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What is adrenocortical carcinoma?
Adrenocortical carcinoma (ACC) is a rare cancer that begins in the cortex — the outer, hormone-producing layer — of an adrenal gland, the small gland that sits on top of each kidney. Many of these tumors are 'functioning,' meaning they make excess hormones such as cortisol or androgens; this can cause weight gain, high blood pressure, easy bruising, diabetes, or hormonal changes that often bring the tumor to attention. Others are found because they grow large enough to cause pain or are spotted incidentally on a scan. ACC is aggressive and tends to recur, so treatment is intensive and coordinated by an expert center. The single most important factor is whether the tumor can be removed completely by an experienced surgeon. After surgery, an adrenal-specific medicine called mitotane is commonly used to lower the chance of recurrence, and radiation to the tumor bed can further reduce local relapse in higher-risk cases.
The main types
Doctors group adrenocortical carcinoma by where it starts and how it behaves:
| Type | What it means, simply |
|---|---|
| Functioning (hormone-producing) | Makes excess hormones — most often cortisol (causing Cushing-like changes) or androgens — which cause symptoms that often lead to diagnosis. |
| Non-functioning | Does not produce noticeable excess hormones; usually found because of its size, local symptoms, or incidentally on imaging. |
| Oncocytic and other histologic variants | Less common microscopic subtypes that pathologists distinguish because they can behave differently and affect treatment decisions. |
Staging, in plain terms
ACC is staged with the ENSAT system, a TNM-based scheme that considers the size and local extent of the tumor (T), spread to lymph nodes (N), and spread to distant organs (M). Stage and whether the tumor is completely removed are the strongest predictors of outcome.
| ENSAT / TNM staging for adrenocortical carcinoma | What it generally means |
|---|---|
| Stage I | A smaller tumor (5 cm or less) confined to the adrenal gland. Best outlook, especially when fully removed. |
| Stage II | A larger tumor (over 5 cm) still confined to the adrenal gland. |
| Stage III | Tumor that invades nearby tissue or has reached regional lymph nodes or nearby veins. |
| Stage IV | Tumor that has spread to distant organs such as the liver, lungs, or bone. |
The standard of care
Adrenocortical Carcinoma is almost always treated by a team that may include a surgeon, a medical oncologist, and a radiation oncologist, combining therapies for the best result. The usual building blocks are:
Complete surgical removal
Removing the entire tumor with clear margins, ideally by a high-volume adrenal surgeon, gives the best chance of cure and is the foundation of treatment.
Mitotane (adrenal-specific medicine)
An oral drug that targets adrenal cortex cells; it is commonly given after surgery to reduce recurrence and is also used for advanced disease, with careful monitoring of blood levels and hormone replacement.
Chemotherapy for advanced disease
For cancer that cannot be removed or has spread, the EDP-M regimen (etoposide, doxorubicin, cisplatin, plus mitotane) is the established standard, based on the FIRM-ACT trial.
Hormone control and supportive care
Medicines to control hormone excess (such as cortisol-lowering drugs) and to replace needed hormones are an important part of care and symptom relief.
How radiation treatment works
Radiation damages the DNA inside cancer cells so they can no longer divide and survive, while normal cells repair themselves more effectively. In adrenocortical carcinoma, surgery and mitotane lead treatment, and radiation plays a focused supporting role: targeting the tumor bed after surgery to lower the chance of local return, and precisely controlling isolated areas of spread. Modern techniques shape the beam to the target and spare nearby organs such as the kidney, liver, and bowel. Radiation is delivered as short, painless daily sessions and leaves no radioactivity in your body.
The main ways radiation is delivered for adrenocortical carcinoma:
Radiation to the tumor bed (adjuvant)
After surgery, targeted radiation to where the tumor was can reduce the chance of local recurrence, especially for large tumors, close or positive margins, or when the tumor was disrupted during removal.
Stereotactic body radiation (SBRT)
Precise, high-dose radiation can control isolated areas of spread — for example to bone, lung, or liver — when the goal is durable control of a limited number of sites.
Palliative radiation
Short courses of radiation effectively relieve pain from bone metastases and other symptoms in advanced disease.
Latest studies shaping care
Care keeps improving — often toward getting the same excellent results with less burden on patients. A few developments:
EDP-M as the chemotherapy standard: The landmark FIRM-ACT trial established etoposide, doxorubicin, and cisplatin plus mitotane (EDP-M) as the first-line chemotherapy for advanced adrenocortical carcinoma, and it remains the reference regimen.[1]
FIRM-ACT trial and subsequent ACC guidelines (2012–2025)
Refining who needs mitotane after surgery: Ongoing research, including the ADIUVO line of studies, is clarifying which patients benefit most from adjuvant mitotane, aiming to spare low-risk patients its side effects while treating higher-risk patients.[2]
Adjuvant ACC therapy studies (2020–2025)
Role of adjuvant radiation to the tumor bed: Series support tumor-bed radiation after surgery to reduce local recurrence in higher-risk cases, and stereotactic radiation is increasingly used to control limited metastatic disease.[3]
Radiation oncology ACC outcome series (2021–2025)
Common questions
Why is surgery by a specialist so important? Adrenocortical carcinoma is best controlled when the entire tumor is removed in one piece with clear margins. Experienced, high-volume adrenal surgeons are more likely to achieve a complete removal without rupturing the tumor, which strongly improves the chance of cure.
What is mitotane and why might I take it? Mitotane is a medicine that specifically acts on adrenal cortex cells. It is often given after surgery to lower the risk of the cancer coming back, and it is used for advanced disease. Because it affects hormone production, your team will monitor blood levels and provide hormone replacement as needed.
Does this cancer cause hormone symptoms? Often yes. Many adrenocortical carcinomas make excess hormones, which can cause weight gain, high blood pressure, high blood sugar, easy bruising, or other hormonal changes. Controlling these hormones is an important part of treatment and comfort.
References
Numbered sources for the studies cited above. Links open the primary publication on PubMed or the publisher’s site.