{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:13:55Z","timestamp":1775121235851,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy, for which population-level evidence regarding prognostic factors and survival conditions is limited. The available data mostly represent single-institution series, limiting their applicability. This study, therefore, assesses clinicopathological features and determines independent predictive variables of overall survival (OS) in patients with ACC using a population-based cohort. Methods: This retrospective observational cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) Program between 2000 and 2022, initially identifying 1176 patients with ACC. Adult patients (\u226518 years) with histologically confirmed ACC were identified using ICD-O-3 histology code 8370\/3 and primary site code C74.0. Cases with zero-month survival, missing survival data, or identified only through autopsy or death certificate were excluded. To ensure dataset harmonization, patients with missing or indeterminate tumor grade and unknown stage were also excluded. After applying these inclusion and exclusion criteria, the final analytic cohort consisted of 267 patients. Data on demographic factors, stage of the disease, and treatment (surgery, chemotherapy, radiotherapy) were extracted. OS was evaluated using the Kaplan\u2013Meier method, and independent prognostic factors were identified using Cox proportional hazards regression analysis. Results: The median OS was 54 months [95% confidence intervals (CI): 36\u201385]. The estimated 1-, 3-, and 5-year OS rates were 77%, 57%, and 48%, respectively. Survival differed significantly according to tumor grade, stage, and surgical treatment. In multivariable Cox regression analysis, increasing age [Hazard ratio (HR): 1.03, 95% CI: 1.02\u20131.04; p &lt; 0.001], high tumor grade (HR: 2.21, 95% CI: 1.43\u20133.41; p &lt; 0.001), and distant-stage disease (HR: 3.24, 95% CI: 1.95\u20135.38; p &lt; 0.001) were independently associated with an increased risk of mortality, whereas surgical treatment was associated with improved survival (HR 0.53, 95% CI 0.30\u20130.93; p = 0.028). Chemotherapy and radiotherapy were not significantly associated with mortality. Conclusions: In this SEER-based cohort of patients with adrenocortical carcinoma, older age, high tumor grade, and distant-stage disease were independently associated with worse OS, whereas documented receipt of surgery was associated with longer OS. Treatment-related associations should be interpreted cautiously in view of the inherent limitations of registry-based data. Further prospective multicenter studies are needed to confirm these findings.<\/jats:p>","DOI":"10.3390\/cancers18071103","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:57:24Z","timestamp":1774864644000},"page":"1103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathologic Determinants of Overall Survival in Adrenocortical Carcinoma: A SEER-Based Population Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-4445","authenticated-orcid":false,"given":"An\u0131l","family":"Y\u0131ld\u0131z","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Ba\u015fak\u015fehir \u00c7am ve Sakura City Hospital, Ba\u015fak\u015fehir Neighborhood, G-434 Street, No: 2L, 34480 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-3291","authenticated-orcid":false,"given":"Oguzcan","family":"K\u0131n\u0131ko\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kartal Dr. Lutfi Kirdar Education and Research Hospital, 34865 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1210\/er.2013-1029","article-title":"Adrenocortical carcinoma","volume":"35","author":"Else","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4551","DOI":"10.1210\/jc.2013-3020","article-title":"Update in adrenocortical carcinoma","volume":"98","author":"Fassnacht","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","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."},{"key":"ref_4","first-page":"383","article-title":"Oncocytic Adrenocortical Carcinoma in a Young Patient","volume":"18","author":"Singh","year":"2022","journal-title":"Acta Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S2213-8587(24)00378-4","article-title":"Adrenocortical carcinoma: A practical guide for clinicians","volume":"13","author":"Fassnacht","year":"2025","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Flauto, F., Ferone, G., De Martino, M.C., Pivonello, R., Colao, A., and Damiano, V. (2025). The management of adrenocortical carcinoma in the era of precision medicine. Crit. Rev. Oncol. Hematol., 214.","DOI":"10.1016\/j.critrevonc.2025.104839"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"vii131","DOI":"10.1093\/annonc\/mds231","article-title":"Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"23","author":"Berruti","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s003450050101","article-title":"Adrenocortical carcinoma","volume":"17","author":"Schulick","year":"1999","journal-title":"World