Clinical predictors of outcome in advanced adrenocortical carcinoma: a multicenter international ENSAT study.
Mangone, Alessandra Altieri, Barbara Ferrante, Emanuele Bancos, Irina Luconi, Michaela Ziółkowska, Barbara Nekić, Anja Barač Libe, Rossella Ceccato, Filippo Pittaway, James F H
Mangone, Alessandra
Altieri, Barbara
Ferrante, Emanuele
Bancos, Irina
Luconi, Michaela
Ziółkowska, Barbara
Nekić, Anja Barač
Libe, Rossella
Ceccato, Filippo
Pittaway, James F H
Abstract
OBJECTIVE: Advanced adrenocortical carcinoma (ACC) is treated with mitotane alone or combined with cytotoxic chemotherapy, yet outcomes remain poor and prognostic models in this setting are lacking. This study aimed to evaluate the prognostic value of clinical parameters in a large cohort of patients with advanced ACC undergoing systemic therapy.
METHODS: Multicenter, international cohort study investigating 418 patients with advanced ACC (61.5% = women, median age = 52 years) from 11 centers. Patients received mitotane monotherapy (n = 161), etoposide + doxorubicin + cisplatin ± mitotane (n = 178), or second-line regimens (gemcitabine + capecitabine ± mitotane or temozolomide + mitotane, n = 79). Variables included age, cortisol excess, performance status (ECOG-PS), tumor burden, and neutrophil-to-lymphocyte ratio (NLR) at start of therapy. Outcomes were overall survival (OS), time to progression (TTP), and best objective response.
RESULTS: Tumor burden, cortisol excess, ECOG-PS, and NLR ≥5 independently predicted shorter OS (hazard ratio [HR] 1.55-2.68). We developed an integrated ENSAT Risk Score for Advanced ACC combining these variables: tumor burden (0-2), cortisol excess (0/1), ECOG-PS (0-2), and NLR (0/1). A score >2 (poor-risk) was significantly associated with worse OS and TTP across all treatment groups (HRs for OS: 3.05-3.96; TTP: 2.53-3.08). It also predicted poorer response to mitotane (P < .01) and second-line therapies (P = .04).
CONCLUSIONS: The ENSAT Risk Score for Advanced ACC is a practical, prognostic tool for patients with advanced ACC receiving systemic therapy. Based on accessible clinical and biochemical markers, it can support treatment decisions and facilitate informed discussions in routine care.
MIDER Authors
Date
2026-03-04
Type
Article
Subject
Chemotherapy, predictors
Collections
Citation
Mangone A, Altieri B, Ferrante E, Bancos I, Luconi M, Ziółkowska B, Nekić AB, Libe R, Ceccato F, Pittaway JFH, Laganà M, Di Dalmazi G, Peverelli E, Kimpel O, Fard BB, Canu L, Kotecka-Blicharz A, Kastelan D, Bouys L, Tizianel I, Bennett G, Schauer MP, Elhassan YS, Detomas M, Zanatta L, Sadiq M, Mantovani G, Ronchi CL. Clinical predictors of outcome in advanced adrenocortical carcinoma: a multicenter international ENSAT study. Eur J Endocrinol. 2026 Mar 4;194(3):381-392. doi: 10.1093/ejendo/lvag046.
Journal / Source Title
European Journal of Endocrinology
DOI
10.1093/ejendo/lvag046
PMID
41790725
Publisher
Oxford University Press
Publisher’s URL
https://eje.bioscientifica.com/