The first 60 days: Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)
Advanced adrenocortical carcinoma is adrenal cortex cancer that has spread to distant organs or cannot be removed, one of the hardest endocrine cancers to treat. The standard is mitotane with etoposide, doxorubicin and cisplatin, established by the FIRM-ACT trial; limited spread is treated locally, hormone excess with steroid-blocking drugs, and immunotherapy helps a minority. Below, week by week, is what OnCo's record of Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- SurgeonNamed in the standard of care for: Low-burden, indolent disease.
- Medical oncologistNamed in the standard of care for: All patients, Low-burden, indolent disease, High-burden or progressive disease, first line, After EDP-M and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Low-burden, indolent disease.
- Transplant and cell therapy teamNamed in the standard of care for: High-burden or progressive disease, first line.
- Palliative and supportive care teamNamed in the standard of care for: High-burden or progressive disease, first line.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Mitotane from diagnosis with glucocorticoid replacement; adrenal enzyme inhibitors (metyrapone, osilodrostat, ketoconazole) for cortisol excess; thromboprophylaxis and infection vigilance.
Mitotane alone, with resection, thermal ablation or stereotactic radiotherapy of limited metastases.
- 3.High-burden or progressive disease, first lineESE/ENSAT guideline on adrenocortical carcinoma 2018
Etoposide, doxorubicin and cisplatin with mitotane (EDP-M, FIRM-ACT).
Gemcitabine with capecitabine; cabozantinib; pembrolizumab, especially for mismatch-repair-deficient tumours; streptozocin-mitotane; clinical trials.
Relacorilant with checkpoint inhibition for cortisol-secreting tumours; cabozantinib with immunotherapy; radiolabelled CYP11B tracers.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Ki-67 index and tumour burden, Hormone profile, above all cortisol, Plasma mitotane level, Mismatch repair status and tumour mutational burden, Germline TP53 and Lynch syndrome testing), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Synchronous metastatic adrenocortical carcinoma, Recurrent adrenocortical carcinoma after resection, Low-burden, slow-growing metastatic disease.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
All patients
- For my situation (all patients), which of the standard options do you recommend and why?Guideline options include: Mitotane from diagnosis with glucocorticoid replacement; adrenal enzyme inhibitors (metyrapone, osilodrostat, ketoconazole) for cortisol excess; thromboprophylaxis and infection vigilance.
- Am I a candidate for Mitotane, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Low-burden, indolent disease
- For my situation (low-burden, indolent disease), which of the standard options do you recommend and why?Guideline options include: Mitotane alone, with resection, thermal ablation or stereotactic radiotherapy of limited metastases.
- Am I a candidate for Mitotane, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
High-burden or progressive disease, first line
- For my situation (high-burden or progressive disease, first line), which of the standard options do you recommend and why?Guideline options include: Etoposide, doxorubicin and cisplatin with mitotane (EDP-M, FIRM-ACT).
- Am I a candidate for Etoposide, Doxorubicin, Cisplatin or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
After EDP-M
- For my situation (after edp-m), which of the standard options do you recommend and why?Guideline options include: Gemcitabine with capecitabine; cabozantinib; pembrolizumab, especially for mismatch-repair-deficient tumours; streptozocin-mitotane; clinical trials.
- Am I a candidate for Gemcitabine, Capecitabine, Cabozantinib or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Trials
- For my situation (trials), which of the standard options do you recommend and why?Guideline options include: Relacorilant with checkpoint inhibition for cortisol-secreting tumours; cabozantinib with immunotherapy; radiolabelled CYP11B tracers.
- Am I a candidate for Relacorilant, Cabozantinib, Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Cabozantinib, Pembrolizumab, Relacorilant, Mitotane?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?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?Supportive care improves quality of life and helps patients complete treatment.
- I read that “No second-line therapy has randomised evidence”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Most tumours are immunologically cold and cortisol excess worsens that”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable): the full pageAdvanced adrenocortical carcinoma is adrenal cortex cancer that has spread to distant organs or cannot be removed, one of the hardest endocrine cancers to treat. The standard is mitotane with etoposide, doxorubicin and cisplatin, established by the FIRM-ACT trial; limited spread is treated locally, hormone excess with steroid-blocking drugs, and immunotherapy helps a minority.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Adrenalectomy: Removing an adrenal gland.
- Germline vs somatic mutations: Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.
- Tumour mutational burden (TMB): How many mutations a tumour has.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
Every term links to the glossary.