Ioannis A Ziogas1,2, Panagiotis T Tasoudis2, Luis C Borbon3, Scott K Sherman3, Patrick J Breheny4, Chandrikha Chandrasekharan5, Joseph S Dillon5, Andrew M Bellizzi6, James R Howe7. 1. Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. 2. Surgery Working Group, Society of Junior Doctors, Athens, Greece. 3. Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA. 4. Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA, USA. 5. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA. 6. Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA. 7. Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA. james-howe@uiowa.edu.
Abstract
BACKGROUND: Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare, aggressive tumors with poor prognosis. The World Health Organization 2017 and 2019 classifications further subdivided G3 NENs into G3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Current guidelines favor medical management in most of these patients, and the role of surgical management is not well defined. We performed a systematic literature review and meta-analysis of surgical management versus nonsurgical management for G3 GEP NENs. MATERIALS AND METHODS: A PRISMA-compliant systematic review of the MEDLINE, Embase, Scopus, and Cochrane Library databases (end-of-search date: 16 July 2021) was conducted. Individual patient survival data were reconstructed, and random-effects meta-analyses were performed. RESULTS: Fourteen studies comprising 1810 surgical and 910 nonsurgical patients were systematically reviewed. Publication bias adjusted meta-analysis of 12 studies (1788 surgical and 857 nonsurgical patients) showed increased overall survival (OS) after surgical compared with nonsurgical management for G3 GEP NENs [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.31-0.53]. Subgroup meta-analyses showed increased OS after surgical management for both pancreatic and gastrointestinal primary sites separately. In another subgroup meta-analysis of G3 GEP NETs (not NECs), surgical management was associated with increased OS compared with nonsurgical management (HR 0.26, 95% CI 0.11-0.61). CONCLUSIONS: Surgical management of G3 GEP NENs may provide a potential survival benefit in well-selected cases. Further research is needed to define which patients will benefit most from surgical versus nonsurgical management. The current literature is limited by inconsistent reporting of survival outcomes in surgical versus nonsurgical groups, tumor grade, differentiation, primary tumor site, and selection criteria for surgical and nonsurgical management.
BACKGROUND: Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare, aggressive tumors with poor prognosis. The World Health Organization 2017 and 2019 classifications further subdivided G3 NENs into G3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Current guidelines favor medical management in most of these patients, and the role of surgical management is not well defined. We performed a systematic literature review and meta-analysis of surgical management versus nonsurgical management for G3 GEP NENs. MATERIALS AND METHODS: A PRISMA-compliant systematic review of the MEDLINE, Embase, Scopus, and Cochrane Library databases (end-of-search date: 16 July 2021) was conducted. Individual patient survival data were reconstructed, and random-effects meta-analyses were performed. RESULTS: Fourteen studies comprising 1810 surgical and 910 nonsurgical patients were systematically reviewed. Publication bias adjusted meta-analysis of 12 studies (1788 surgical and 857 nonsurgical patients) showed increased overall survival (OS) after surgical compared with nonsurgical management for G3 GEP NENs [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.31-0.53]. Subgroup meta-analyses showed increased OS after surgical management for both pancreatic and gastrointestinal primary sites separately. In another subgroup meta-analysis of G3 GEP NETs (not NECs), surgical management was associated with increased OS compared with nonsurgical management (HR 0.26, 95% CI 0.11-0.61). CONCLUSIONS: Surgical management of G3 GEP NENs may provide a potential survival benefit in well-selected cases. Further research is needed to define which patients will benefit most from surgical versus nonsurgical management. The current literature is limited by inconsistent reporting of survival outcomes in surgical versus nonsurgical groups, tumor grade, differentiation, primary tumor site, and selection criteria for surgical and nonsurgical management.
Authors: R Garcia-Carbonero; H Sorbye; E Baudin; E Raymond; B Wiedenmann; B Niederle; E Sedlackova; C Toumpanakis; M Anlauf; J B Cwikla; M Caplin; D O'Toole; A Perren Journal: Neuroendocrinology Date: 2016-01-05 Impact factor: 4.914
Authors: James R Howe; Nipun B Merchant; Claudius Conrad; Xavier M Keutgen; Julie Hallet; Jeffrey A Drebin; Rebecca M Minter; Terry C Lairmore; Jennifer F Tseng; Herbert J Zeh; Steven K Libutti; Gagandeep Singh; Jeffrey E Lee; Thomas A Hope; Michelle K Kim; Yusuf Menda; Thorvardur R Halfdanarson; Jennifer A Chan; Rodney F Pommier Journal: Pancreas Date: 2020-01 Impact factor: 3.327
Authors: Olca Basturk; Laura Tang; Ralph H Hruban; Volkan Adsay; Zhaohai Yang; Alyssa M Krasinskas; Efsevia Vakiani; Stefano La Rosa; Kee-Taek Jang; Wendy L Frankel; Xiuli Liu; Lizhi Zhang; Thomas J Giordano; Andrew M Bellizzi; Jey-Hsin Chen; Chanjuan Shi; Peter Allen; Diane L Reidy; Christopher L Wolfgang; Burcu Saka; Neda Rezaee; Vikram Deshpande; David S Klimstra Journal: Am J Surg Pathol Date: 2014-04 Impact factor: 6.394
Authors: H Sorbye; S Welin; S W Langer; L W Vestermark; N Holt; P Osterlund; S Dueland; E Hofsli; M G Guren; K Ohrling; E Birkemeyer; E Thiis-Evensen; M Biagini; H Gronbaek; L M Soveri; I H Olsen; B Federspiel; J Assmus; E T Janson; U Knigge Journal: Ann Oncol Date: 2012-09-11 Impact factor: 32.976
Authors: Arvind Dasari; Chan Shen; Daniel Halperin; Bo Zhao; Shouhao Zhou; Ying Xu; Tina Shih; James C Yao Journal: JAMA Oncol Date: 2017-10-01 Impact factor: 31.777
Authors: Iris D Nagtegaal; Robert D Odze; David Klimstra; Valerie Paradis; Massimo Rugge; Peter Schirmacher; Kay M Washington; Fatima Carneiro; Ian A Cree Journal: Histopathology Date: 2019-11-13 Impact factor: 5.087