Management paradigm for ovarian neuroendocrine carcinoma: a systematic review

Neuroendocrine neoplasms (NENs) of the female genital tract are rare, comprising only 1-2% of gynecologic tumors, with ovarian neuroendocrine carcinoma (O-NEC) accounting for less than 1% of all ovarian cancers. Despite its rarity, O-NEC is a highly aggressive tumor with poor prognosis and significant diagnostic complexity, warranting focused clinical attention and demand greater awareness to improve diagnostic and therapeutic strategies.

This systematic review analyzed management paradigm for O-NEC through a comprehensive search on the databases PubMed, Science Direct, Wiley, Springer Link, Google Scholar and Cochrane Central Register of Controlled Trials that was performed on August 1st, 2024.

A comprehensive search on August 1st, 2024, identified 21 eligible studies (6 retrospective cohorts, 12 case reports, 3 case series), encompassing 923 cases of O-NEC. The most common subtypes were small-cell (40%) and large-cell (39.8%) NEC. Most patients presented with advanced-stage (Stage III-IV: 52%). Immunohistochemical markers included synaptophysin (84%), chromogranin A (64.2%), CD56 (69%), and NSE (77.7%). Treatment varied from surgery alone (35%) or surgery plus chemotherapy (32%) being most common. No standardized regimen of chemotherapy was identified with etoposide/cisplatin and paclitaxel/carboplatin were most frequently used. Survival outcomes were poor, with median overall survival ranging from 11 to 23.5 months. The stage at diagnosis was a crucial prognostic factor.

The O-NEC is a rare, heterogeneous malignancy with diverse histopathology, variable immunohistochemical profiles, and generally poor prognosis. Early-stage disease may be managed with surgery alone, while advanced stages require multimodal treatment including surgery with adjuvant platinum-based chemotherapy. Due to limited cases and predominantly retrospective data, standardized diagnostic and treatment protocols are lacking. Prospective multicenter studies and centralized registries are needed to improve understanding and patient outcomes.