{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:54Z","timestamp":1791829434387,"version":"4.3.4"},"reference-count":22,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We aimed to determine time trends in incidence, treatment, and survival of patients with adrenocortical carcinoma in the Netherlands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nationwide prospective Netherlands Cancer Registry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83\u20132.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13%-25%) with a stable proportion of stage IV (40%). The 5-year survival remained stable over time for stage I-II at 65% and stage III at 35%, whereas the survival for stage IV increased from 3% in 1993 through 1996 to 11% in 2017 through 2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (P &amp;lt; .001), which was associated with increased survival (adjusted HR 0.70; 95% CI, 0.57-0.85). Multivariate Cox regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53; 95% CI, 0.43-0.65) and mitotane therapy (adjusted HR 0.73; 95% CI, 0.55\u20130.98). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy, and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The incidence of adrenocortical carcinoma is stable over time. The 5-year survival for stage I-III remained stable, whereas the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy, and mitotane therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag088","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T12:37:34Z","timestamp":1772195854000},"page":"2349-2357","source":"Crossref","is-referenced-by-count":3,"title":["Time trends in incidence, treatment, and survival of patients with adrenocortical carcinoma, a nationwide study"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-4331","authenticated-orcid":false,"given":"Rebecca V","family":"Steenaard","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]},{"name":"CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University , Maastricht 6229 HX ,","place":["The Netherlands"]},{"name":"Department of Research, Netherlands Comprehensive Cancer Organization (IKNL) , Utrecht 3511 DT ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Sofie","family":"de Wit","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Rutjens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babs","family":"van der Bruggen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Blijdorp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pleun","family":"Wouters - van Poppel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-391X","authenticated-orcid":false,"given":"Richard A","family":"Feelders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section Endocrinology, Erasmus Medical Center , Rotterdam 3015 GD ,","place":["The Netherlands"]},{"name":"Holman Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NewYork University Langone Medical Center , New York, NY 10016 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-9359","authenticated-orcid":false,"given":"Harm R","family":"Haak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, M\u00e1xima MC , Eindhoven\/Veldhoven 5504 DB ,","place":["The Netherlands"]},{"name":"CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University , Maastricht 6229 HX ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"issue":"4","key":"2026071419580206200_dgag088-B1","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-18-0608","article-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","volume":"179","author":"Fassnacht","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"11","key":"2026071419580206200_dgag088-B2","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.annonc.2020.08.2099","article-title":"Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Fassnacht","year":"2020","journal-title":"Ann Oncol"},{"issue":"1","key":"2026071419580206200_dgag088-B3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1530\/EJE-21-0510","article-title":"S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study","volume":"186","author":"Elhassan","year":"2022","journal-title":"Eur J Endocrinol"},{"issue":"11","key":"2026071419580206200_dgag088-B4","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1016\/j.ejca.2013.02.034","article-title":"Adrenocortical carcinoma: a population-based study on incidence and survival in The Netherlands since 1993","volume":"49","author":"Kerkhofs","year":"2013","journal-title":"Eur J Cancer"},{"issue":"6","key":"2026071419580206200_dgag088-B5","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.3892\/or.2014.3506","article-title":"Adrenocortical carcinoma in children: first population-based clinicopathological study with long-term follow-up","volume":"32","author":"Kerkhofs","year":"2014","journal-title":"Oncol Rep"},{"issue":"23","key":"2026071419580206200_dgag088-B6","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1200966","article-title":"Combination chemotherapy in advanced adrenocortical carcinoma","volume":"366","author":"Fassnacht","year":"2012","journal-title":"N Engl J Med"},{"issue":"7776","key":"2026071419580206200_dgag088-B7","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-019-1600-x","article-title":"The Drug Rediscovery protocol facilitates the expanded use of existing anticancer drugs","volume":"574","author":"van der