General Information About Adrenocortical Carcinoma
Adrenocortical carcinoma is a rare disease in which malignant (cancer) cells form in
the outer layer of the adrenal gland.
There are two adrenal glands. The adrenal glands are small and shaped like a triangle. One adrenal gland sits on top of each kidney. Each adrenal gland has two parts. The outer layer of the adrenal gland is the adrenal cortex. The center of the adrenal gland is the adrenal medulla.
The adrenal cortex makes important hormones that:
- Balance the water and salt in the body.
- Help keep blood pressure normal.
- Help manage the body's use of protein, fat, and carbohydrates.
- Cause the body to have masculine or feminine characteristics.
The adrenal medulla makes hormones that help the body react to stress.
Adrenocortical carcinoma is also called cancer of the adrenal cortex. A tumor of the adrenal cortex may be functioning (makes more hormones than normal) or nonfunctioning (does not make hormones). The hormones made by functioning tumors may cause certain signs or symptoms of disease.
Cancer that forms in the adrenal medulla is called pheochromocytoma.
Having certain genetic conditions increases the risk of developing adrenocortical carcinoma.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for adrenocortical carcinoma include having the following hereditary diseases:
- Li-Fraumeni syndrome.
- Beckwith-Wiedemann syndrome.
- Carney complex.
Possible signs of adrenocortical carcinoma include pain in the abdomen and certain physical changes.
These and other symptoms may be caused by adrenocortical carcinoma:
- A lump in the abdomen.
- Pain the abdomen or back.
A nonfunctioning adrenocortical tumor may not cause symptoms in the early stages.
A functioning adrenocortical tumor makes too much of a certain hormone (cortisol, aldosterone, testosterone, or estrogen).
Too much cortisol may cause:
- Weight gain in the face, neck, and trunk of the body and thin arms and legs.
- Growth of fine hair on the face, upper back, or arms.
- A round, red, full face.
- A lump of fat on the back of the neck.
- A deepening of the voice and swelling of the sex organs or breasts in both males and females.
- Muscle weakness.
- High blood sugar.
- High blood pressure.
Too much aldosterone may cause:
- High blood pressure.
- Muscle weakness or cramps.
- Frequent urination.
- Feeling thirsty.
Too much testosterone (in women) may cause:
- Growth of fine hair on the face, upper back, or arms.
- Acne.
- Balding.
- A deepening of the voice.
- No menstrual periods.
Men who make too much testosterone do not usually have symptoms.
Too much estrogen (in women) may cause:
- Irregular menstrual periods in women who have not gone through menopause.
- Menstrual bleeding in women who have gone through menopause.
Too much estrogen (in men) may cause:
- Growth of breast tissue.
- Lower sex drive.
- Impotence.
These and other symptoms may be caused by adrenocortical carcinoma. Other conditions may cause the same symptoms. A doctor should be consulted if any of these problems occur.
Imaging studies and tests that examine the blood and urine are used to detect (find) and diagnose adrenocortical carcinoma.
The tests and procedures used to diagnose adrenocortical carcinoma depend on the patient's symptoms. The following tests and procedures may be used:
- Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
- Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of cortisol or 17-ketosteroids. A higher than normal amount of these in the urine may be a sign of disease in the adrenal cortex.
- Low-dosedexamethasone suppression test: A test in which one or more small doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
- High-dose dexamethasone suppression test: A test in which one or more high doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
- Blood chemistry study: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as potassium or sodium, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
- Blood tests: Tests to measure the levels of testosterone or estrogen in the blood. A higher than normal amount of these hormones that may be a sign of adrenocortical carcinoma.
- CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
- MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). An MRI of the abdomen is done to diagnose adrenocortical carcinoma.
- Adrenal angiography: A procedure to look at the arteries and the flow of blood near the adrenal gland. A contrast dye is injected into the adrenal arteries. As the dye moves through the blood vessel, a series of x-rays are taken to see if any arteries are blocked.
- Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal gland. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the vein, a series of x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormal hormone levels.
- PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
Certain factors affect the prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) and treatment options depend on the following:
- The stage of the cancer (the size of the tumor and whether it is in the adrenal gland only or has spread to other places in the body).
- Whether the tumor can be completely removed in surgery.
- Whether the cancer has been treated in the past.
- The patient's general health.
Adrenocortical carcinoma may be cured if treated at an early stage.
Top
Stages of Adrenocortical Carcinoma
After adrenocortical carcinoma has been diagnosed, tests are done to find out if cancer cells have spread within the adrenal gland or to other parts of the body.
The process used to find out if cancer has spread within the adrenal gland or to other
parts of the body is called staging. The information gathered from the
staging process determines the stage of the disease. It is important to know
the stage in order to plan treatment. The following tests and
procedures may be used in the staging process:
- CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen or chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
- MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium may be injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
- Adrenalangiography: A procedure to look at the arteries and the flow of blood near the adrenal gland. A contrast dye is injected into the adrenal arteries. As the dye moves through the blood vessel, a series of x-rays are taken to see if any arteries are blocked.
- Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal gland. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the vein, x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormalhormone levels.
- Cavagram: A procedure to look at the inferior vena cava and the flow of blood through the inferior vena cava. A contrast dye is injected into a blood vessel. As the contrast dye moves through the blood vessel to the inferior vena cava, a series of x-rays are taken to see if there are any changes to the inferior vena cava and the flow of blood through the inferior vena cava.
- Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs, such as the vena cava, and make echoes. The echoes form a picture of body tissues called a sonogram.
- Adrenalectomy: A procedure to remove the entire adrenal gland. A tissue sample is viewed under a microscope by a pathologist to check for signs of cancer.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
The following stages are used for adrenocortical carcinoma:
|
| Pea, peanut, walnut, and lime show tumor sizes. |
Stage I
In stage I, the tumor is 5 centimeters or smaller and is found only in the adrenal gland.
Stage II
In stage II, the tumor is larger than 5 centimeters and is found only in the adrenal gland.
Stage III
In stage III, the tumor can be any size and may have spread to fat or lymph nodes near the adrenal gland.
Stage IV
In stage IV, the tumor can be any size and has spread:
- to fat or organs and to lymph nodes near the adrenal gland; or
- to other parts of the body. Adrenocortical carcinoma commonly spreads to the lung, liver, bones, and peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen).
Top
Recurrent Adrenocortical Carcinoma
Recurrentadrenocortical carcinoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the adrenal cortex or in other parts of the body.
Top
Treatment Option Overview
There are different types of treatment for patients with adrenocortical carcinoma.
Different types of treatments are available for patients with adrenocortical carcinoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Three types of standard treatment are used:
Surgery
Surgery to remove the adrenal gland (adrenalectomy) is often used to treat adrenocortical carcinoma. Sometimes the nearby lymph nodes are also removed.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Mitotane may be used to treat adrenocortical carcinoma. Mitotane stops the adrenal cortex from making hormones and relieves symptoms caused by the hormones.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
Biologic therapy
Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Top
Treatment Options by Stage
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Stage I Adrenocortical Carcinoma
Treatment of stage I adrenocortical carcinoma is usually surgery (adrenalectomy). Lymph nodes may be removed if they are larger than normal.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Stage II Adrenocortical Carcinoma
Treatment of stage II adrenocortical carcinoma is usually surgery (adrenalectomy). Lymph nodes may be removed if they are larger than normal.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Stage III Adrenocortical Carcinoma
Treatment of stage III adrenocortical carcinoma may include the following:
- Surgery (adrenalectomy with or without removal of lymph nodes).
- A clinical trial of radiation therapy for tumors that cannot be removed by surgery.
- A clinical trial of mitotane for tumors that cannot be completely removed by surgery.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Stage IV Adrenocortical Carcinoma
Treatment of stage IV adrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:
- Mitotane therapy.
