ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
J Neuroendocrinol. 2021 May;33(5):e12967. doi: 10.1111/jne.12967. Epub 2021 Mar 26.
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.
高分级胃肠胰神经内分泌肿瘤（GEP NEN）和混合性神经内分泌-非神经内分泌肿瘤（MiNEN）的手术获益尚不确定。本研究旨在探讨 Ki-67＞20%的高分级 GEP NEN 或 MiNEN Ⅰ-Ⅲ期或Ⅳ期患者肿瘤手术后的结局。我们分析了 2007 年至 2015 年在 8 家北欧大学医院治疗的患者的数据。采用 Kaplan-Meier 估计法分析总生存（OS）和无进展生存（PFS）/无病生存（DFS）。使用 Cox 回归评估预后因素。我们纳入了 201 例接受手术切除的患者，其中 143 例为Ⅰ-Ⅲ期，58 例为Ⅳ期，68%为神经内分泌癌，23%为 MiNEN，5%为 G3 神经内分泌肿瘤，4%为不确定 NEN G3。原发肿瘤位于结肠/直肠（52%）、食管/贲门（19%）、胰腺（10%）、胃（7%）、空肠/回肠（5%）、十二指肠（4%）、胆囊（2%）和肛管（1%）。对于Ⅰ-Ⅲ期患者，中位 DFS 为 12 个月（95%CI=5.5-18.5），中位 OS 为 32 个月（95%CI=24.0-40.0）。对于Ⅰ-Ⅲ期且 R0 切除的患者，中位 DFS 为 21 个月（95%CI=4.9-37.1），中位 OS 为 39 个月（95%CI=25.0-53.0）。对于Ⅳ期患者，中位 PFS/DFS 为 4 个月（95%CI=1.9-6.1），中位 OS 为 11 个月（95%CI=4.8-17.2）。对于Ⅳ期且 R0 切除的患者，中位 DFS 为 6 个月（95%CI=0-16.4），中位 OS 为 32 个月（95%CI=25.5-38.5）。ECOG 体能状态＞1 分和结直肠原发肿瘤与预后不良相关。高分级 GEP NEN 和 MiNEN 患者的生存无差异。对于局部进展期高分级 GEP NEN 或 MiNEN 患者，行原发肿瘤切除术可获得良好的长期结果，如果可达到 R0 切除，应考虑手术治疗。高度选择的Ⅳ期疾病患者也可能从手术中获益。
