Department of Medical Oncology, Ioannina University Hospital, Greece.
Cancer Treat Rev. 2011 Aug;37(5):358-65. doi: 10.1016/j.ctrv.2011.03.002. Epub 2011 Apr 9.
Neuroendocrine carcinomas of unknown primary (NCUP) represent a specific subset with relatively favorable prognosis. Data on biology, management and outcome of NCUP patients have not been systematically reviewed neither compared to those of neuroendocrine tumors of known primary.
We systematically reviewed all publications studying neuroendocrine CUP patients and presented a single center retrospective patient series. In addition, we analyzed and specified the similarities and/or differences between NCUP and other neuroendocrine malignancies.
Five hundred patients with NCUP constituted a heterogeneous cohort in terms of histology, grade, anatomic site and tumor biology in published series and were managed mostly with platinum-based regimens. Among 294 patients with available outcome data, a median survival of 15.5 months (range 11.6-40) was observed. Comparative analysis with neuroendocrine solid tumors (NET) revealed that poorly-differentiated NCUP share an aggressive natural history and a dismal prognosis similar to high grade pulmonary and extrapulmonary neuroendocrine carcinomas (Large Cell Neuroendocrine bronchial Carcinomas, LCNEC and poorly differentiated gastroenteropancreatic tumors, GEP-NET). Well differentiated NCUP reveal a more indolent course with a survival range resembling that of typical and atypical pulmonary carcinoids, well differentiated gastrointestinal NETs and limited small cell lung carcinomas.
No evidence for distinct biology or outcome of NCUP patients emerged when histological grade was matched for known primary NETs. The high heterogeneity of the NCUP subgroup limits the potential for identification of reliable prognosticators and hinders development of novel targeted therapies.
原发灶不明的神经内分泌癌（NCUP）是一类具有相对较好预后的特殊亚型。关于 NCUP 患者的生物学特性、治疗和预后的数据尚未进行系统评价，也未与已知原发性神经内分泌肿瘤的数据进行比较。
我们系统地回顾了所有研究神经内分泌癌的文献，并展示了一个单中心回顾性患者系列。此外，我们分析并指出了 NCUP 与其他神经内分泌恶性肿瘤之间的相似之处和/或差异。
500 例 NCUP 患者在发表的系列中构成了一个组织学、分级、解剖部位和肿瘤生物学均具有异质性的队列，主要采用铂类为基础的方案进行治疗。在 294 例可获得生存数据的患者中，中位生存时间为 15.5 个月（范围 11.6-40）。与神经内分泌实体瘤（NET）的比较分析显示，低分化的 NCUP 具有侵袭性的自然病史和与高分级肺和肺外神经内分泌癌（大细胞神经内分泌支气管癌、LCNEC 和分化差的胃肠胰神经内分泌肿瘤、GEP-NET）相似的不良预后。高分化 NCUP 则表现出更惰性的病程，其生存范围与典型和非典型肺类癌、分化良好的胃肠神经内分泌肿瘤和局限性小细胞肺癌相似。
当组织学分级与已知原发性 NET 相匹配时，没有证据表明 NCUP 患者具有独特的生物学特性或预后。NCUP 亚组的高度异质性限制了识别可靠预后标志物的潜力，并阻碍了新型靶向治疗的发展。
