Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: A comprehensive meta-analysis

Gynecol Oncol. 2022 Feb;164(2):446-454. doi: 10.1016/j.ygyno.2021.12.015. Epub 2021 Dec 20.

Abstract

Objective: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years.

Methods: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall.

Results: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81).

Conclusions: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

Keywords: Cervical cancer; Low-volume lymph node metastasis; Sentinel lymph node; Ultrastaging.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma / therapy
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Neoplasm Micrometastasis / pathology*
  • Neoplasm Staging
  • Sentinel Lymph Node / pathology*
  • Sentinel Lymph Node Biopsy
  • Survival Rate
  • Tumor Burden
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / therapy