Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;113(4):457-469.
doi: 10.1159/000528186. Epub 2022 Nov 23.

Prognostic Factors across Poorly Differentiated Neuroendocrine Neoplasms: A Pooled Analysis

Giovanni Centonze  1 , Patrick Maisonneuve  2 , Natalie Prinzi  3 , Sara Pusceddu  3 , Luca Albarello  4 , Eleonora Pisa  5 , Massimo Barberis  5 , Alessandro Vanoli  6   7 , Paola Spaggiari  8 , Paola Bossi  8 , Laura Cattaneo  1 , Giovanna Sabella  1 , Enrico Solcia  6   7 , Stefano La Rosa  9 , Federica Grillo  10 , Giovanna Tagliabue  11 , Aldo Scarpa  12   13 , Mauro Papotti  14 , Marco Volante  14 , Alessandro Mangogna  15 , Alessandro Del Gobbo  16 , Stefano Ferrero  16   17 , Luigi Rolli  18 , Elisa Roca  19 , Luisa Bercich  20 , Mauro Benvenuti  21 , Luca Messerini  22 , Frediano Inzani  23 , Giancarlo Pruneri  24 , Adele Busico  24 , Federica Perrone  24 , Elena Tamborini  24 , Alessio Pellegrinelli  25 , Ketevani Kankava  26 , Alfredo Berruti  27   28 , Ugo Pastorino  18 , Nicola Fazio  29 , Fausto Sessa  9 , Carlo Capella  9 , Guido Rindi  30   31 , Massimo Milione  1
Affiliations
Free article

Prognostic Factors across Poorly Differentiated Neuroendocrine Neoplasms: A Pooled Analysis

Giovanni Centonze et al. Neuroendocrinology. 2023.
Free article

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Neuroendocrinology. 2024;114(6):602. doi: 10.1159/000538574. Epub 2024 Apr 8. Neuroendocrinology. 2024. PMID: 38588655 No abstract available.

Abstract

Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated.

Methods: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF).

Results: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal site (n = 83, 20%; 66 gastric, 79%) and pancreas (n = 42, 10%). The Ki-67 index was the most relevant predictor, followed by morphology (pure or mixed/combined NECs), stage, and site. The predicted RSF response for survival at 1, 2, or 3 years showed decreasing survival with increasing Ki-67, pure NEC morphology, stage III-IV, and colorectal NEC disease. Patients with Ki-67 <55% and mixed/combined morphology had better survival than those with pure morphology. Morphology pure or mixed/combined became irrelevant in NEC survival when Ki-67 was ≥55%. The prognosis of metastatic patients who did not receive any treatment tended to be worse compared to that of the treated group. The prognostic impact of Rb1 immunolabeling appears to be limited when multiple risk factors are simultaneously assessed.

Conclusion: The most effective parameters to predict OS for NEC patients could be Ki-67, pure or mixed/combined morphology, stage, and site.

Keywords: Ki-67; Neuroendocrine neoplasm; PD-NEC; Stage; Survival.

PubMed Disclaimer

Publication types