S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

Yasir S Elhassan, Barbara Altieri, Sarah Berhane, Deborah Cosentini, Anna Calabrese, Magalie Haissaguerre, Darko Kastelan, Maria Candida Barisson Villares Fragoso, Jerome Bertherat, Abir Al Ghuzlan, H R Haak, Maria Boudina, Letizia Canu, Paola Loli, Mark Sherlock, Otilia Kimpel, Marta Laganà, Alice J Sitch, Matthias Kroiss, Wiebke ArltMassimo Terzolo, Alfredo Berruti, Jon Deeks, Rosella Libe, Martin Fassnacht, Cristina L Ronchi

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Abstract

Objective: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC.

Design: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy.

Methods: The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0; 3 = 1; 4 = 2), grade (Ki67 index 0-9% = 0; 10-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3), age (<50 years = 0; ≥50 years = 1), symptoms (no = 0; yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic.

Results: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5.

Conclusion: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

Original languageEnglish
Pages (from-to)25-36
Number of pages12
JournalEuropean Journal of Endocrinology
Volume186
Issue number1
Early online date30 Nov 2021
DOIs
Publication statusPublished - 1 Jan 2022

Keywords

  • Adrenal Cortex Neoplasms/diagnosis
  • Adrenalectomy
  • Adrenocortical Carcinoma/diagnosis
  • Adult
  • Aged
  • Aged, 80 and over
  • Diagnostic Techniques, Endocrine
  • Disease Progression
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local/diagnosis
  • Neoplasm Staging
  • Prognosis
  • Research Design
  • Retrospective Studies
  • Survival Analysis

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