Luis C. Borbon, MD
General Surgery Resident
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are aggressive tumors with poor survival outcomes. Therefore, medical management has generally been recommended over surgery. The aim of this study was to evaluate outcomes of surgically treated G3 GEP-NEN patients.
Methods:
A single-institutional prospective NEN database was reviewed. Patients with G3 tumors (WHO 2019; Ki-67 >20%, mitotic index >20) included well-differentiated neuroendocrine tumors (G3NET) and poorly-differentiated neuroendocrine carcinoma (G3NEC). Pulmonary, hindgut, and mixed-NENs (MiNENs) were excluded. Clinicopathologic factors were compared between patient groups. The primary outcome was overall survival from G3 diagnosis, which was assessed by the Kaplan-Meier method.
Results:
Surgery (primary resection and/or cytoreduction) was performed on 464 patients (211 G1, 208 G2, 45 G3). Most had metastatic disease at presentation (55% G1, 71% G2, 91% G3; p-value = 7.5e-07). The G3 cohort included 39 G3NETs and 6 G3NECs; 23 originated in the pancreas and 22 in the midgut. The median overall survival (mOS; in months) was 50.5 for G3NETs and 31.0 for G3NECs, while mOS for G1 was 268.1 and G2 was 129.9 (Figure). In G3 NENs, 13 were known to be G3 prior to their initial operation, 22 were diagnosed as G3 after the initial operation, and 10 progressed to G3 after initial surgery for a G1/G2 tumor; survival was not significantly different between these groups. Over the same period, there were 31 G3 patients (12 G3NETs, 19 G3NECs) treated non-surgically, with mOS of 19.0 for G3NETs and 12.4 for G3NECs.
Conclusions:
Surgical resection of G3 GEP-NENs remains controversial due to poor prognosis, and surgical series are rare. This large single institutional study shows significantly lower mOS in patients with resected G3NENs than those with G1/G2 tumors, likely related to more aggressive tumor biology and a higher proportion with metastatic disease. The mOS for resected G3NETs and G3NECs exceeded historical non-surgical G3NEN series (where mOS ranges from 11-18 months), suggesting surgery should be considered in carefully selected patients with G3NENs, especially those with well-differentiated tumors.