Serum Neuroendocrine Markers Predict Therapy Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis

Urol Int. 2019;102(4):373-384. doi: 10.1159/000495512. Epub 2018 Dec 5.

Abstract

Purpose: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias.

Results: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers' levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469-9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774-8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315-5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017-1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly.

Conclusions: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.

Keywords: Castration-resistant prostate cancer; Chromogranin A; Meta-analysis; Neuroendocrine; Neurone-specific enolase.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Case-Control Studies
  • Chromogranin A / blood*
  • Disease-Free Survival
  • Humans
  • Male
  • Middle Aged
  • Phosphopyruvate Hydratase / blood*
  • Prognosis
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CHGA protein, human
  • Chromogranin A
  • Prostate-Specific Antigen
  • Phosphopyruvate Hydratase