncol 2008;15(8):2081–2088.CrossRefPubMedGoogle Scholar
  46. 46.
    Mornex F, Girard N, Scoazec JY, et al.: Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: The french SFRO-FFCD 97–04 phase II trial. Int J Radiat Oncol Biol Phys 2006;65(5):1471–1478.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Alysandra Lal
    • 1
  • Douglas B. Evans
    • 1
  1. 1.Department of SurgeryThe Medical College of WisconsinMilwaukeeUSA

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