Medical Oncology · Adrenocortical Carcinoma

Treating Advanced or Recurrent Disease

At a Glance

For advanced or recurrent adrenocortical carcinoma, treatment is individualized. Fit patients needing tumor shrinkage may receive EDP-M, while surgery, radiation, ablation, mitotane, immunotherapy, or clinical trials may be considered based on tumor spread and test results.

When Adrenocortical Carcinoma (ACC) is advanced, metastatic (spread to other organs), or has returned after surgery, the treatment approach becomes more complex. Your care team will focus on controlling the tumor’s growth while managing symptoms and protecting your quality of life ^[1]^[2]. Treatment choice depends on the tumor pace, your prior therapy, fitness level, and molecular findings.

Systemic Therapy: The EDP-M Regimen

A well-established standard for aggressive or high-volume advanced ACC is a combination of three chemotherapy drugs plus mitotane, known as EDP-M ^[3]^[4].

Etoposide
Doxorubicin
Platinum (Cisplatin)
Mitotane

In the FIRM-ACT clinical trial, patients on EDP-M showed higher response rates and a longer time before the cancer started growing again compared to other treatments, though it did not conclusively prove a massive overall survival improvement ^[3]^[5]. Because EDP-M is an intensive regimen, it is usually selected for patients who are fit enough to tolerate it and who need the tumor to shrink ^[1]^[6].

Protecting Your Health During EDP-M

EDP-M is a “hard-hitting” treatment, and about 41% of patients experience significant side effects ^[7]. Proactive supportive care is a critical part of your treatment plan:

Preventing Infection: EDP-M can severely drop your white blood cell count (neutropenia). Depending on your individual protocol and risk, your team may prescribe G-CSF (a growth factor injection) to boost your immune system ^[8]. You must know what temperature requires an immediate emergency call.
Kidney Protection: Cisplatin can be hard on the kidneys, ears, and nerves. You will receive intensive IV hydration, and doctors may use a 24-hour continuous infusion to make it easier on your body ^[8].
Hormone Control: If your tumor produces cortisol, the excess must be assessed and treated urgently, often in parallel with cancer therapy using specific endocrine-directed medications ^[8]^[9].
Monitoring Adrenal Function: If you feel extreme fatigue, nausea, or weakness between cycles, don’t assume it’s just the chemo. It could be adrenal insufficiency caused by the mitotane, requiring your doctor to adjust your steroid replacement ^[8]^[3].

Exploring All Avenues: Trials and Targeted Therapy

EDP-M is not the only pathway. Depending on your situation, alternatives include:

Mitotane Alone: For selected indolent (slower-growing) or low-volume disease, mitotane monotherapy may be appropriate.
Molecular Testing and Immunotherapy: Tumors should undergo biomarker testing. Depending on the results, checkpoint inhibitors (immunotherapy) or tissue-agnostic treatments may be an option.
Clinical Trials: Accessing clinical trials is a crucial pathway for discovering new, effective options for rare cancers.

The Role of Repeat Surgery and Locoregional Therapies

If the cancer returns, you may not necessarily need to start systemic chemotherapy immediately. Repeat surgery or metastasectomy (removing individual spread sites) can be discussed in an expert tumor board if favorable factors exist ^[1]^[10]:

The cancer returned more than 12 months after your first surgery.
The recurrence involves only one or a few spots (oligometastatic disease).
The surgeon believes they can remove every visible sign of the cancer ^[11]^[12].

While patients selected for repeat surgery often have better outcomes, this is largely influenced by the selection of patients with more favorable, slower-growing disease ^[13]^[11].

When surgery isn’t the right choice, doctors can use targeted “locoregional” treatments to destroy specific tumors:

Radiation (SBRT/RT): High-dose radiation can be very effective at controlling individual lesions, especially in the lungs or bones ^[14]^[15].
Thermal Ablation: Doctors use heat (radiofrequency/microwave) or cold (cryoablation) to treat small, individual metastases ^[16]^[17].
Embolization: For tumors in the liver, doctors can block the blood supply to the tumor or deliver chemotherapy directly into the liver (TACE) ^[16]^[18].

Common questions in this guide

What does EDP-M mean, and who may receive it?

EDP-M combines etoposide, doxorubicin, cisplatin, a platinum drug, and mitotane. It is a well-established option for aggressive or high-volume advanced adrenocortical carcinoma, especially when a person is fit enough for intensive treatment and tumor shrinkage is needed.

How will doctors reduce the risks of EDP-M chemotherapy?

The team may use a white-cell growth factor called G-CSF to lower infection risk, depending on your treatment plan and risk. Cisplatin is supported with intensive IV hydration and monitoring for kidney, hearing, and nerve problems. Ask your team which temperature or symptoms require an emergency call.

What symptoms could signal adrenal insufficiency during mitotane treatment?

Extreme fatigue, nausea, or weakness between treatment cycles may be signs of adrenal insufficiency rather than ordinary chemotherapy fatigue. Contact your treatment team promptly because mitotane can reduce adrenal function and your steroid replacement may need adjustment.

Could immunotherapy or a clinical trial be an option for advanced ACC?

Biomarker testing can help show whether checkpoint immunotherapy or a treatment that works across different tumor types may be appropriate. Clinical trials are also an important option for this rare cancer, and eligibility depends on prior treatment, overall health, and tumor findings.

When can recurrent ACC be treated with repeat surgery?

An expert tumor board may consider repeat surgery or removal of individual spread sites when the cancer returns after more than 12 months, is limited to one or a few spots, and the surgeon believes all visible disease can be removed. People selected for surgery often have better outcomes, but that may partly reflect their slower-growing, more favorable disease.

What treatments can target individual metastatic tumors if surgery is not possible?

High-dose radiation, including SBRT, can control selected tumors, particularly in the lungs or bones. Heat- or cold-based ablation can treat small spread sites, and liver embolization or TACE can block blood flow or deliver chemotherapy to tumors in the liver.

Is mitotane alone ever used for advanced ACC?

Mitotane alone may be appropriate for selected people with slower-growing or low-volume disease. The choice depends on tumor behavior, prior treatment, overall health, and the goals of care.

Get notified when new evidence is published on adrenal carcinoma.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

Key takeaways

EDP-M combines etoposide, doxorubicin, cisplatin, and mitotane and is often used for aggressive or high-volume advanced ACC in people able to tolerate intensive treatment.
Supportive care may include infection prevention, G-CSF when appropriate, IV hydration, and monitoring for kidney, nerve, hearing, and adrenal effects.
Molecular testing may identify options such as checkpoint immunotherapy or treatments that work across tumor types, and clinical trials should be considered.
Selected recurrences may be treated with repeat surgery or metastasectomy when disease is limited, returns after more than 12 months, and all visible disease can be removed.
SBRT or other radiation, thermal ablation, and liver embolization can control individual metastatic lesions when surgery is not suitable.

References (18)

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This page explains treatment options and supportive care for advanced or recurrent adrenocortical carcinoma for informational purposes only and does not constitute medical advice. Your oncology team should tailor treatment and emergency instructions to your health and care plan.

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