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Research Article| Volume 165, ISSUE 3, P644-651, March 2019

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Resection of primary tumor may prolong survival in metastatic gastroenteropancreatic neuroendocrine tumors

Published:October 23, 2018DOI:https://doi.org/10.1016/j.surg.2018.09.006

      Background

      Patients with gastroenteropancreatic neuroendocrine tumors often present with stage IV disease. Primary tumor resection in these patients remains controversial. Herein, we studied the impact of primary tumor removal, identified variables associated with prolonged survival for each neuroendocrine tumor subtype, and determined factors that influence surgeons to perform primary tumor resection.

      Methods

      Patients with metastatic gastroenteropancreatic neuroendocrine tumors diagnosed from 2004 to 2014 were identified from the National Cancer Database. Nested Cox proportional hazards and logistic regression models were used to assess variables associated with survival and primary resection.

      Results

      A total of 14,510 patients met inclusion criteria. On multivariable analysis, resection of the primary tumor and grade 1 or 2 tumors was associated with prolonged survival in all subtypes (P < .001). Organ-specific variables associated with prolonged survival in patients undergoing primary tumor resection included the following: low grade for all organs; young age for pancreatic, small intestinal, colonic, and rectal neuroendocrine tumor; tumor size for colonic and rectal neuroendocrine tumor; and tumor location for colonic neuroendocrine tumor. Low tumor grade was found to be significantly associated with removal of the primary tumor across all organs.

      Conclusion

      This study is the first suggesting that primary tumor resection is associated with prolonged survival for all gastro-entero-pancreatic NETs. Additional variables related to survival for each NET subtype were identified and might help select patients who benefit from primary tumor removal.

      Keywords

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      References

        • Klöppel G.
        • Dege K.
        • Remmele W.
        • Kapran Y.
        • Tuzlali S.
        • Modlin I.M.
        Siegfried Oberndorfer: A tribute to his work and life between Munich, Kiel, Geneva, and Istanbul.
        Virchows Arch Int J Pathol. 2007; 451: S3-S7
        • Bosman F.T.
        • World Health Organization, International Agency for Research on Cancer
        WHO classification of tumours of the digestive system.
        4th ed. International Agency for Research on Cancer, Lyon, France2010
        • Pavel M.
        • O'Toole D.
        • Costa F.
        • Capdevila J.
        • Gross D.
        • Kianmanesh R.
        • et al.
        ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site.
        Neuroendocrinology. 2016; 103: 172-185
        • Yao J.C.
        • Hassan M.
        • Phan A.
        • Dagohoy C.
        • Leary C.
        • Mares J.E.
        • et al.
        One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.
        J Clin Oncol. 2008; 26: 3063-3072
        • Hallet J.
        • Law C.H.L.
        • Cukier M.
        • Saskin R.
        • Liu N.
        • Singh S.
        Exploring the rising incidence of neuroendocrine tumors: A population-based analysis of epidemiology, metastatic presentation, and outcomes.
        Cancer. 2015; 121: 589-597
        • Chi W.
        • Warner R.R.P.
        • Chan D.L.
        • Singh S.
        • Segelov E.
        • Strosberg J.
        • et al.
        Long-term outcomes of gastroenteropancreatic neuroendocrine tumors.
        Pancreas. 2018; 47: 321-325
        • Sarmiento J.M.
        • Heywood G.
        • Rubin J.
        • Ilstrup D.M.
        • Nagorney D.M.
        • Que F.G.
        Surgical treatment of neuroendocrine metastases to the liver: A plea for resection to increase survival.
        J Am Coll Surg. 2003; 197: 29-37
        • Bagante F.
        • Spolverato G.
        • Merath K.
        • Postlewait L.M.
        • Poultsides G.A.
        • Mullen M.G.
        • et al.
        Neuroendocrine liver metastasis: The chance to be cured after liver surgery.
        J Surg Oncol. 2017; 115: 687-695
        • Farley H.A.
        • Pommier R.F.
        Treatment of neuroendocrine liver metastases.
        Surg Oncol Clin N Am. 2016; 25: 217-225
        • Graff-Baker A.N.
        • Sauer D.A.
        • Pommier S.J.
        • Pommier R.F.
        Expanded criteria for carcinoid liver debulking: Maintaining survival and increasing the number of eligible patients.
        Surgery. 2014; 156 (discussion 1376–7): 1369-1376
        • Lewis A.
        • Raoof M.
        • Ituarte P.H.G.
        • Williams J.
        • Melstrom L.
        • Li D.
        • et al.
        Resection of the primary gastrointestinal neuroendocrine tumor improves survival with or without liver treatment.
        Ann Surg. 2018; ([Epub ahead of print])https://doi.org/10.1097/SLA.0000000000002809
      1. About the National Cancer Database. American College of Surgeons Web site. https://www.facs.org/quality-programs/cancer/ncdb/about. Accessed 17 November 2017.

