Clinicopathological characteristics and survival outcomes of patients with large cell neuroendocrine carcinoma of the uterine cervix: A systematic review and meta-analysis

Eur J Obstet Gynecol Reprod Biol. 2022 Mar:270:212-220. doi: 10.1016/j.ejogrb.2022.01.014. Epub 2022 Jan 17.

Abstract

Purpose: Large cell neuroendocrine carcinoma (LCNEC) of the cervix represents a rare tumour entity associated with poor prognosis. Knowledge about carcinogenesis and therapeutic options is scarce, while novel therapeutic targeted approaches are limited.

Methods: We performed a systematic review of four electronic databases from inception to June 2020. Eligible studies included all reports that addressed survival outcomes of women with LCNEC.

Results: A total of 31 case studies including 87 LCNEC patients were identified. Median patients' age was 41 years (range: 21-81). Most women (76.3%) had FIGO stage I-II disease. Overall, 72.0% had surgery, 70.1% received chemotherapy and 50.7% received radiotherapy. Of 13 patients with known HPV-status, 15% were HPV negative. Median overall survival (OS) was 24 months (range: 0.5-151), with 3- and 5-year OS of 42% and 29%, respectively. In multivariate analyses, only surgery and lymphadenectomy significantly associated with survival (Surgery OS: HR 0.14; 95% C.I:0.03-0.71, p = 0.018 / Surgery PFS: HR 0.23, 95% C.I. 0.06, 0.92, p = 0.037 / Lymphadenectomy OS: HR 0.26, 95% C.I. 0.07-0.98, p = 0.046 / Lymphadenectomy PFS: HR 0.30, 95% C.I. 0.09-0.98, p = 0.046). Age, chemotherapy or radiotherapy did not significantly impact survival, but lower stage was associated with improved survival.

Conclusion: Cervical LCNECs overall have a poor prognosis, despite their relatively early-stage initial presentation. Surgery and lymphadenectomy appear to significantly affect survival in contrast to chemotherapy and radiotherapy, which appear to have no significant effect on prognosis. Prospective multicentre cancer registries are warranted to improve treatment options for this rare disease.

Keywords: Cervical cancer; LCNEC; Large-cell neuroendocrine carcinoma; Neuroendocrine tumour; Prognosis; Survival.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Large Cell* / pathology
  • Carcinoma, Large Cell* / therapy
  • Carcinoma, Neuroendocrine* / drug therapy
  • Carcinoma, Neuroendocrine* / pathology
  • Cervix Uteri / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Uterine Cervical Neoplasms* / pathology
  • Young Adult