Abstract
Pancreatic adenocarcinoma still ranks high among cancer-related deaths worldwide. In spite of substantial strides in preoperative staging, surgery, perioperative care, and adjuvant treatment, the survival still remains dismal. A number of patient-, disease-, and surgeon-related factors play a role in deciding the eventual outcome of the patient. The aim of this commentary is to review the current knowledge of various factors and the recent advances that impact the survival of patients with pancreatic adenocarcinoma. A search of scientific literature using Embase and MEDLINE, for the years 1985–2015, was carried out for search terms “pancreatic cancer” and “survival.” Further search was based on the various specific prognostic factors that contribute towards survival of patients with pancreatic cancer found in the literature. Most of the studies used for this review include those that deal with pancreatic head cancers, some include patients with pancreatic cancers in all locations while very few included patients with tumors of body and tail only. In spite of significant developments in pre- and perioperative management, increased rates of margin-negative resections, and use of adjuvant treatment, the survival rates of pancreatic cancer patients remains poor. A paradigm shift with more effective adjuvant regimen and genetic interventions may help change the outcomes of patients with pancreatic cancer.
Similar content being viewed by others
References
Perysinakis I, Avlonitis S, Georgiadou D (2015) Five-year actual survival after pancreatoduodenectomy for pancreatic head cancer. ANZ J Surg 85(3):183–186
Millikan KW, Deziel DJ, Silverstein JC et al (1999) Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg 65:618–623, discussion 23–4
Cameron JL, Pitt HA, Yeo CJ et al (1993) One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg 217:430–435, discussion 5–8
Schnelldorfer T, Ware AL, Sarr MG et al (2008) Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg 247:456–462
Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69
Hariharan D, Saied A, Kocher HM (2008) Analysis of mortality rates for pancreatic cancer across the world. HPB (Oxford) 10:58
Ries LA, Eisner MP, Kosary CL et al (2000) SEER cancer statistics review, 1973–1996. National Cancer Institute, Bethesda
Nitecki SS, Sarr MG, Colby TV et al (1995) Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg 221(1):59–66
Winter JM, Brennan MF, Tang LH et al (2012) Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol 19:169–175
Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210
Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277
Begg CB, Cramer LD, Hoskins WJ et al (1998) Impact of hospital volume on operative mortality for major cancer surgery. JAMA 280:1747–1751
Winter JM, Cameron JL, Campbell KA et al (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg 10:1199–1210
Grobmyer SR, Pieracci FM, Allen PJ et al (2007) Defining morbidity after pancreaticoduodenectomy: use of a prospective complication grading system. J Am Coll Surg 204:356–364
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 237:74
Conlon KC, Klimstra DS, Brennan MF (1996) Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223:273–279
Trede M, Richter A, Wendl K (2001) Personal observations, opinions, and approaches to cancer of the pancreas and the periampullary area. Surg Clin N Am 81:595–610
Yeo CJ, Cameron JL, Lillemoe KD et al (1995) Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221:721–731, discussion 31–3
Allison DC, Piantadosi S, Hruban RH et al (1998) DNA content and other factors associated with ten-year survival after resection of pancreatic carcinoma. J Surg Oncol 67:151–159
Riall TS, Cameron JL, Lillemoe KD et al (2006) Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery 140:764–772
Hoffman JP, Lipsitz S, Pisansky T et al (1998) 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 16:317
Staley CA, Lee JE, Cleary KR et al (1996) Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am J Surg 171:118
Pisters PW, Abbruzzese JL, Janjan NA et al (1998) Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 16:3843
Pisters PW, Wolff RA, Janjan NA et al (2002) Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol 20:2537
Assifi MM, Lu X, Eibl G et al (2011) Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery 150:466
Andriulli A, Festa V, Botteri E et al (2012) Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol 19:1644
Gillen S, Schuster T, Meyer Zum Büschenfelde C et al (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7, e1000267
Varadhachary GR, Tamm EP, Abbruzzese JL et al (2006) Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 13(8):1035–1046, Epub 2006 Jul 24
Lopez NE, Prendergast C, Lowy AM (2014) Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol 20(31):10740–10751
Katz MH, Pisters PW, Evans DB et al (2008) Borderline resectable pancreatic cancer the importance of this emerging stage of disease. J Am Coll Surg 206(5):833–846, discussion 846–8
Callery MP, Chang KJ, Fishman EK et al (2009) Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 16:1727
NCCN National Comprehensive Cancer Network (NCCN) guidelines. Available at: www.nccn.org
