OnCo
Learn & contributeTeaching packs

Teaching pack: Adrenocortical carcinoma

Read the page

9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

Slide 1 of 9
  1. Teaching pack · Cancer · endocrine

    Adrenocortical carcinoma

    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.

    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice1 / 9
  2. What it is

    In two paragraphs

    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.

    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice2 / 9
  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    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.not mapped
    Advanced, aggressiveEDP-M (etoposide, doxorubicin, cisplatin + mitotane) ×6-8 with surgery for responders; streptozocin-mitotane second line.NCCN Category 2A
    Advanced, indolentMitotane monotherapy (target level 14-20 mg/L) with glucocorticoid replacement; local therapies (ablation, radiotherapy) for oligometastases.not mapped
    Progressive after chemotherapyPembrolizumab, cabozantinib, gemcitabine-capecitabine; control hormone excess; clinical trials.NCCN Category 2B
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice3 / 9
  4. State of the art

    Where the field stands

    • 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.
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice4 / 9
  5. History

    How we got here

    1. 1959Mitotane (o,p'-DDD) first used in ACC (Bergenstal)
    2. 1984Weiss histologic criteria
    3. 2007Adjuvant mitotane associated with longer recurrence-free survival (Terzolo, NEJM)
    4. 2009ENSAT staging
    5. 2012FIRM-ACT: EDP-M vs streptozocin-mitotane (NEJM)
    6. 2016TCGA/ENSAT genomic classification of ACC (Zheng, Cancer Cell)
    7. 2019Pembrolizumab phase 2 in ACC (Raj, JCO)
    8. 2023ADIUVO: no benefit of adjuvant mitotane in low-risk disease
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice5 / 9
  6. Pipeline

    What is coming

    • Cabozantinib (product)
    • Pembrolizumab (product)
    • Mitotane (product)
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice6 / 9
  7. Open problems

    What nobody has solved

    • 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.
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice7 / 9
  8. Quiz

    Check understanding

    1. What is the standard treatment for stage II-III triple-negative breast cancer today?
      Answer
      Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice8 / 9
  9. Sources

    Read the primary sources

    • ESE/ENSAT ACC guideline 2018: https://doi.org/10.1530/EJE-18-0608
    • FIRM-ACT (NEJM 2012): https://doi.org/10.1056/NEJMoa1200966
    • NCI PDQ: adrenocortical carcinoma: https://www.cancer.gov/types/adrenocortical/patient/adrenocortical-treatment-pdq
    • Wikipedia: https://en.wikipedia.org/wiki/Adrenocortical_carcinoma
    • Guideline: https://doi.org/10.1530/EJE-18-0608
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448
    Teaching pack: Adrenocortical carcinoma · OnCo, CC BY 4.0 · not medical advice9 / 9