Pancreatic grade 3 neuroendocrine tumors behave similarly to neuroendocrine carcinomas following resection: a multi-center, international appraisal of the WHO 2010 and WHO 2017 staging schema for pancreatic neuroendocrine lesions

Abstract

Background: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors. Methods: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit.Results: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas. Conclusion:The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

“…A recent study of 28 patients operated with pancreatic NEN G−3 showed that NET G−3 have similar postoperative survival compared to NEC, which was significantly lower than for NET G−2 and G−1 [47]. Both localized and metastatic tumors were evaluated in this work, so it is hard to conclude [47]. As mentioned above, we can also speculate that NEC surgical trials probably evaluated some misdiagnosed NET G−3 [33,[43][44][45].…”

“…Nevertheless, surgery is still debated in localized NEC because of the high risk of metastatic relapse and the absence of prospective clinical trials; so neoadjuvant chemotherapy and chemoradiation can also be considered, especially when surgical resection is difficult or at risk [37,46]. A recent study of 28 patients operated with pancreatic NEN G−3 showed that NET G−3 have similar postoperative survival compared to NEC, which was significantly lower than for NET G−2 and G−1 [47]. Both localized and metastatic tumors were evaluated in this work, so it is hard to conclude [47].…”

“…In metastatic NEC surgery is not recommended, even if some data suggest a benefit on survival [45]. For NET G−3, data is scarce but contradictory with some work suggesting similar post-surgical outcome than NEC, and others suggesting overall survival is similar to NET G−2 [2,12,47]. There is also no specific data for liver-directed therapies in NET G−3.…”

Could pancreatic grade 3 neuroendocrine tumors really behave similarly to neuroendocrine carcinomas following resection?

“…Worth et al 1 reported that patients with resected G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) may have similar postoperative survival, a finding contradictory with current knowledge. [2][3][4] Of note, this study included only 15 patients with G3 NET and 13 with NEC.…”

Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions

“…One study on 28 patients operated for PanNEN G-3 suggested that patients with NET G-3 have similar postoperative survival compared to those with NEC, which was significantly lower than for NET G-2 and G-1 patients [ 81 ]. This is contradictory with current knowledge on NET G-3 prognosis and these results could be explained by the pooled evaluation of both localized and metastatic tumors [ 3 , 26 , 67 , 82 ].…”