Surgery of the primary tumour in 201 patients with high‐grade gastroenteropancreatic neuroendocrine and mixed neuroendocrine‐non‐neuroendocrine neoplasms

The benefit of surgery in high‐grade gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) and mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNEN) is uncertain. The present study aimed to investigate outcomes after tumour surgery in patients with high‐grade (Ki‐67 > 20%) GEP NEN or MiNEN stage I‐III or stage IV. We analysed data from patients treated in the period 2007‐2015 at eight Nordic university hospitals. Overall survival (OS) and progression‐free survival (PFS)/disease‐free survival (DFS) were analysed by Kaplan‐Meier estimates. Prognostic factors were evaluated using Cox regression. We included 201 surgically resected patients, 143 stage I‐III and 58 stage IV, with 68% having neuroendocrine carcinoma, 23% MiNEN, 5% neuroendocrine tumour G3 and 4% uncertain NEN G3. Primary tumours were located in colon/rectum (52%), oesophagus/cardia (19%), pancreas (10%), stomach (7%), jejunum/ileum (5%), duodenum (4%), gallbladder (2%) and anal canal (1%). For patients with stage I‐III, median DFS was 12 months (95% confidence interval [CI] = 5.5‐18.5) and median OS was 32 months (95% CI = 24.0‐40.0). For patients with stage I‐III and an R0 resection, median DFS was 21 months (95% CI = 4.9‐37.1) and median OS was 39 months (95% CI = 25.0‐53.0). For patients with stage IV, median PFS/DFS was 4 months (95% CI = 1.9‐6.1) and median OS was 11 months (95% CI = 4.8‐17.2). For patients with stage IV and an R0 resection, median DFS was 6 months (95% CI = 0‐16.4) and median OS was 32 months (95% CI = 25.5‐38.5). Performance status > 1 and colorectal primary were associated with poor prognosis. There was no difference in survival between patients with high‐grade GEP NEN and MiNEN. Surgery of the primary tumour in patients with loco‐regional high‐grade GEP NEN or MiNEN led to good long‐term results and should be considered if an R0 resection is considered achievable. Highly selected patients with stage IV disease may also benefit from surgery. We present the largest study reported to date in patients undergoing surgical resection for high‐grade gastroenteropancreatic neuroendocrine neoplasms or mixed neuroendocrine‐non‐neuroendocrine neoplasms. We conclude that surgery is beneficial if an R0 resection margin can be obtained. These results may impact future clinical guidelines.