Clinical predictors of outcome in advanced adrenocortical carcinoma: a multicenter international ENSAT study.
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Authors
Mangone A.
Altieri B.
Ferrante E.
Bancos I.
Luconi M.
Ziolkowska B.
Nekic A.B.
Libe R.
Ceccato F.
Pittaway J.F.H.
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2026
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Article
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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. Copyright © 2026 The Author(s).
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European Journal of Endocrinology
Volume
194
Issue
3