Wolff RA, Abbruzzese JL, Evans DB. Neoplasms of the exocrine pancreas.In: Bast RC Jr, Kufe DW, Pollock RE, et al., eds.Cancer Medicine.6th ed.Hamilton, Ontario, Canada: American Cancer Society + BC Decker Inc, 2003: 1585614
Li D, Xie K, Wolff RA et al (2004) Pancreatic cancer. Lancet 363(9414):1049–1057
Greer SE, Pipas JM, Sutton JE et al (2008) Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma. J Am Coll Surg 206:451
Stokes JB, Nolan NJ, Stelow EB et al (2011) Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 18:619
Ammori JB, Colletti LM, Zalupski MM 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
Pipas JM, Barth RJ Jr, Zaki B et al (2005) Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol 12:995
Palmer DH, Stocken DD, Hewitt H et al (2007) A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol 14:2088
Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899–903
Kosuge T, Kiuchi T, Mukai K, Kakizoe T, Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer (JSAP) (2006) A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol 36:159–165
Smeenk HG, van Eijck CH, Hop WC et al (2007) 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 246:734–740
Takada T, Amano H, Yasuda H, Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract et al (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95:1685–1695
Neoptolemos JP, Stocken DD, Bassi C et al (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073
Uesaka K, Fukutomi A, Boku N, et al (2012) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study) (abstract). J Clin Oncol 30:(suppl 34; abstr 145)
Neoptolemos JP, Dunn JA, Stocken DD et al (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358:1576
Klinkenbijl JH, Jeekel J, Sahmoud T 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
Sindelar WF, Kinsella TJ (1999) Studies of intraoperative radiotherapy in carcinoma of the pancreas. Ann Oncol 10(Suppl 4):226
Hishinuma S, Ogata Y, Matsui J, Ozawa I (1998) Results of surgery and adjuvant radiotherapy for pancreatic cancer. J Hepatobiliary Pancreat Surg 5:143
Hosotani R, Kogire M, Arii S et al (1997) Results of pancreatectomy with radiation therapy for pancreatic cancer. Hepatogastroenterology 44:1528
Seufferlein T, Bachet JB, Van Cutsem E et al (2012) Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii33
Karpoff HM, Klimstra DS, Brennan MF, Conlon KC (2001) Results of total pancreatectomy for adenocarcinoma of the pancreas. Arch Surg 136:44
Dresler CM, Fortner JG, McDermott K, Bajorunas DR (1991) Metabolic consequences of (regional) total pancreatectomy. Ann Surg 214:131
Brooks JR, Brooks DC, Levine JD (1989) Total pancreatectomy for ductal cell carcinoma of the pancreas. An update. Ann Surg 209:405
Kneuertz PJ, Pitt HA, Bilimoria KY et al (2012) Risk of morbidity and mortality following hepato-pancreato-biliary surgery. J Gastrointest Surg 16:1727
Reddy S, Wolfgang CL, Cameron JL et al (2009) Total pancreatectomy for pancreatic adenocarcinoma: evaluation of morbidity and long-term survival. Ann Surg 250:282
Nathan H, Wolfgang CL, Edil BH et al (2009) Peri-operative mortality and long-term survival after total pancreatectomy for pancreatic adenocarcinoma: a population-based perspective. J Surg Oncol 99:87
Kalser MH, Barkin J, MacIntyre JM (1985) Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 56:397–402
Benassai G, Mastrorilli M, Mosella F, Mosella G (1999) Significance of lymph node metastases in the surgical management of pancreatic head carcinoma. J Exp Clin Cancer Res 18:23–28
Cameron JL, Riall TS, Coleman J, Belcher KA (2006) One thousand consecutive pancreaticoduodenectomies. Ann Surg 244:10–15
Ferrone CR, Kattan MW, Tomlinson JS et al (2005) Validation of a postresection pancreatic adenocarcinoma nomogram for disease-specific survival. J Clin Oncol 23:7529
Tomlinson JS, Jain S, Bentrem DJ et al (2007) Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg 142:767.79
Ishikawa O, Ohhigashi H, Sasaki Y et al (1988) Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head. Ann Surg 208:215
Tsuchiya R, Tsunoda T, Yamaguchi T (1990) Operation of choice for resectable carcinoma of the head of the pancreas. Int J Pancreatol 6:295
Stojadinovic A, Brooks A, Hoos A et al (2003) An evidence-based approach to the surgical management of resectable pancreatic adenocarcinoma. J Am Coll Surg 196:954
Manabe T, Ohshio G, Baba N et al (1989) Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Cancer 64:1132–1137
Satake K, Nishiwaki H, Yokomatsu H et al (1992) Surgical curability and prognosis for standard versus extended resection for T1 carcinoma of the pancreas. Surg Gynecol Obstet 175:259–265
Kawarada Y, Yokoi H, Isaji S et al (1999) Modified standard pancreaticoduodenectomy for the treatment of pancreatic head cancer. Digestion 60(Suppl 1):120–125
Nagakawa T (1996) Pancreaticoduodenectomy Geka Shinryo 38:437–444
Hanyu F, Imaizumi T, Nakasako T et al (1995) Pancreatic cancer. Gastroenterol Surg 18:323–330
Pedrazzoli S, DiCarlo V, Dionigi R 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
Yeo CJ, Cameron JL, Lillemoe KD 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
Farnell MB, Pearson RK, Sarr MG et al (2005) A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery 138:618
Chua TC, Saxena A (2010) Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg 14(9):1442–1452
Fortner JG (1973) Regional resection of cancer of the pancreas: a new surgical approach. Surgery 73:307–320
