Localised adrenocortical carcinoma (ENSAT stage I to III, resectable)
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Check before combiningKidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Check before combiningKidneys: Etoposide
Reduce to 75% for CrCl 15-50.
See all on the product pages:CisplatinEtoposide·Printable cards in the navigator
Anatomy and lymph node drainage
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)
- Bladder muscle wall (muscle-invasive)
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)
- Developing kidney (Wilms tumour)
- Nodes: renal hilar
- Nodes: para-aortic and paracaval
- Nodes: obturator and iliac (bladder)
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
- Renal cortex (RCC)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)
- Bladder muscle wall (muscle-invasive)
- Adrenal cortexENSAT 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)
- Adrenal medulla and sympathetic chain (neuroblastoma)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)
- Developing kidney (Wilms tumour)
- renal hilar
- para-aortic and paracaval
- obturator and iliac (bladder)
Same organ: Non-muscle-invasive bladder cancer, Muscle-invasive and advanced bladder cancer, Bladder & urothelial cancer, Clear cell renal cell carcinoma, Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Low-risk neuroblastoma (INRG very low and low risk, including stage MS), Intermediate-risk neuroblastoma, High-risk neuroblastoma, Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Urethral cancer, Penile cancer, Localised penile cancer (organ-confined, node-negative), Node-positive and metastatic penile cancer, Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable), Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127), Metastatic pheochromocytoma and paraganglioma
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.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Hormone work-up, contrast CT or MRI of the adrenal, chest CT and FDG-PET; no biopsy of a resectable adrenal mass; germline testing.
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.
Observation with imaging every three months (ADIUVO showed no benefit from mitotane).
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).
Repeat resection when feasible after a disease-free interval of a year or more, with mitotane; ablation or radiotherapy for small unresectable recurrences.
Subtypes & biomarkers
top- 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)
- 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)
How often this target appears
- 1960Mitotane (o,p'-DDD) first used for adrenocortical carcinoma
- 1970Mitotane approved in the United States
- 2007Retrospective Italian-German study associates adjuvant mitotane with longer recurrence-free survival
- 2009ENSAT staging system published
- 2018ESE/ENSAT guideline sets Ki-67 and resection status as the basis for adjuvant mitotane
- 2023ADIUVO: no benefit from adjuvant mitotane in low-risk resected disease
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 12 changes by month →- 2026-09-18This recordLocalised adrenocortical carcinoma (ENSAT stage I to III, resectable)Facts on this page last checked
When this page itself was last checked or edited.
- 2023MilestoneMitotaneADIUVO: no benefit from adjuvant mitotane in low-risk resected disease
A milestone in how this cancer is treated.
- 2018GuidelineLocalised adrenocortical carcinoma (ENSAT stage I to III, resectable)Guideline ESE/ENSAT guideline on adrenocortical carcinoma 2018: After complete resection, low risk
Observation with imaging every three months (ADIUVO showed no benefit from mitotane).
- 2018GuidelineLocalised adrenocortical carcinoma (ENSAT stage I to III, resectable)Guideline ESE/ENSAT guideline on adrenocortical carcinoma 2018: 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).
- 2018GuidelineLocalised adrenocortical carcinoma (ENSAT stage I to III, resectable)Guideline ESE/ENSAT guideline on adrenocortical carcinoma 2018: 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.
- 2018GuidelineLocalised adrenocortical carcinoma (ENSAT stage I to III, resectable)Guideline ESE/ENSAT guideline on adrenocortical carcinoma 2018: 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.
What is in development for Localised adrenocortical carcinoma (ENSAT stage I to III, resectable), drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
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.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- IMRT / IGRT (modern external beam)Standard of care
- Robotic & minimally invasive surgeryStandard of care
- SBRT / SABR (stereotactic radiotherapy)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
Adrenal incidentalomas are common and distinguishing early carcinoma from adenoma on imaging is imperfect.
Surgical expertise is concentrated in few centres.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Guangzhou · hospital | China | none recorded | 0 | 1,245 | 12,931 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - | ||
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Localised adrenocortical carcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Localised adrenocortical carcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Weiss score of three or more, Ki-67 index, ENSAT stage and resection status, Hormone profile, Urinary steroid metabolomics), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include ENSAT stage I to II adrenocortical carcinoma, ENSAT stage III adrenocortical carcinoma, Low-risk resected adrenocortical carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Why: Guideline options include: Hormone work-up, contrast CT or MRI of the adrenal, chest CT and FDG-PET; no biopsy of a resectable adrenal mass; germline testing.
Resectable disease
- For my situation (resectable disease), which of the standard options do you recommend and why?Why: Guideline options include: 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.
After complete resection, low risk
- For my situation (after complete resection, low risk), which of the standard options do you recommend and why?Why: Guideline options include: Observation with imaging every three months (ADIUVO showed no benefit from mitotane).
- Am I a candidate for Mitotane, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
After resection, high risk
- For my situation (after resection, high risk), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- Am I a candidate for Mitotane, Etoposide, Cisplatin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Local recurrence
- For my situation (local recurrence), which of the standard options do you recommend and why?Why: Guideline options include: Repeat resection when feasible after a disease-free interval of a year or more, with mitotane; ablation or radiotherapy for small unresectable recurrences.
- Am I a candidate for Mitotane, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Mitotane, Cisplatin, Etoposide?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether adjuvant chemotherapy adds to mitotane in high-risk disease awaits ADIUVO-2”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Mitotane is slow to reach therapeutic levels and causes neurological and gastrointestinal toxicity in many patients”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Localised adrenocortical carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
12targets
2drugs
3companies
1terms
4key papers
2Patients with completely resected, low-proliferation adrenocortical carcinoma can be spared adjuvant mitotane; it remains recommended for higher-risk disease on retrospective evidence.
The standard-of-care rows on both adrenocortical carcinoma pages, from who gets mitotane after surgery to the EDP-M regimen, follow this guideline.
Latest papers
topQuery for this cancer: (TITLE:"Localised adrenocortical carcinoma" OR ABSTRACT:"Localised adrenocortical carcinoma" OR TITLE:"ENSAT stage I to III, resectable" OR ABSTRACT:"ENSAT stage I to III, resectable" OR TITLE:"Resectable adrenocortical carcinoma" OR ABSTRACT:"Resectable adrenocortical carcinoma" OR TITLE:"Early-stage ACC" OR ABSTRACT:"Early-stage ACC" OR TITLE:"Non-metastatic adrenal cortical carcinoma" OR ABSTRACT:"Non-metastatic adrenal cortical carcinoma" OR TITLE:"Adrenocortical carcinoma after complete resection" OR ABSTRACT:"Adrenocortical carcinoma after complete resection") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Localised adrenocortical carcinoma (ENSAT stage I to III, resectable), not a curated reading list.
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