A Retrospective Study on the Clinicopathological Characteristics and Prognostic Analysis of Gynecologic Neuroendocrine Carcinoma
ABSTRACT
Background
Gynecologic neuroendocrine carcinomas (NECs) are rare, highly aggressive malignancies with early metastatic potential and limited evidence to guide optimal management across different primary sites.
Aims
To characterize the clinicopathological features, treatment patterns, survival outcomes, and prognostic factors of gynecologic NECs (cervix, endometrium, and ovary) treated at a single tertiary center over a 10‐year period.
Materials and Methods
This observational, single‐center retrospective cohort study included patients diagnosed with gynecologic NEC at Women's Hospital, Zhejiang University School of Medicine, between January 2013 and August 2023. Clinicopathological data, treatment modalities, recurrence, and follow‐up outcomes were collected. Progression‐free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods. Prognostic factors were assessed using log‐rank tests and multivariable Cox proportional hazards models.
Results
A total of 52 patients were identified, of whom 78.8% had cervical NEC. Primary surgery was performed in 90.4% of patients; adjuvant chemotherapy and radiotherapy were administered in 65.4% and 51.9%, respectively. Among cervical NEC cases with HPV testing, 69.7% were HPV16/18‐positive. Immunohistochemical (IHC) showed high positivity for synaptophysin (95.3%) and chromogranin A (72.7%); Ki‐67 exceeded 50% in 89.1% of evaluated cases. Median PFS for cervical NEC was 29 months; stage I cervical NEC showed a 5‐year PFS of 51.6% and 5‐year OS of 68.4%. Poorer prognosis was associated with FIGO stage ≥ IB3, mixed neuroendocrine‐non‐neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma, tumor size > 4 cm, and lymph node metastasis. On multivariable analysis of cervical NEC, MiNEN with squamous cell carcinoma remained an independent predictor of reduced PFS (HR = 6.97, 95% CI: 1.60–30.31; p = 0.010).
Discussion
Despite multimodal treatment, gynecologic NECs showed poor outcomes. The identification of MiNEN with squamous cell carcinoma as an independent adverse factor for PFS suggests histologic composition may meaningfully affect prognosis and warrants validation in larger, multicenter cohorts.
Conclusion
Cervical NEC was the predominant subtype, most patients underwent surgery with adjuvant therapy, and survival was strongly stage‐dependent. MiNEN with squamous cell carcinoma independently predicted worse PFS, highlighting a potential high‐risk subgroup and reinforcing the need for multicenter prospective studies and more effective, potentially targeted treatment approaches for gynecologic NECs.