# Localised adrenocortical carcinoma (ENSAT stage I to III, resectable)

Source: https://onco.cc/cancers/localised-adrenocortical-carcinoma/  
OnCo record `localised-adrenocortical-carcinoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Open 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Resectable adrenocortical carcinoma; Early-stage ACC; Non-metastatic adrenal cortical carcinoma; Adrenocortical carcinoma after complete resection
- Tags: subtype-page; endocrine
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/localised-adrenocortical-carcinoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#treating-it [5 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#evidence [2 trials, 2 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#science [2 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/localised-adrenocortical-carcinoma/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/localised-adrenocortical-carcinoma/#living-with-it [19 questions, 5 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/localised-adrenocortical-carcinoma/coming/ [3 medicines, 2 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/localised-adrenocortical-carcinoma/data/ [26 connected records]

## Standard of care

- Diagnosis and staging: Hormone work-up, contrast CT or MRI of the adrenal, chest CT and FDG-PET; no biopsy of a resectable adrenal mass; germline testing. ([CT (computed tomography)](https://onco.cc/technologies/ct/), [MRI](https://onco.cc/technologies/mri/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/))
- Resectable disease: 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. ([Adrenalectomy](https://onco.cc/terms/adrenalectomy/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/))
- After complete resection, low risk: Observation with imaging every three months (ADIUVO showed no benefit from mitotane). ([Mitotane](https://onco.cc/drugs/mitotane/), [CT (computed tomography)](https://onco.cc/technologies/ct/), [ADIUVO](https://onco.cc/trials/adiuvo/))
- After resection, high risk: 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). ([Mitotane](https://onco.cc/drugs/mitotane/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Etoposide](https://onco.cc/drugs/etoposide/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [ADIUVO](https://onco.cc/trials/adiuvo/), [ADIUVO-2](https://onco.cc/trials/adiuvo-2/))
- Local recurrence: Repeat resection when feasible after a disease-free interval of a year or more, with mitotane; ablation or radiotherapy for small unresectable recurrences. ([Adrenalectomy](https://onco.cc/terms/adrenalectomy/), [Thermal ablation (RFA, microwave, cryo)](https://onco.cc/technologies/thermal-ablation/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Mitotane](https://onco.cc/drugs/mitotane/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Adrenocortical_carcinoma
- ADIUVO (Lancet Diabetes and Endocrinology 2023): https://doi.org/10.1016/S2213-8587(23)00193-6
- ESE/ENSAT guideline 2018: https://doi.org/10.1530/EJE-18-0608
- Wikipedia: https://en.wikipedia.org/wiki/Adrenocortical_carcinoma

## Connected records

- cancers: [Adrenocortical carcinoma](https://onco.cc/cancers/adrenocortical/), [Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)](https://onco.cc/cancers/advanced-adrenocortical-carcinoma/), [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/)
- technologies: [CT (computed tomography)](https://onco.cc/technologies/ct/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Thermal ablation (RFA, microwave, cryo)](https://onco.cc/technologies/thermal-ablation/)
- targets: [TP53](https://onco.cc/targets/tp53/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Mitotane](https://onco.cc/drugs/mitotane/)
- terms: [Adrenalectomy](https://onco.cc/terms/adrenalectomy/), [Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)](https://onco.cc/terms/staging-systems/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/)
- key papers: [ADIUVO: adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma](https://onco.cc/key-papers/paper-adiuvo-adjuvant-mitotane-low-grade-acc-terzolo-lancet-diabetes-endocrinol-2023/), [European Society of Endocrinology and ENSAT clinical practice guidelines on the management of adrenocortical carcinoma in adults](https://onco.cc/key-papers/paper-ese-ensat-adrenocortical-carcinoma-guideline-eur-j-endocrinol-2018/)
- trials: [ADIUVO](https://onco.cc/trials/adiuvo/), [ADIUVO-2](https://onco.cc/trials/adiuvo-2/)

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JSON: https://onco.cc/api/v1/entities/localised-adrenocortical-carcinoma.json