J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nastos, C., Papaconstantinou, D., Paspala, A., Pararas, N., Vryonidou, A., Pikouli, A., Chronopoulou, E., Lechou, A., Peppa, M., and Pikoulis, E. (2024). The impact of adrenocortical carcinoma hormone secreting status as a predictor of poor survival: A systematic review and meta-analysis. Langenbecks Arch. Surg., 409.","DOI":"10.1007\/s00423-024-03507-5"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yeoh, P., Czuber-Dochan, W., Aylwin, S., and Sturt, J. (2022). Lived experience of people with adrenocortical carcinoma and associated adrenal insufficiency. Endocrinol. Diabetes Metab., 5.","DOI":"10.1002\/edm2.341"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.radcr.2021.03.006","article-title":"Non-functioning adrenocortical carcinoma","volume":"16","author":"Lenh","year":"2021","journal-title":"Radiol. Case Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Libe, R. (2015). Adrenocortical carcinoma (ACC): Diagnosis, prognosis, and treatment. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00045"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Choi, Y.M., Kwon, H., Jeon, M.J., Sung, T.Y., Hong, S.J., Kim, T.Y., Kim, W.B., Shong, Y.K., Lee, J.L., and Song, D.E. (2016). Clinicopathological Features Associated with the Prognosis of Patients with Adrenal Cortical Carcinoma: Usefulness of the Ki-67 Index. Medicine, 95.","DOI":"10.1097\/MD.0000000000003736"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00428-025-04278-0","article-title":"Diagnosis and grading of adrenal cortical carcinoma","volume":"488","author":"Duregon","year":"2026","journal-title":"Virchows Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44955","DOI":"10.18632\/oncotarget.5831","article-title":"Conditional survival among patients with adrenal cortical carcinoma determined using a national population-based surveillance, epidemiology, and end results registry","volume":"6","author":"Xiao","year":"2015","journal-title":"Oncotarget"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/jso.26845","article-title":"Surgical resection for adrenocortical carcinoma: Current trends affecting survival","volume":"125","author":"Shah","year":"2022","journal-title":"J. Surg. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/00000478-198903000-00004","article-title":"Pathologic features of prognostic significance in adrenocortical carcinoma","volume":"13","author":"Weiss","year":"1989","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shariq, O.A., and McKenzie, T.J. (2021). Adrenocortical carcinoma: Current state of the art, ongoing controversies, and future directions in diagnosis and treatment. Ther. Adv. Chronic Dis., 12.","DOI":"10.1177\/20406223211033103"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gaillard, M., Razafinimanana, M., Challine, A., Araujo, R.L.C., Libe, R., Sibony, M., Barat, M., Bertherat, J., Dousset, B., and Fuks, D. (2023). Laparoscopic or Open Adrenalectomy for Stage I-II Adrenocortical Carcinoma: A Retrospective Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113698"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kiesewetter, B., Riss, P., Scheuba, C., Mazal, P., Kretschmer-Chott, E., Haug, A., and Raderer, M. (2021). Management of adrenocortical carcinoma: Are we making progress?. Ther. Adv. Med. Oncol., 13.","DOI":"10.1177\/17588359211038409"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ruggiero, E., Tizianel, I., Caccese, M., Lombardi, G., Pambuku, A., Zagonel, V., Scaroni, C., Formaglio, F., and Ceccato, F. (2022). Advanced Adrenocortical Carcinoma: From Symptoms Control to Palliative Care. Cancers, 14.","DOI":"10.3390\/cancers14235901"},{"key":"ref_22","first-page":"62","article-title":"Role of Mitotane in Adrenocortical Carcinoma\u2014Review and State of the art","volume":"14","author":"Paragliola","year":"2018","journal-title":"Eur. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40487-025-00327-5","article-title":"Oncological Management of Adrenocortical Carcinoma: An Update and Critical Review","volume":"13","author":"Rowell","year":"2025","journal-title":"Oncol. Ther."},{"key":"ref_24","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"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1097\/PAS.0000000000000749","article-title":"The Surveillance, Epidemiology, and End Results (SEER) Program and Pathology: Toward Strengthening the Critical Relationship","volume":"40","author":"Duggan","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/jncimonographs\/lgae022","article-title":"The SEER Program\u2019s evolution: Supporting clinically meaningful population-level research","volume":"2024","author":"Penberthy","year":"2024","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hallanger-Johnson, J.E. (2020). Systemic therapy for adrenocortical carcinoma: A review. AME Med. J., 5.","DOI":"10.21037\/amj.2020.01.07"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4097\/kja.19087","article-title":"Multicollinearity and misleading statistical results","volume":"72","author":"Kim","year":"2019","journal-title":"Korean J. Anesthesiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Flauto, F., De Martino, M.C., Vitiello, C., Pivonello, R., Colao, A., and Damiano, V. (2024). A Review on Mitotane: A Target Therapy in Adrenocortical Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16234061"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Khosla, D., Kapoor, R., Singla, A.K., Periasamy, K., Goyal, S., Madan, R., Kumar, N., Behera, A., Singh, S.K., and Bhadada, S.K. (2023). Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma\u2014A 13-years experience from a tertiary care centre. Rare Tumors, 15.","DOI":"10.1177\/20363613231160699"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1016\/S1098-3597(05)80084-5","article-title":"Current challenges in diabetes management","volume":"7","author":"Blonde","year":"2005","journal-title":"Clin. Cornerstone"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1159\/000098011","article-title":"Rare functioning pancreatic endocrine tumors","volume":"84","author":"Salazar","year":"2006","journal-title":"Neuroendocrinology"},{"key":"ref_33","first-page":"2817","article-title":"Prognostic Factors of Adrenocortical Carcinoma: An Analysis of the Surveillance Epidemiology and End Results (SEER) Database","volume":"18","author":"Wang","year":"2017","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, T., Zeng, D., Zhou, G., Qin, L., and Qian, X. (2025). Prognostic factors and treatment outcomes in patients with adrenal cortical carcinoma: A registry-based study. Medicine, 104.","DOI":"10.1097\/MD.0000000000042831"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1210\/jc.2018-00918","article-title":"Predictors of Survival in Adrenocortical Carcinoma: An Analysis from the National Cancer Database","volume":"103","author":"Tella","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pato, E., Srougi, V., Zerbini, C., Ledesma, F.L., Tanno, F., Almeida, M.Q., Nahas, W., Latronico, A.C., Mendonca, B.B., and Chambo, J.L. (2024). Clinical and Pathological Predictors of Death for Adrenocortical Carcinoma. J. Endocr. Soc., 8.","DOI":"10.1210\/jendso\/bvad170"},{"key":"ref_37","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":"2021","journal-title":"Eur. J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"He, S., Huang, X., Zhao, P., and Zhang, P. (2022). The prognosis difference between elderly and younger patients with adrenocortical carcinoma. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1029155"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.amjsurg.2022.05.033","article-title":"Surgical outcomes and survival of adrenocortical carcinoma between children and adults","volume":"224","author":"Akinkuotu","year":"2022","journal-title":"Am. J. Surg."},{"key":"ref_40","unstructured":"Mahendraraj, K., Lau, C., Sidhu, K., and Chamberlain, R. (2016). Adrenocortical carcinoma in adults and children: A population-based outcomes study involving 1,623 patients from the surveillance, epidemiology, and end result (SEER) database (1973\u20132012). Clin. Surg., 1."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.2147\/OTT.S147352","article-title":"Primary site surgery for metastatic adrenocortical carcinoma improves survival outcomes: An analysis of a population-based database","volume":"10","author":"Wang","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Vietor, C.L., Schurink, I.J., Grunhagen, D.J., Verhoef, C., Franssen, G.J.H., Feelders, R.A., and van Ginhoven, T.M. (2025). Primary tumour resection in metastasised adrenocortical carcinoma. Endocr. Relat. Cancer, 32.","DOI":"10.1530\/ERC-24-0056"},{"key":"ref_43","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."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shekar, S., Hall, A., Pham, J., Crumbaker, M., Liu, J., Talmor, B., Sim, H.W., and Joshua, A.M. (2025). Efficacy of systemic therapy in metastatic adrenocortical carcinoma: A meta-analysis of prospective clinical trials. Endocr. Oncol., 5.","DOI":"10.1530\/EO-25-0027"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.critrevonc.2014.05.009","article-title":"Adrenocortical carcinoma: The management of metastatic disease","volume":"92","author":"Fay","year":"2014","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.clgc.2021.03.009","article-title":"Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma","volume":"19","author":"Thomas","year":"2021","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1210\/jc.2019-00029","article-title":"Adjuvant Radiation Improves Recurrence-Free Survival and Overall Survival in Adrenocortical Carcinoma","volume":"104","author":"Gharzai","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Elmali, A., Guler, O.C., Ozyigit, G., Hurmuz, P., and Onal, C. (2026). Impact of Adjuvant Radiotherapy and Mitotane on Survival in Localized Adrenocortical Carcinoma: A Retrospective Cohort Study. Int. J. Urol., 33.","DOI":"10.1111\/iju.70319"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:05:10Z","timestamp":1775117110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cancers18071103"],"URL":"https:\/\/doi.org\/10.3390\/cancers18071103","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]}}}