{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:55:38Z","timestamp":1793498138175,"version":"4.5.0"},"reference-count":314,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>\n                    Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete\n                    <jats:italic>en bloc<\/jats:italic>\n                    resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 &gt;10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection\/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.\n                  <\/jats:p>","DOI":"10.1530\/eje-18-0608","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T12:23:30Z","timestamp":1532435010000},"page":"G1-G46","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":879,"title":["European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors"],"prefix":"10.1093","volume":"179","author":[{"given":"Martin","family":"Fassnacht","sequence":"first","affiliation":[{"name":"1Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital"},{"name":"2Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf M","family":"Dekkers","sequence":"additional","affiliation":[{"name":"3 Department of Clinical Epidemiology"},{"name":"4Department of Clinical Endocrinology and Metabolism, Leiden University Medical Centre, Leiden, the Netherlands"},{"name":"5Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Else","sequence":"additional","affiliation":[{"name":"6Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Baudin","sequence":"additional","affiliation":[{"name":"7Endocrine Oncology and Nuclear Medicine, Institut Gustave Roussy, Villejuif, France"},{"name":"8INSERM UMR 1185, Facult\u00e9 de M\u00e9decine, Le Kremlin-Bic\u00eatre, Universit\u00e9 Paris Sud, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Berruti","sequence":"additional","affiliation":[{"name":"9Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald R","family":"de Krijger","sequence":"additional","affiliation":[{"name":"10Department of Pathology, Erasmus MC University Medical Center, Rotterdam, the Netherlands"},{"name":"11Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands"},{"name":"12Department of Pathology, Reinier de Graaf Hospital, Delft, the Netherlands"},{"name":"13Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm R","family":"Haak","sequence":"additional","affiliation":[{"name":"14Department of Internal Medicine, M\u00e1xima Medical Centre, Eindhoven\/Veldhoven, the Netherlands"},{"name":"15Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, the Netherlands"},{"name":"16Division of General Internal Medicine, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Mihai","sequence":"additional","affiliation":[{"name":"17Department of Endocrine Surgery, Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Assie","sequence":"additional","affiliation":[{"name":"18Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Reference Center dor Rare Adrenal Cancers, H\u00f4pital Cochin, Assistance Publique H\u00f4pitaux de Paris, Paris, France"},{"name":"19Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1016, Centre National de la Recherche Scientifique UMR8104, Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Terzolo","sequence":"additional","affiliation":[{"name":"20Department of Clinical and Biological Sciences, Internal Medicine, San Luigi Hospital, University of Turin, Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref2131","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/00000478-198403000-00001","article-title":"Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors","volume":"8","year":"1984","journal-title":"American Journal of Surgical Pathology"},{"key":"ref571","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1210\/jc.2014-3182","article-title":"Major prognostic role of Ki67 in localized 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