Leach SD, Lee JE, Charnsangavej C 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
Fuhrman GM, Leach SD, Staley CA et al (1996) Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group. Ann Surg 223:154
Murakami Y, Uemura K, Sudo T et al (2013) Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma. J Surg Oncol 107:414
Tseng JF, Raut CP, Lee JE et al (2004) Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 8:935
Raut CP, Tseng JF, Sun CC et al (2007) Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg 246:52
Martin RC 2nd, Scoggins CR, Egnatashvili V et al (2009) Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 144:154
Ramacciato G, Mercantini P, Petrucciani N et al (2009) Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma? Ann Surg Oncol 16:817
Castleberry AW, White RR, De La Fuente SG et al (2012) The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Ann Surg Oncol 19:4068
Nakagohri T, Kinoshita T, Konishi M et al (2003) Survival benefits of portal vein resection for pancreatic cancer. Am J Surg 186(2):149–153
Evans DB, Farnell MB, Lillemoe KD et al (2009) Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 16:1736
Martin RCG 2nd, Scoggins CR, Egnatashvili V et al (2009) Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 144:154–159
Yekebas EF, Bogoevski D, Cataldegirmen G et al (2008) En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and longterm survival in 136 patients. Ann Surg 247:300–309
Stitzenberg KB, Watson JC, Roberts A et al (2008) Survival after pancreatectomy with major arterial resection and reconstruction. Ann Surg Oncol 15:1399–1406
Mollberg N, Rahbari NN, Koch M et al (2011) Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg 254(6):882–893
Sosa JA, Bowman HM, Gordon TA et al (1998) Importance of hospital volume in the overall management of pancreatic cancer. Ann Surg 228(3):429–438
Lieberman MD, Kilbum H, Lindsey M et al (1995) Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancy. Ann Surg 222(5):638–645
Glasgow RE, Mulvihill SJ (1996) Relation of hospital volume to outcome in patients undergoing Whipple resection for adenocarcinoma in Northern California hospitals in 1993. Presented at The Pancreas Club, Inv. 30th Annual Meeting, San Francisco
Center for the Assessment and Management of Change in Academic Medicine (1998) Outcomes of complex, high-risk surgical procedures at high, moderate, and low volume hospitals: the example of Whipple’s procedure. AAMC Fact Sheet 2(3)
(1995) Health Care Financing Administration, OACT, Office of National Health Statistics. DRIVMcGraw-Hill HCC
Hannan EL, O’Donnell JF, Kilburn H et al (1989) Investigation of the relationship between volume and mortality for surgical procedures performed in New York State hospitals. JAMA 262(4):503–510
Luft HS, Bunker JP, Enthoven AC (1979) Should operations be regionalized? The empirical relation between surgical volume and mortality. N Engl J Med 301(25):1364–1369
Birkmeyer JD, Siewers AE, Finlayson EV et al (2002) Hospital volume and surgical mortality in the United States. N Engl J Med 346:1128
Gooiker GA, van Gijn W, Wouters MW et al (2011) Systematic review and meta-analysis of the volume-outcome relationship in pancreatic surgery. Br J Surg 98:485
Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29
Mayo SC, Gilson MM, Herman JM et al (2012) Management of patients with pancreatic adenocarcinoma national trends in patient selection, operative management, and use of adjuvant therapy. J Am Coll Surg 214:33–45
Jones S, Zhang X, Parsons DW et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:1801–1806
Balakrishnan A, Bleeker FE, Lamba S et al (2007) Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma. Cancer Res 67:3545–3550
Iacobuzio-Donahue CA (2011) Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. Gut
Hruban RH, van Mansfeld AD, Offerhaus GJ et al (1993) K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol 143:545
Almoguera C, Shibata D, Forrester K et al (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549
Moskaluk CA, Hruban RH, Kern SE (1997) p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res 57:2140
Jimenez RE, Warshaw AL, Z’graggen K et al (1999) Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy. Ann Surg 230:501
Shi C, Fukushima N, Abe T et al (2008) Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biol Ther 7:353
Kondo H, Sugano K, Fukayama N et al (1997) Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas. Cancer 79:900
Caldas C, Hahn SA, Hruban RH et al (1994) Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res 54:3568
Yachida S, White CM, Naito et al (2012) Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors. Clin Cancer Res 18(22):6339–6347
Iacobuzio-Donahue CA, Fu B, Yachida S et al (2009) DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 27:1806–1813
Biankin AV, Morey AL, Lee CS, Kench JG, Biankin SA, Hook HC et al (2002) DPC4/Smad4 expression and outcome in pancreatic ductal adenocarcinoma. J Clin Oncol 20:4531–4542
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Singh, T., Chaudhary, A. Improving Survival of Pancreatic Cancer. What Have We Learnt?. Indian J Surg 77, 436–445 (2015). https://doi.org/10.1007/s12262-015-1368-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12262-015-1368-7