Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Ann Surg Oncol. 2022 Oct;29(11):6936-6946. doi: 10.1245/s10434-022-12100-3. Epub 2022 Jul 8.
Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are aggressive tumors with poor survival outcomes for which medical management is generally recommended. This study sought to evaluate outcomes of surgically treated G3 GEP-NEN patients.
A single-institutional prospective NEN database was reviewed. Patients with G3 GEP-NENs based on World Health Organization (WHO) 2019 definitions included well-differentiated neuroendocrine tumors (G3NET) and poorly differentiated neuroendocrine carcinomas (G3NEC). Clinicopathologic factors were compared between groups. Overall survival from G3 diagnosis was assessed by the Kaplan-Meier method.
Surgical resection was performed for 463 patients (211 G1, 208 G2, 44 G3). Most had metastatic disease at presentation (54% G1, 69% G2, 91% G3; p < 0.001). The G3 cohort included 39 G3NETs and 5 G3NECs, 22 of pancreatic and 22 of midgut origin. Median overall survival (mOS; in months) was 268.1 for G1NETs, 129.9 for G2NETs, 50.5 for G3NETs, and 28.5 for G3NECs (p < 0.001). Over the same period, 31 G3 patients (12 G3NETs, 19 G3NECs) were treated non-surgically, with mOS of 19.0 for G3NETs and 12.4 for G3NECs.
Surgical resection of G3 GEP-NENs remains controversial due to poor prognosis, and surgical series are rare. This large, single-institutional study found significantly lower mOS in patients with resected G3NENs than those with G1/G2 tumors, reflecting more aggressive tumor biology and a higher proportion with metastatic disease. The mOS for resected G3NETs and G3NECs exceeded historical non-surgical G3NEN series (mOS 11-19 months), suggesting surgery should be considered in carefully selected patients with G3NENs, especially those with well-differentiated tumors.
3 级（G3）胃肠胰神经内分泌肿瘤（GEP-NEN）是一种侵袭性肿瘤，生存预后较差，一般建议采用医学治疗。本研究旨在评估手术治疗 G3 GEP-NEN 患者的结果。
回顾单机构前瞻性 NEN 数据库。根据世界卫生组织（WHO）2019 年定义，G3 GEP-NEN 患者包括高分化神经内分泌肿瘤（G3NET）和低分化神经内分泌癌（G3NEC）。比较两组患者的临床病理特征。采用 Kaplan-Meier 法评估 G3 诊断后的总生存情况。
463 例患者接受了手术切除（G1 211 例、G2 208 例、G3 44 例）。大多数患者在就诊时已发生转移（G1 为 54%，G2 为 69%，G3 为 91%；p<0.001）。G3 组包括 39 例 G3NET 和 5 例 G3NEC，其中 22 例源自胰腺，22 例源自中肠。G1NET、G2NET、G3NET 和 G3NEC 的中位总生存（mOS；月）分别为 268.1、129.9、50.5 和 28.5（p<0.001）。同期，31 例 G3 患者（12 例 G3NET、19 例 G3NEC）接受非手术治疗，G3NET 的 mOS 为 19.0，G3NEC 的 mOS 为 12.4。
由于预后较差，G3 GEP-NEN 的手术切除仍存在争议，且手术系列报道罕见。这项大型单机构研究发现，与 G1/G2 肿瘤相比，接受 G3NEN 切除术的患者 mOS 明显较低，这反映出肿瘤生物学更具侵袭性，且转移疾病的比例更高。接受 G3NET 和 G3NEC 切除术的患者 mOS 超过历史上非手术 G3NEN 系列（mOS 11-19 个月），提示应考虑在经过精心选择的 G3NEN 患者中进行手术，尤其是那些分化较好的肿瘤患者。