Velden","year":"2019","journal-title":"Nature"},{"issue":"3","key":"2026071419580206200_dgag088-B8","doi-asserted-by":"crossref","first-page":"bvae012","DOI":"10.1210\/jendso\/bvae012","article-title":"Incidence, treatment, and survival of adrenocortical carcinoma in Denmark 2003\u20132019","volume":"8","author":"Pedersen","year":"2024","journal-title":"J Endocr Soc"},{"issue":"6","key":"2026071419580206200_dgag088-B9","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1530\/EC-20-0196","article-title":"Characteristics of adrenocortical carcinoma in South Korea: a registry-based nationwide survey","volume":"9","author":"Lim","year":"2020","journal-title":"Endocr Connect"},{"issue":"5","key":"2026071419580206200_dgag088-B10","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1210\/clinem\/dgac046","article-title":"Temporal trends in outcomes in patients with adrenocortical carcinoma: a multidisciplinary referral-center experience","volume":"107","author":"Daher","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2026071419580206200_dgag088-B11","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S2213-8587(23)00193-6","article-title":"Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study","volume":"11","author":"Terzolo","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"12","key":"2026071419580206200_dgag088-B12","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1210\/jc.2013-2281","article-title":"Comparison of two mitotane starting dose regimens in patients with advanced adrenocortical carcinoma","volume":"98","author":"Kerkhofs","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2026071419580206200_dgag088-B13","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3390\/cancers14061366","article-title":"Health-related quality of life in adrenocortical carcinoma: development of the disease-specific questionnaire ACC-QOL and results from the PROFILES registry","volume":"14","author":"Steenaard","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2026071419580206200_dgag088-B14","doi-asserted-by":"crossref","first-page":"113424","DOI":"10.1016\/j.ejca.2023.113424","article-title":"Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: a population-based study","volume":"196","author":"Debets","year":"2024","journal-title":"Eur J Cancer"},{"issue":"2","key":"2026071419580206200_dgag088-B15","doi-asserted-by":"crossref","first-page":"e240056","DOI":"10.1530\/ERC-24-0056","article-title":"Primary tumour resection in metastasised adrenocortical carcinoma","volume":"32","author":"Vietor","year":"2024","journal-title":"Endocr Relat Cancer"},{"issue":"4","key":"2026071419580206200_dgag088-B16","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3390\/cancers16040706","article-title":"The value of local therapies in advanced adrenocortical carcinoma","volume":"16","author":"Kimpel","year":"2024","journal-title":"Cancers (Basel)"},{"issue":"1","key":"2026071419580206200_dgag088-B17","first-page":"91","article-title":"Current evidence on local therapies in advanced adrenocortical carcinoma","volume":"56","author":"Kimpel","year":"2022","journal-title":"Horm Metab Res"},{"issue":"11","key":"2026071419580206200_dgag088-B18","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.3390\/cancers14112730","article-title":"Loco-regional therapies in oligometastatic adrenocortical carcinoma","volume":"14","author":"Roux","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"4","key":"2026071419580206200_dgag088-B19","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1210\/clinem\/dgab865","article-title":"Cytoreductive surgery of the primary tumor in metastatic adrenocortical carcinoma: impact on patients' survival","volume":"107","author":"Srougi","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2026071419580206200_dgag088-B20","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41416-022-02082-0","article-title":"Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma","volume":"128","author":"Kimpel","year":"2023","journal-title":"Br J Cancer"},{"issue":"Suppl 1","key":"2026071419580206200_dgag088-B21","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.4103\/jcrt.JCRT_996_15","article-title":"Adjuvant radiotherapy after surgical resection for adrenocortical carcinoma: a systematic review of observational studies and meta-analysis","volume":"15","author":"Viani","year":"2019","journal-title":"J Cancer Res Ther"},{"issue":"3","key":"2026071419580206200_dgag088-B22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3390\/biomedicines9030304","article-title":"Immunotherapy in adrenocortical carcinoma: predictors of response, efficacy, safety, and mechanisms of resistance","volume":"9","author":"Araujo-Castro","year":"2021","journal-title":"Biomedicines"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag088\/67190962\/dgag088.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/8\/2349\/67190962\/dgag088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/8\/2349\/67190962\/dgag088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:58:30Z","timestamp":1784073510000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/111\/8\/2349\/8502741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,2,28]]},"published-print":{"date-parts":[[2026,7,15]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag088","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,2,28]]}}}