OnCo
cancersCancer

Adrenocortical carcinoma

aka ACC

Adrenocortical carcinoma is a rare, aggressive cancer of the adrenal gland that often over-produces hormones. Surgery is the only cure, mitotane is the one drug specific to it (with real toxicity), and chemotherapy or immunotherapy help only a minority.

Adrenocortical carcinoma (ACC) arises from the adrenal cortex, with TP53 (germline in most childhood cases; R337H founder mutation in Brazil), CTNNB1, ZNRF3, and IGF2 overexpression as recurrent alterations, and molecular subgroups (CIMP-high, C1A) predicting outcome. Diagnosis relies on the Weiss score and Ki-67; staging on ENSAT (I-IV). Hormone excess is present in ~60% and complicates management.

Complete open adrenalectomy (R0) is the only curative treatment; adjuvant mitotane is recommended for high-risk resected disease (Ki-67 >10%, stage III, R1), while ADIUVO (2023) showed no benefit in low-risk patients. Advanced disease is treated with etoposide-doxorubicin-cisplatin plus mitotane (EDP-M, FIRM-ACT 2012: response ~23%, no OS gain over streptozocin-mitotane), with mitotane monotherapy for indolent disease. PD-1 blockade (pembrolizumab, ~15-23% response) and cabozantinib have phase 2 activity; no targeted therapy is approved. Cortisol excess is controlled with metyrapone, osilodrostat or mifepristone. Survival is ~80% for stage I-II and ~15% for stage IV.

State of the art today

  • Mitotane, an insecticide derivative from 1959, is still the only ACC-specific drug and needs therapeutic drug monitoring.
  • ADIUVO spared low-risk patients adjuvant mitotane; risk stratification by Ki-67 is now decisive.
  • Immunotherapy and cabozantinib give a minority durable benefit; no molecular target has translated.
  • Steroid metabolomics and TP53 founder-mutation screening (Brazil) are the diagnostic advances.
Who it affects

About 1-2 per million per year, with peaks in early childhood (Li-Fraumeni, TP53 R337H in southern Brazil) and in the fifth decade; half present with hormone excess (Cushing, virilisation).

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

4top
Localised (ENSAT I-III)

Open en bloc adrenalectomy by an experienced surgeon with locoregional lymphadenectomy; adjuvant mitotane for high-risk (Ki-67 >10%, stage III, R1) for 2-5 years; adjuvant radiotherapy for R1.

ESE/ENSAT guideline 2018
MitotaneIMRT / IGRT (modern external beam)
Advanced, aggressive

EDP-M (etoposide, doxorubicin, cisplatin + mitotane) ×6-8 with surgery for responders; streptozocin-mitotane second line.

NCCN · Category 2A
EtoposideDoxorubicinCisplatinMitotane
Advanced, indolent

Mitotane monotherapy (target level 14-20 mg/L) with glucocorticoid replacement; local therapies (ablation, radiotherapy) for oligometastases.

ESE/ENSAT 2018
MitotaneThermal ablation (RFA, microwave, cryo)SBRT / SABR (stereotactic radiotherapy)
Progressive after chemotherapy

Pembrolizumab, cabozantinib, gemcitabine-capecitabine; control hormone excess; clinical trials.

NCCN · Category 2B
PembrolizumabCabozantinib

Subtypes & biomarkers

top
Subtypes
  • Hormone-secreting (cortisol, androgens, mixed) vs non-functioning
  • Adult ACC (sporadic; Lynch, Li-Fraumeni, MEN1 associations)
  • Paediatric ACC (TP53 germline, often virilising, better prognosis if localised)
  • Oncocytic, myxoid and sarcomatoid variants
  • Molecular : CIMP-high / C1A (poor) vs C1B (better)
Biomarkers clinicians test
  • Weiss score ≥3, Ki-67 index (>10% and >20% thresholds)
  • ENSAT stage and R status
  • Hormone work-up (cortisol, DHEAS, androgens, aldosterone, precursors)
  • Germline TP53 (all children), Lynch syndrome testing
  • Urinary steroid metabolomics (diagnosis, emerging)
  • MSI/TMB (rare; immunotherapy)

Target prevalence in this cancer

History

8top
  1. 1959Mitotane (o,p'-DDD) first used in ACC (Bergenstal)
    Mitotane
  2. 1984Weiss histologic criteria
  3. 2007Adjuvant mitotane associated with longer recurrence-free survival (Terzolo, NEJM)
    Mitotane
  4. 2009ENSAT staging
  5. 2012FIRM-ACT: EDP-M vs streptozocin-mitotane (NEJM)
    EtoposideDoxorubicinCisplatinMitotane
  6. 2016TCGA/ENSAT genomic classification of ACC (Zheng, Cancer Cell)
  7. 2019Pembrolizumab phase 2 in ACC (Raj, JCO)
    Pembrolizumab
  8. 2023ADIUVO: no benefit of adjuvant mitotane in low-risk disease
    Mitotane

Pipeline

3top
ApprovedSmall-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)
Cabozantinib · Cabometyx
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Not mapped hereAdrenolytic agent (DDD derivative)
Mitotane · Lysodren

Open problems

  • No targeted therapy despite defined genomic subgroups.
  • Mitotane toxicity and narrow therapeutic window.
  • Hormone excess drives morbidity and immunosuppression (cortisol blunts immunotherapy).
  • Rarity: FIRM-ACT took 8 years and 40 centres for 300 patients.

