Impact of Tumor Grade on Prognosis in Pancreatic Cancer: Should We Include Grade in AJCC Staging?
AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication.
The Surveillance, Epidemiology, and End Results (SEER) database (1991–2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade.
For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31–1.48) as well as for stage I (HR 1.28, 95% CI 1.07–1.54), stage IIA (HR 1.43, 95% CI 1.26–1.61), stage IIB (HR 1.38, 95% CI 1.27–1.50), stage III (HR 1.28, 95% CI 1.02–1.59), and stage IV (HR 1.58, 95% CI 1.21–2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages.
Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials.
- Greene, FL, Sobin, LH (2008) The staging of cancer: a retrospective and prospective appraisal. CA Cancer J Clin. 58: pp. 180-190 CrossRef
- Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, et al., editors. American joint committee on cancer: AJCC cancer staging manual. 6th ed. New York, NY: Springer; 2002.
- Bilimoria, KY, Bentrem, DJ, Ko, CY, Ritchey, J, Stewart, AK, Winchester, DP (2007) Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer. 110: pp. 738-744 CrossRef
- Brennan, MF, Kattan, MW, Klimstra, D, Conlon, K (2004) Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas. Ann Surg. 240: pp. 293-298 CrossRef
- Ferrone, CR, Kattan, MW, Tomlinson, JS, Thayer, SP, Brennan, MF, Warshaw, AL (2005) Validation of a postresection pancreatic adenocarcinoma nomogram for disease-specific survival. J Clin Oncol. 23: pp. 7529-7535 CrossRef
- Geer, RJ, Brennan, MF (1993) Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 165: pp. 68-72 CrossRef
- Lim, JE, Chien, MW, Earle, CC (2003) Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 237: pp. 74-85 CrossRef
- Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006;10:1199–210.
- Benassai, G, Mastrorilli, M, Quarto, G, Cappiello, A, Giani, U, Forestieri, P (2000) Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas. J Surg Oncol. 73: pp. 212-218 CrossRef
- Gebhardt, C, Meyer, W, Reichel, M, Wünsch, PH (2000) Prognostic factors in the operative treatment of ductal pancreatic carcinoma. Langenbecks Arch Surg. 385: pp. 14-20 CrossRef
- Kuhlmann, KF, Castro, SM, Wesseling, JG, ten Kate, FJ, Offerhaus, GJ, Busch, OR (2004) Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer. 40: pp. 549-558 CrossRef
- Kumar, V, Fausto, N, Abbas, A (2004) Robbins and Cotran Pathologic Basis of Disease. Saunders, Philadelphia
- Havener, L (2004) Standards for Cancer Registries Volume III: Standards for Completeness, Quality, Analysis, and Management of Data. North American Association of Central Cancer Registries, Springfield, IL
- Surveillance, Epidemiology, and End Results (SEER) Program. Public use data (1973–2005). National Cancer Institute. http://www.seer.cancer.gov. Accessed October 2008.
- Schwarz, RE, Smith, DD (2006) Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database. Ann Surg Oncol. 13: pp. 1189-1200 CrossRef
- Tomlinson, JS, Jain, S, Bentrem, DJ, Sekeris, EG, Maggard, MA, Hines, OJ (2007) Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 142: pp. 767-773 CrossRef
- Takai, S, Satoi, S, Toyokawa, H, Yanagimoto, H, Sugimoto, N, Tsuji, K (2003) Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: a retrospective, single-institution experience. Pancreas. 26: pp. 243-249 CrossRef
- Sperti, C, Pasquali, C, Piccoli, A, Pedrazzoli, S (1996) Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 83: pp. 625-631 CrossRef
- Kedra, B, Popiela, T, Sierzega, M, Precht, A (2001) Prognostic factors of long-term survival after resective procedures for pancreatic cancer. Hepatogastroenterology. 48: pp. 1762-1766
- Nitecki, SS, Sarr, MG, Colby, TV, Heerden, JA (1995) Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?. Ann Surg 221: pp. 59-66 CrossRef
- Raut, CP, Tseng, JF, Sun, CC, Wang, H, Wolff, RA, Crane, CH (2007) Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 246: pp. 52-60 CrossRef
- Lightner, AM, Glasgow, RE, Jordan, TH, Krassner, AD, Way, LW, Mulvihill, SJ (2004) Pancreatic resection in the elderly. J Am Coll Surg. 198: pp. 697-706 CrossRef
- Finlayson, E, Fan, Z, Birkmeyer, JD (2007) Outcomes in octogenarians undergoing high-risk cancer operation: a national study. J Am Coll Surg. 205: pp. 729-734 CrossRef
- Oettle, H, Post, S, Neuhaus, P, Gellert, K, Langrehr, J, Ridwelski, K (2007) Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 297: pp. 267-277 CrossRef
- Neoptolemos, JP, Stocken, DD, Friess, H, Bassi, C, Dunn, JA, Hickey, H (2004) European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 350: pp. 1200-1210 CrossRef
- Picozzi, VJ, Pisters, PW, Vickers, SM, Strasberg, SM (2008) Strength of the evidence: adjuvant therapy for resected pancreatic cancer. J Gastrointest Surg. 12: pp. 657-661 CrossRef
- Adsay, NV, Basturk, O, Bonnett, M, Kilinc, N, Andea, AA, Feng, J (2005) A proposal for a new and more practical grading scheme for pancreatic ductal adenocarcinoma. Am J Surg Pathol. 29: pp. 724-733 CrossRef
- Eltoum, IA, Eloubeidi, MA, Chhieng, DC, Tamhane, A, Crowe, R, Jhala, D (2005) Cytologic grade independently predicts survival of patients with pancreatic adenocarcinoma. Am J Clin Pathol. 124: pp. 697-707 CrossRef
- Impact of Tumor Grade on Prognosis in Pancreatic Cancer: Should We Include Grade in AJCC Staging?
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Annals of Surgical Oncology
Volume 17, Issue 9 , pp 2312-2320
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA, USA
- 2. Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- 3. Department of Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA
- 4. Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- 5. Division of Hematology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA