Clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix.

Objective: To describe the clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix at the population level in the United States.

Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried. The study population included 54,987 patients with cervical cancer from 2004 to 2021. Descriptive analysis was performed based on histology.

Results: Histology types included squamous cell carcinoma (n = 38,145, 69.4%), adenocarcinoma (n = 14,333, 26.1%), adenosquamous carcinoma (n = 1,970, 3.6%), and small cell neuroendocrine carcinoma (n = 539, 1.0%). Over the 18-year study period, the incidence rate of small cell neuroendocrine carcinoma increased by 3.2% per year (95% CI 1.2 to 5.7, p = .003). Based on this trajectory, the incidence of small cell neuroendocrine carcinoma is estimated to reach 2.0% by 2035. Small cell neuroendocrine carcinoma was associated with larger cervical tumors (60 mm versus 27-40 mm), a higher lymph node metastasis ratio (25.0% versus 14.3%-15.4%), higher distant metastasis rate even in small tumor (10 mm, 10.3% versus 0.5-2.6%; and 20 mm, 14.8% versus 3.9-5.3%), and stage IV disease (40.1% versus 11.9%-15.2%) than other histologies (p < .001). Among distant metastasis cases, small cell neuroendocrine carcinoma was more likely to spread to the liver (36.1% versus 14.3%-15.4%) or bone (28.8% versus 17.3%-19.1%) and to involve multiple distant organ metastases (≥2 organs: 37.3% vs 27.8%-30.2%; and ≥3 organs: 18.1% vs 9.2%-10.1%) compared with other histologies (p < .001). Across stages I to IV, small cell neuroendocrine carcinoma had lower 5-year overall survival rates than other histologies: stage I, 58.0% versus 82.5% to 91.3%; stage II, 38.4% versus 60.7% to 64.6%; stage III, 31.3% versus 49.5% to 51.4%; and stage IV, 8.1% versus 18.2% (p < .05). Early-death rates within two months from diagnosis of small cell neuroendocrine carcinoma were substantially higher than other histologies (9.0% vs 2.2%, p < .001).

Conclusions: This population-based assessment suggests that, although rare, the incidence of small cell neuroendocrine carcinoma of the uterine cervix is gradually increasing in the United States. Multiple distant organ metastases, especially to the liver and bone, and poor survival outcomes characterize small cell neuroendocrine carcinoma of the uterine cervix.