Prognostic factors of metastatic neuroendocrine carcinoma under first-line treatment with platinum etoposide with a focus on NEC score and Rb expression: Results from the multicentre RBNEC study of the Groupe d'Etude des Tumeurs Endocrines (GTE) and the ENDOCAN-RENATEN network

Eur J Cancer. 2021 Jul:152:100-115. doi: 10.1016/j.ejca.2021.04.030. Epub 2021 Jun 3.


Introduction and aim: Neuroendocrine carcinomas (NECs) are aggressive malignant diseases. Platinum-etoposide (PE) combination is the standard first-line treatment, whatever the primary location. The NEC score and also retinoblastoma protein (Rb) status have been suggested to be predictive/prognostic factors in NEC. The primary objective of our multicentric retrospective study was to evaluate the prognostic relevance of the NEC score and Rb status, assessed by immunohistochemistry in PE-treated patients with metastatic NEC.

Methods: Seven centres participated. The inclusion criteria were NEC, whatever the primary site, metastatic stage, first-line treatment with PE and tissue samples available. Rb status was determined centrally.

Results: We report multicentric data from 185 metastatic patients (37% women, median age 63). There were 108 small-cell NECs (SCNECs, 58.4%), 50 large-cell NECs (LCNECs, 27%) and 27 not otherwise specified NECs (nosNECs, 14.6%). The primary sites were the thorax (37%), gastroenteropancreatic sites (38%), unknown (15%) and other (9%). The mean Ki-67 index was 76% (range 20-100). Rb status was interpretable in 122 cases. Rb expression was lost in 74% of the cases: 84% of SCNEC vs. 60% and 63% of LCNEC and nosNEC, respectively (p = 0.016). Objective response was seen in 70% of SCNEC, 45% of LCNEC and 48% of nosNEC (p < 0.001) and in 62% of Rb-negative tumours vs. 46% of Rb-positive tumours (p = 0.3). There was no difference in median progression-free survival or overall survival (OS) as per Rb status. Age, NEC score and response to chemotherapy were the main factors associated with OS in our cohort.

Conclusion: In our series, Rb status had no prognostic impact in PE-treated metastatic patients with NEC, whereas age, NEC score and response to chemotherapy were the main factors associated with OS.

Keywords: Chemotherapy; Neuroendocrine carcinoma; Prognostic; Rb.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Carboplatin / administration & dosage
  • Carcinoma, Neuroendocrine / diagnosis
  • Carcinoma, Neuroendocrine / drug therapy
  • Carcinoma, Neuroendocrine / mortality*
  • Carcinoma, Neuroendocrine / pathology
  • Cisplatin / administration & dosage
  • Drug Administration Schedule
  • Etoposide / administration & dosage*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Retinoblastoma Binding Proteins / analysis*
  • Retinoblastoma Binding Proteins / metabolism
  • Retrospective Studies
  • Risk Assessment
  • Ubiquitin-Protein Ligases / analysis*
  • Ubiquitin-Protein Ligases / metabolism
  • Young Adult


  • Biomarkers, Tumor
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Etoposide
  • Carboplatin
  • Ubiquitin-Protein Ligases
  • Cisplatin