      2. R Core Team Web site. Vienna, Austria: R Foundation for Statistical Computing; 2016. https://www.R-project.org/. Accessed 1 October 2017.

        • Keutgen X.M.
        • Nilubol N.
        • Glanville J.
        • Sadowski S.M.
        • Liewehr D.J.
        • Venzon D.J.
        • et al.
        Resection of primary tumor site is associated with prolonged survival in metastatic nonfunctioning pancreatic neuroendocrine tumors.
        Surgery. 2016; 159: 311-318
        • Givi B.
        • Pommier S.J.
        • Thompson A.K.
        • Diggs B.S.
        • Pommier R.F.
        Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival.
        Surgery. 2006; 140: 891-898
        • Hill J.S.
        • McPhee J.T.
        • McDade T.P.
        • Zhou Z.
        • Sullivan M.E.
        • Whalen G.F.
        • et al.
        Pancreatic neuroendocrine tumors: The impact of surgical resection on survival.
        Cancer. 2009; 115: 741-751
        • Tao L.
        • Xiu D.
        • Sadula A.
        • Ye C.
        • Chen Q.
        • Wang H.
        • et al.
        Surgical resection of primary tumor improves survival of pancreatic neuroendocrine tumor with liver metastases.
        Oncotarget. 2017; 8: 79785-79792
        • Bertani E.
        • Fazio N.
        • Radice D.
        • Zardini C.
        • Spinoglio G.
        • Chiappa A.
        • et al.
        Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail.
        A propensity score survival evaluation. Eur J Surg Oncol. 2017; 43: 372-379
        • Lidsky M.E.
        • Sun Z.
        • Nussbaum D.P.
        • Adam M.A.
        • Speicher P.J.
        • Blazer D.G.
        Going the extra mile: Improved survival for pancreatic cancer patients traveling to high-volume centers.
        Ann Surg. 2017; 266: 333-338
        • Shafqat H.
        • Ali S.
        • Salhab M.
        • Olszewski A.J.
        Survival of patients with neuroendocrine carcinoma of the colon and rectum: A population-based analysis.
        Dis Colon Rectum. 2015; 58: 294-303
        • Fitzgerald T.L.
        • Mosquera C.
        • Lea C.S.
        • McMullen M.
        Primary site predicts grade for gastroenteropancreatic neuroendocrine tumors.
        Am Surg. 2017; 83: 799-803
        • Corey B.
        • Chen H.
        Neuroendocrine tumors of the stomach.
        Surg Clin North Am. 2017; 97: 333-343
        • Li T-T
        • Qiu F.
        • Qian Z.R.
        • Wan J.
        • Qi X-K
        • Wu B-Y
        Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors.
        World J Gastroenterol WJG. 2014; 20: 118-125
        • Coan K.E.
        • Gray R.J.
        • Schlinkert R.T.
        • Pockaj B.A.
        • Wasif N.
        Metastatic carcinoid tumors—Are we making the cut?.
        Am J Surg. 2013; 205: 642-646
        • Boudreaux J.P.
        • Klimstra D.S.
        • Hassan M.M.
        • Woltering E.A.
        • Jensen R.T.
        • Goldsmith S.J.
        • et al.
        The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: Well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum.
        Pancreas. 2010; 39: 753-766
        • Kulke M.H.
        • Anthony L.B.
        • Bushnell D.L.
        • de Herder W.W.
        • Goldsmith S.J.
        • Klimstra D.S.
        • et al.
        NANETS treatment guidelines: Well-differentiated neuroendocrine tumors of the stomach and pancreas.
        Pancreas. 2010; 39: 735-752