Trials

top

Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Adrenocortical carcinoma
condition: Adrenocortical carcinoma
Open on ClinicalTrials.gov →

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

top
Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

top
Bring to your appointment

Questions to ask your oncologist about Adrenocortical carcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example Weiss score ≥3, Ki-67 index, ENSAT stage and R status, Hormone work-up, Germline TP53, Lynch syndrome testing, Urinary steroid metabolomics), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Hormone-secretingvs non-functioning, Adult ACC, Paediatric ACC.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Localised (ENSAT I-III)

  1. For my situation (localised (ensat i-iii)), which of the standard options do you recommend and why?
    Why: Guideline options include: Open en bloc adrenalectomy by an experienced surgeon with locoregional lymphadenectomy; adjuvant mitotane for high-risk (Ki-67 >10%, stage III, R1) for 2-5 years; adjuvant radiotherapy for R1.
  2. 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.

Advanced, aggressive

  1. For my situation (advanced, aggressive), which of the standard options do you recommend and why?
    Why: Guideline options include: EDP-M (etoposide, doxorubicin, cisplatin + mitotane) ×6-8 with surgery for responders; streptozocin-mitotane second line.
  2. Am I a candidate for Etoposide, Doxorubicin, Cisplatin or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Advanced, indolent

  1. For my situation (advanced, indolent), which of the standard options do you recommend and why?
    Why: Guideline options include: Mitotane monotherapy (target level 14-20 mg/L) with glucocorticoid replacement; local therapies (ablation, radiotherapy) for oligometastases.
  2. 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.

Progressive after chemotherapy

  1. For my situation (progressive after chemotherapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab, cabozantinib, gemcitabine-capecitabine; control hormone excess; clinical trials.
  2. Am I a candidate for Pembrolizumab, Cabozantinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Cabozantinib, Pembrolizumab, Mitotane?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “No targeted therapy despite defined genomic subgroups”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Mitotane toxicity and narrow therapeutic window”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

37top

Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

13
Anti-angiogenic therapyAutologous stem cell transplant (high-dose therapy)Cardio-oncologyCytotoxic chemotherapyGermline (hereditary) testingImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Platinum agentsRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsThermal ablation (RFA, microwave, cryo)Topoisomerase-I inhibitors (and ADC payloads)

targets

6
KMT2A (MLL) rearrangementMETPD-1RETTP53VEGF / VEGFR

drugs

7
ApprovedSmall-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)
Cabozantinib · Cabometyx
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Not mapped hereAdrenolytic agent (DDD derivative)
Mitotane · Lysodren
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedSmall-molecule glucocorticoid receptor antagonist
Relacorilant · Lifyorli

companies

4
Corcept TherapeuticsExelixisIpsenMerck & Co. (MSD)

institutions

1
Rutgers Cancer Institute of New Jersey

pathways

2
p53 / RB / cell-cycle checkpointWnt / β-catenin

terms

4
Germline vs somatic mutationsHereditary cancer syndromesLi-Fraumeni syndrome (germline TP53)Rare cancers

Latest papers

top
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Adrenocortical carcinoma" OR ABSTRACT:"Adrenocortical carcinoma" OR TITLE:"ACC" OR ABSTRACT:"ACC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Adrenocortical carcinoma, not a curated reading list.

Connected

28top

Pages like this

not linked directly; found by shared links

technologies

8
Cytotoxic chemotherapyGermline (hereditary) testingImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Robotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsThermal ablation (RFA, microwave, cryo)

targets

3
PD-1TP53VEGF / VEGFR

drugs

7
ApprovedSmall-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)
Cabozantinib · Cabometyx
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Not mapped hereAdrenolytic agent (DDD derivative)
Mitotane · Lysodren
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedSmall-molecule glucocorticoid receptor antagonist
Relacorilant · Lifyorli

companies

3
Corcept TherapeuticsExelixisMerck & Co. (MSD)

institutions

1
Rutgers Cancer Institute of New Jersey

pathways

2
p53 / RB / cell-cycle checkpointWnt / β-catenin

terms

4
Germline vs somatic mutationsHereditary cancer syndromesLi-Fraumeni syndrome (germline TP53)Rare cancers