{"entity":{"id":"localised-adrenocortical-carcinoma","kind":"cancer","name":"Localised adrenocortical carcinoma (ENSAT stage I to III, resectable)","aka":["Resectable adrenocortical carcinoma","Early-stage ACC","Non-metastatic adrenal cortical carcinoma","Adrenocortical carcinoma after complete resection"],"tldr":"Localised adrenocortical carcinoma is adrenal cortex cancer still confined to the adrenal gland and its surroundings that surgery can remove, the only treatment that cures it. Afterwards the adrenal-specific drug mitotane is given to patients whose tumour has a high risk of returning, judged by the Ki-67 index and whether it was completely removed, while low-risk patients are watched.","summary":"Adrenocortical carcinoma is a rare cancer of the steroid-producing adrenal cortex. About six in ten tumours secrete hormones, most often cortisol (Cushing's syndrome) or androgens (virilisation in women), and the rest are found as incidental or symptomatic masses; a full hormone work-up before surgery both establishes the diagnosis and prepares the patient for adrenal insufficiency afterwards. The Weiss score confirms malignancy on pathology, the Ki-67 index grades it, and the ENSAT system stages it: stage I and II tumours are confined to the adrenal, stage III has invaded surrounding tissue or nodes, and stage IV has metastasised. Children with adrenocortical carcinoma nearly always carry a germline TP53 mutation, including the R337H founder mutation of southern Brazil, and do better than adults when the tumour is resected; adults are tested for Lynch syndrome and Li-Fraumeni syndrome.\n\nOpen adrenalectomy with en bloc removal of adherent structures and regional nodes by an experienced surgeon is the standard for suspected carcinoma; laparoscopic surgery is reserved for small tumours and tumour rupture must be avoided because it seeds the peritoneum. Even after complete resection the disease often returns, so the 2018 ESE/ENSAT guideline recommends adjuvant mitotane, the adrenolytic drug approved in 1970, for patients at high risk of recurrence (Ki-67 above 10 percent, stage III or incomplete resection), titrated to plasma levels of 14 to 20 mg/L and given for at least two years alongside hydrocortisone replacement. The ADIUVO trial (Lancet Diabetes and Endocrinology 2023) randomised low-risk patients (stage I to III, complete resection, Ki-67 of 10 percent or less) to mitotane or observation and found no benefit, so observation is now the standard for that group. Postoperative radiotherapy to the tumour bed is considered for incomplete resection, and platinum-based chemotherapy is added to mitotane for very high-risk tumours in some centres, although the randomised ADIUVO-2 trial addressing that question is still recruiting. Follow-up imaging every three months in the first years catches recurrences that can sometimes be resected again.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Adrenocortical_carcinoma","links":[{"label":"ADIUVO (Lancet Diabetes and Endocrinology 2023)","url":"https://doi.org/10.1016/S2213-8587(23)00193-6"},{"label":"ESE/ENSAT guideline 2018","url":"https://doi.org/10.1530/EJE-18-0608"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adrenocortical_carcinoma"}],"tags":["subtype-page","endocrine"],"related":["advanced-adrenocortical-carcinoma","adrenocortical","hereditary-ppgl"],"cancers":[],"sections":[],"technologies":["robotic-surgery","imrt-igrt","germline-testing","thermal-ablation","sbrt","ct","mri","fdg-pet"],"targets":["tp53"],"drugs":["mitotane","cisplatin","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["adrenalectomy","germline-vs-somatic","lymphadenectomy","staging-systems"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-adiuvo-adjuvant-mitotane-acc-lancet-diabetes-endocrinol-2023","paper-ese-ensat-adrenocortical-carcinoma-guideline-eur-j-endocrinol-2018"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"Roughly half to two thirds of adrenocortical carcinomas are found without distant metastases, often as a large adrenal mass causing Cushing's syndrome or virilisation, or incidentally on a scan; recurrence after surgery is nonetheless common.","subtypes":["ENSAT stage I to II adrenocortical carcinoma (confined to the adrenal)","ENSAT stage III adrenocortical carcinoma (local invasion or regional nodes)","Low-risk resected adrenocortical carcinoma (Ki-67 of 10 percent or less, R0; observation after ADIUVO)","High-risk resected adrenocortical carcinoma (Ki-67 above 10 percent, stage III or R1; adjuvant mitotane)","Cortisol-secreting adrenocortical carcinoma (Cushing's syndrome; steroid replacement after surgery)","Paediatric adrenocortical carcinoma (germline TP53, virilising, better prognosis when localised)"],"biomarkers":["Weiss score of three or more (malignancy)","Ki-67 index (10 and 20 percent thresholds for risk)","ENSAT stage and resection status","Hormone profile (cortisol, DHEAS, androgens, aldosterone, steroid precursors)","Urinary steroid metabolomics (diagnosis, emerging)","Germline TP53 in all children; Lynch syndrome testing in adults","Plasma mitotane level (14 to 20 mg/L target)"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Hormone work-up, contrast CT or MRI of the adrenal, chest CT and FDG-PET; no biopsy of a resectable adrenal mass; germline testing.","refs":["ct","mri","fdg-pet","germline-testing","germline-vs-somatic"],"guideline":{"version":"ESE/ENSAT guideline on adrenocortical carcinoma 2018","url":"https://doi.org/10.1530/EJE-18-0608"}},{"setting":"Resectable disease","approach":"Open adrenalectomy with en bloc resection of adherent structures and locoregional lymphadenectomy by an experienced surgeon; laparoscopic surgery only for small tumours; perioperative hydrocortisone for cortisol-secreting tumours.","refs":["adrenalectomy","lymphadenectomy","robotic-surgery"],"guideline":{"version":"ESE/ENSAT guideline on adrenocortical carcinoma 2018","url":"https://doi.org/10.1530/EJE-18-0608"}},{"setting":"After complete resection, low risk","approach":"Observation with imaging every three months (ADIUVO showed no benefit from mitotane).","refs":["mitotane","ct"],"guideline":{"version":"ESE/ENSAT guideline on adrenocortical carcinoma 2018","url":"https://doi.org/10.1530/EJE-18-0608"}},{"setting":"After resection, high risk","approach":"Adjuvant mitotane titrated to 14 to 20 mg/L for at least two years with glucocorticoid replacement; tumour-bed radiotherapy after incomplete resection; platinum-based chemotherapy considered for very high-risk tumours (ADIUVO-2).","refs":["mitotane","imrt-igrt","etoposide","cisplatin"],"guideline":{"version":"ESE/ENSAT guideline on adrenocortical carcinoma 2018","url":"https://doi.org/10.1530/EJE-18-0608"}},{"setting":"Local recurrence","approach":"Repeat resection when feasible after a disease-free interval of a year or more, with mitotane; ablation or radiotherapy for small unresectable recurrences.","refs":["adrenalectomy","thermal-ablation","sbrt","mitotane"],"guideline":{"version":"ESE/ENSAT guideline on adrenocortical carcinoma 2018","url":"https://doi.org/10.1530/EJE-18-0608"}}],"stateOfArt":["Complete open resection by an experienced surgeon remains the only cure.","ADIUVO showed that low-risk patients can be spared mitotane.","Ki-67 and resection status now steer adjuvant treatment more than stage alone."],"history":[{"year":1960,"title":"Mitotane (o,p'-DDD) first used for adrenocortical carcinoma","refs":["mitotane"]},{"year":1970,"title":"Mitotane approved in the United States","refs":["mitotane"]},{"year":2007,"title":"Retrospective Italian-German study associates adjuvant mitotane with longer recurrence-free survival","refs":["mitotane"]},{"year":2009,"title":"ENSAT staging system published","refs":["staging-systems"]},{"year":2018,"title":"ESE/ENSAT guideline sets Ki-67 and resection status as the basis for adjuvant mitotane","refs":["mitotane"]},{"year":2023,"title":"ADIUVO: no benefit from adjuvant mitotane in low-risk resected disease","refs":["mitotane"]}],"pipeline":["mitotane","cisplatin","etoposide"],"openProblems":["Whether adjuvant chemotherapy adds to mitotane in high-risk disease awaits ADIUVO-2.","Mitotane is slow to reach therapeutic levels and causes neurological and gastrointestinal toxicity in many patients.","Adrenal incidentalomas are common and distinguishing early carcinoma from adenoma on imaging is imperfect.","Surgical expertise is concentrated in few centres."],"parent":"adrenocortical"},"route":"/cancers/localised-adrenocortical-carcinoma/","neighbours":{"cancer":[{"id":"adrenocortical","kind":"cancer","name":"Adrenocortical carcinoma","route":"/cancers/adrenocortical/"},{"id":"advanced-adrenocortical-carcinoma","kind":"cancer","name":"Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)","route":"/cancers/advanced-adrenocortical-carcinoma/"},{"id":"hereditary-ppgl","kind":"cancer","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/cancers/hereditary-ppgl/"}],"technology":[{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"thermal-ablation","kind":"technology","name":"Thermal ablation (RFA, microwave, cryo)","route":"/technologies/thermal-ablation/"}],"target":[{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"mitotane","kind":"drug","name":"Mitotane","route":"/drugs/mitotane/"}],"term":[{"id":"adrenalectomy","kind":"term","name":"Adrenalectomy","route":"/terms/adrenalectomy/"},{"id":"staging-systems","kind":"term","name":"Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)","route":"/terms/staging-systems/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","route":"/terms/lymphadenectomy/"}],"paper":[{"id":"paper-adiuvo-adjuvant-mitotane-acc-lancet-diabetes-endocrinol-2023","kind":"paper","name":"ADIUVO: adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma","route":"/key-papers/paper-adiuvo-adjuvant-mitotane-acc-lancet-diabetes-endocrinol-2023/"},{"id":"paper-ese-ensat-adrenocortical-carcinoma-guideline-eur-j-endocrinol-2018","kind":"paper","name":"European Society of Endocrinology and ENSAT clinical practice guidelines on the management of adrenocortical carcinoma in adults","route":"/key-papers/paper-ese-ensat-adrenocortical-carcinoma-guideline-eur-j-endocrinol-2018/"}]}}