- Radiation therapy to bones where cancer has spread.
- Chemotherapy followed by surgery to remove the tumor.
- Surgery to remove the tumor.
- Surgery to remove cancer from places where it has spread.
- A clinical trial of chemotherapy or biologic therapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Top
Treatment Options for Recurrent Adrenocortical Carcinoma
Treatment of recurrentadrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:
- Surgery to remove the tumor.
- Surgery to remove the cancer from places where it has spread.
- A clinical trial of chemotherapy or biologic therapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent adrenocortical carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Top
To Learn More About Adrenocortical Carcinoma
For more information from the National Cancer Institute about adrenocortical carcinoma, see the Adrenocortical Carcinoma Home Page.
For general cancer information and other resources from the National Cancer Institute, see the following:
Top
This information is provided by the National Cancer Institute.
This information was last updated on October 14, 2009.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adrenocortical carcinoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Top
General Information
Adrenocortical carcinoma is a rare tumor that affects only 1 to 2 persons per
one million population. It usually occurs in adults, and the median age at
diagnosis is 44 years. Although adrenal carcinoma is potentially curable at early stages, only 30%
of these malignancies are confined to the adrenal gland at the time of
diagnosis.[1]
Radical
surgical excision is the treatment of choice for patients with localized malignancies and
remains the only method by which long-term disease-free survival may be
achieved. Overall 5-year survival for tumors resected for cure is
approximately 40%.
Retrospective studies have identified two important
prognostic factors: completeness of resection and stage of disease. Patients
without evidence of invasion into local tissues or spread to lymph nodes have
an improved prognosis.[2] The role of DNA ploidy as a prognostic indicator is
controversial, with some [3] studies, such as ECOG-1879, for example, showing correlation between aneuploidy and
prognosis, and other studies [2][4] showing no correlation.
Approximately 60% of patients present with symptoms related to excessive
hormone secretion, but hormone testing reveals that 60% to 80% of tumors are
functioning.[5][6] Nonfunctioning carcinomas may be heralded by symptoms of
local invasion by tumor or by metastases. Initial evaluation should include,
in addition to appropriate endocrine studies, computed tomography and/or
magnetic resonance imaging of the abdomen. Selective angiography and adrenal
venography may be helpful in identifying smaller lesions and for distinguishing tumors of
the adrenal gland from tumors of the upper pole of the kidney. Although the use of positron emission tomography may be effective in identifying unsuspected sites of metastases, its role as a staging tool is unclear.[7] The detection
of metastatic lesions may allow effective palliation of both functioning and
nonfunctioning lesions.
The most common sites of metastases are the peritoneum, lung, liver, and bone.
Palliation of metastatic functioning tumors may be achieved by resection of
both the primary tumor and metastatic lesions. Unresectable or widely
disseminated tumors may be palliated by antihormonal therapy with mitotane,
systemic chemotherapy, or (for localized lesions) radiation therapy. However,
survival for patients with stage IV tumors is usually less than 9 months unless
a complete remission is achieved.[6][8][9][10] There is no convincing
evidence to date that systemic therapy will improve the survival duration of patients
with adrenal cancer.
References:
Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39.
Lee JE, Berger DH, el-Naggar AK, et al.: Surgical management, DNA content, and patient survival in adrenal cortical carcinoma. Surgery 118 (6): 1090-8, 1995.
Camuto P, Schinella R, Gilchrist K, et al.: Adrenal cortical carcinoma: flow cytometric study of 22 cases, an ECOG study. Urology 37 (4): 380-4, 1991.
Haak HR, Cornelisse CJ, Hermans J, et al.: Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma. Br J Cancer 68 (1): 151-5, 1993.
Icard P, Chapuis Y, Andreassian B, et al.: Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. Surgery 112 (6): 972-9; discussion 979-80, 1992.
Luton JP, Cerdas S, Billaud L, et al.: Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 322 (17): 1195-201, 1990.
