A Survival Analysis of Patients with Localized, Asymptomatic Pancreatic Neuroendocrine Tumors: No Surgical Survival Benefit when Examining Appropriately Selected Outcomes
Surgical resection for asymptomatic, localized, well-differentiated pancreatic neuroendocrine tumors (PNETs) is common yet controversial. Studies using overall survival as an endpoint have shown a benefit for resection; however, these results may be due to treatment selection bias. We assessed the impact of surgery on both overall (OS) and cancer-specific survival (CSS) for asymptomatic patients with stage I PNETs (AJCC 8th edition).
Using SEER data, we identified 709 patients from 2007 to 2015 with well- and moderately differentiated stage I PNETs. We performed Kaplan–Meier survival estimates and adjusted Cox regression for OS and CSS.
Among 709 patients, 628 (88.6%) underwent surgery. There were 37 overall deaths and 11 cancer-specific deaths. All cancer-specific deaths occurred within 3 years of diagnosis. Five-year OS and CSS rates were 89% and 98%, respectively, for the population. Five-year OS rates were 56% in the non-surgical cohort versus 92% in the surgical cohort (log rank, p < 0.001). However, the 5-year CSS rates were similar; 94% in the non-surgical group and 98% in the surgical group (log rank, p = 0.207). On multivariable analysis, surgery predicted improved OS but not CSS.
Although OS is superior in surgically treated stage I PNETs, CSS is not improved, implying treatment selection bias towards surgery being performed in healthier patients. These data suggest that overall survival is a problematic endpoint for the study of asymptomatic, stage I PNETs. Surgery should be individualized for this cohort of patients as the primary cause of death is non-cancer related.
KeywordsPancreas Neuroendocrine Tumor Surgery Survival
The authors thank Diana Castillo for her assistance with figure preparation.
Each author participated in the work to take public responsibility for appropriate portions of the content as per the guidelines of the International Committee of Medical Journal Editors (ICMJE). All authors made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND drafting the work or revising it critically for important intellectual content; AND final approval of the version to be published; AND agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 3.Zerbi A, Falconi M, Rindi G, Delle Fave G, Tomassetti P, Pasquali C et al. Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases. Am J Gastroenterol 2010;105(6):1421–9. doi: https://doi.org/10.1038/ajg.2009.747.CrossRefPubMedGoogle Scholar
- 4.Mansour JC, Chavin K, Morris-Stiff G, Warner SG, Cardona K, Fong ZV et al. Management of asymptomatic, well-differentiated PNETs: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association. HPB : the official journal of the International Hepato Pancreato Biliary Association 2018. https://doi.org/10.1016/j.hpb.2018.09.020.CrossRefGoogle Scholar
- 5.Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735–52. doi: https://doi.org/10.1097/MPA.0b013e3181ebb168.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95(2):157–76. doi: https://doi.org/10.1159/000335597.CrossRefPubMedGoogle Scholar
- 14.Finkelstein P, Sharma R, Picado O, Gadde R, Stuart H, Ripat C et al. Pancreatic Neuroendocrine Tumors (panNETs): Analysis of Overall Survival of Nonsurgical Management Versus Surgical Resection. J Gastrointest Surg 2017;21(5):855–66. doi: https://doi.org/10.1007/s11605-017-3365-6.CrossRefPubMedGoogle Scholar
- 15.Gratian L, Pura J, Dinan M, Roman S, Reed S, Sosa JA. Impact of extent of surgery on survival in patients with small nonfunctional pancreatic neuroendocrine tumors in the United States. Ann Surg Oncol 2014;21(11):3515–21. doi: https://doi.org/10.1245/s10434-014-3769-4.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Surveillance, Epidemiology, and End Results Program Overview. https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf. Accessed 28 Feb 2019.
- 19.National Comprehensive Cancer Network. Neuroendocrine and Adrenal Tumors (Version 3.2018). https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed January 20, 2018.
- 21.Swanson RS, Pezzi CM, Mallin K, Loomis AM, Winchester DP. The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the national cancer data base. Ann Surg Oncol 2014;21(13):4059–67. doi: https://doi.org/10.1245/s10434-014-4036-4.CrossRefPubMedGoogle Scholar