Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis
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There is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival.
Patients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis.
A total of 442 stage IV P-NET patients were identified, of whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of death = 0.41, 95 % confidence interval [CI] 0.25–0.66, p < 0.001) and cancer-specific survival (HR of death = 0.41, 95 % CI 0.25–0.67, p < 0.001) in unadjusted multivariate Cox regression analysis; the benefit persisted after propensity score adjustment.
This population-based analysis of stage IV P-NET patients provides compelling evidence that palliative resection of the primary tumor is associated with significant survival benefit. Thus, the recent recommendations judging resection of the primary as inadvisable and the accompanying trend towards fewer palliative resections of the primary tumor have to be contested.
KeywordsPancreatic neuroendocrine tumors Metastases Primary tumor resection Palliative Survival
The authors thank the National Cancer Institute for providing the SEER registry data.
No funding was received for this study.
Conflicts of interest
The authors declare that no conflicts of interest exist in relation to this study.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Since the data source for this retrospective study was the SEER database of the National Cancer Institute of the United States of America, no formal consent is required for this type of study.
- 3.Vagefi PA, Razo O, Deshpande V, McGrath DJ, Lauwers GY, Thayer SP, Warshaw AL, Fernandez-Del CC (2007) Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg 142(4):347–354PubMedCentralCrossRefPubMedGoogle Scholar
- 4.Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26(18):3063–3072CrossRefPubMedGoogle Scholar
- 15.Falconi M, Bartsch DK, Eriksson B, Kloppel G, Lopes JM, O’Connor JM, Salazar R, Taal BG, Vullierme MP, O’Toole D, Barcelona Consensus Conference, Barcelona Consensus Conference p (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology 95(2):120–134CrossRefPubMedGoogle Scholar
- 16.Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, Scoazec JY, Salazar R, Sauvanet A, Kianmanesh R, Barcelona Consensus Conference p (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology 95(2):98–119PubMedCentralCrossRefPubMedGoogle Scholar
- 19.Wingo PA, Jamison PM, Hiatt RA, Weir HK, Gargiullo PM, Hutton M, Lee NC, Hall HI (2003) Building the infrastructure for nationwide cancer surveillance and control—a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States). Cancer Causes Control 14(2):175–193CrossRefPubMedGoogle Scholar
- 20.Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin DM, Whelan S (2000) International Classification of Disease for Oncology, 3rd edn. World Health Organization, Geneva, SwitzerlandGoogle Scholar
- 25.Rosche M, Regierer AC, Schwarzlose-Schwarck S, Weigel A, Bangemann N, Schefe JH, Scholz CW, Possinger K, Eucker J (2011) Primary tumor excision in stage IV breast cancer at diagnosis without influence on survival: a retrospective analysis and review of the literature. Onkologie 34(11):607–612CrossRefPubMedGoogle Scholar
- 26.Frilling A, Modlin IM, Kidd M, Russell C, Breitenstein S, Salem R, Kwekkeboom D, Lau WY, Klersy C, Vilgrain V, Davidson B, Siegler M, Caplin M, Solcia E, Schilsky R, Working Group on Neuroendocrine Liver M (2014) Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol 15(1):e8–e21CrossRefPubMedGoogle Scholar
- 29.Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K, Rad001 in Advanced Neuroendocrine Tumors T.T.S.G. (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364(6):514–523PubMedCentralCrossRefPubMedGoogle Scholar
- 30.Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Horsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364(6):501–513CrossRefPubMedGoogle Scholar
- 31.Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Macke HR, Rochlitz C, Muller-Brand J, Walter MA (2011) Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 29(17):2416–2423CrossRefPubMedGoogle Scholar
- 32.Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, Ng QK, Macke HR, Muller-Brand J, Rochlitz C, Briel M, Walter MA (2012) Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 30(10):1100–1106CrossRefPubMedGoogle Scholar
- 35.Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N (2011) DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331(6021):1199–1203PubMedCentralCrossRefPubMedGoogle Scholar