Becherer A, Vierhapper H, Pötzi C, et al.: FDG-PET in adrenocortical carcinoma. Cancer Biother Radiopharm 16 (4): 289-95, 2001.
Brennan MF: Adrenocortical carcinoma. CA Cancer J Clin 37 (6): 348-65, 1987 Nov-Dec.
Cohn K, Gottesman L, Brennan M: Adrenocortical carcinoma. Surgery 100 (6): 1170-7, 1986.
Wooten MD, King DK: Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72 (11): 3145-55, 1993.
Top
Cellular Classification
Adrenocortical carcinoma can be classified as follows:
- Differentiated: Functioning tumors are usually differentiated.
- Anaplastic: Production of hormones by anaplastic tumors is rare.
- Hormonal: Approximately 60% of adrenocortical carcinomas produce hormones.
The associated clinical syndromes include the following:[1][2][3]
- Hypercortisolism (Cushing syndrome).
- Adrenogenital syndrome.
- Virilization.
- Feminization.
- Precocious puberty.
- Hyperaldosteronism.
- Primary hyperaldosteronism (Conn syndrome).
References:
Javadpour N, Woltering EA, Brennan MF: Adrenal neoplasms. Curr Probl Surg 17 (1): 1-52, 1980.
Nader S, Hickey RC, Sellin RV, et al.: Adrenal cortical carcinoma. A study of 77 cases. Cancer 52 (4): 707-11, 1983.
Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39.
Top
Stage Information
The stage of adrenocortical carcinoma is determined by the size of the primary
tumor, the degree of local invasion, and whether it has spread to regional
lymph nodes or distant sites.[1][2][3][4] Proper staging should include computed
tomography (CT) of the abdomen. Magnetic resonance imaging (MRI) may add
specificity to CT evaluation of an adrenal mass.[5] In-phase and out-of-phase
T1-weighted imaging may be the most effective noninvasive method to
differentiate benign from malignant adrenal masses. MRI can also often clearly
demonstrate any evidence of extracapsular tumor invasion, extension into the
vena cava, or metastases. Patency of surrounding vessels can often be
demonstrated with gadolinium-enhanced sequences or flip-angle techniques.[6]
Vena caval contrast studies and angiography may provide additional staging
information and allow for a more complete preoperative assessment. A review of
published data from 608 patients revealed the following stage distribution at
diagnosis: 3% stage I, 29% stage II, 20% stage III, and 49% stage IV.[7]
Stages are defined by TNM classification.[8]
TNM Definitions
Tumor (T)
- T1: Tumor 5 cm or less in size; invasion
absent
- T2: Tumor greater than 5 cm in size; invasion
absent
- T3: Tumor outside adrenal in fat
- T4: Tumor invading adjacent organs
Lymph nodes (N)
- N0: No positive lymph nodes
- N1: Positive lymph nodes
Metastases (M)
- M0: No distant metastases
- M1: Distant metastases
Stage I
Stage II
Stage III
- T1, N1, M0
- T2, N1, M0
- T3, N0, M0
Stage IV
- T3, N1, M0
- T4, N1, M0
- Any T, any N, M1
References:
Cerfolio RJ, Vaughan ED Jr, Brennan TG Jr, et al.: Accuracy of computed tomography in predicting adrenal tumor size. Surg Gynecol Obstet 176 (4): 307-9, 1993.
Brennan MF: Adrenocortical carcinoma. CA Cancer J Clin 37 (6): 348-65, 1987 Nov-Dec.
Cohn K, Gottesman L, Brennan M: Adrenocortical carcinoma. Surgery 100 (6): 1170-7, 1986.
Nader S, Hickey RC, Sellin RV, et al.: Adrenal cortical carcinoma. A study of 77 cases. Cancer 52 (4): 707-11, 1983.
Doppman JL, Reinig JW, Dwyer AJ, et al.: Differentiation of adrenal masses by magnetic resonance imaging. Surgery 102 (6): 1018-26, 1987.
