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.