Brown ED, Semelka RC: Magnetic resonance imaging of the adrenal gland and kidney. Top Magn Reson Imaging 7 (2): 90-101, 1995 Spring.
Wooten MD, King DK: Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72 (11): 3145-55, 1993.
Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39.
Top
Stage I Adrenocortical Carcinoma
Standard treatment options:
- Complete surgical removal of the tumor is the treatment of choice for patients
with stage I adrenocortical carcinomas. The long-term survival of patients with
nonfunctioning tumors is comparable to that of patients with functioning tumors. The removal
of regional lymph nodes that are not clinically enlarged is not indicated.[1][2][3][4][5]
Treatment options under clinical evaluation:
- Adjuvant radiation or chemotherapy with mitotane has not been proven to be of
value in improving survival.[5][6]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage I adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Javadpour N, Woltering EA, Brennan MF: Adrenal neoplasms. Curr Probl Surg 17 (1): 1-52, 1980.
Brennan MF: Adrenocortical carcinoma. CA Cancer J Clin 37 (6): 348-65, 1987 Nov-Dec.
Cohn K, Gottesman L, Brennan M: Adrenocortical carcinoma. Surgery 100 (6): 1170-7, 1986.
Icard P, Chapuis Y, Andreassian B, et al.: Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. Surgery 112 (6): 972-9; discussion 979-80, 1992.
Luton JP, Cerdas S, Billaud L, et al.: Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 322 (17): 1195-201, 1990.
Vassilopoulou-Sellin R, Guinee VF, Klein MJ, et al.: Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. Cancer 71 (10): 3119-23, 1993.
Top
Stage II Adrenocortical Carcinoma
Standard treatment options:
- Complete surgical removal of the tumor is the treatment of choice for patients
with stage II adrenocortical carcinomas. The long-term survival of patients with
nonfunctioning tumors is comparable to that of patients with functioning tumors. The removal
of regional lymph nodes that are not clinically enlarged is not indicated.[1][2][3][4][5]
Treatment options under clinical evaluation:
- Adjuvant radiation or chemotherapy with mitotane has not been proven to be of
value in improving survival.[5][6]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage II adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Javadpour N, Woltering EA, Brennan MF: Adrenal neoplasms. Curr Probl Surg 17 (1): 1-52, 1980.
Brennan MF: Adrenocortical carcinoma. CA Cancer J Clin 37 (6): 348-65, 1987 Nov-Dec.
Cohn K, Gottesman L, Brennan M: Adrenocortical carcinoma. Surgery 100 (6): 1170-7, 1986.
Icard P, Chapuis Y, Andreassian B, et al.: Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. Surgery 112 (6): 972-9; discussion 979-80, 1992.
Luton JP, Cerdas S, Billaud L, et al.: Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 322 (17): 1195-201, 1990.
Vassilopoulou-Sellin R, Guinee VF, Klein MJ, et al.: Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. Cancer 71 (10): 3119-23, 1993.
Top
Stage III Adrenocortical Carcinoma
Standard treatment options:
- Complete surgical removal of the tumor, with or without regional lymph node
dissection is the treatment of choice for patients with stage III adrenocortical carcinomas. The treatment of patients who have tumors with local invasion, but
without clinically enlarged regional lymph nodes, is complete surgical removal
as for stage I and stage II tumors. For those with enlarged regional lymph
nodes, a lymph node dissection should be included in the procedure. These
patients are at a high risk for disease recurrence and should be considered for
enrollment in a clinical trial.
Treatment options under clinical evaluation:
- Clinical trials are appropriate for newly diagnosed patients when possible.
- Radiation therapy: 4,200 rads to 5,000 rads given for a period of 4 weeks to
patients with localized but unresectable tumors.[1]
- For patients unable to undergo complete resection, mitotane in doses as high as
10 to 12 grams per day can be considered. This antitumor drug produces useful
clinical responses that average 10 months in duration in about 30% of patients
with measurable metastases. Responses in patients who achieve complete
remission can be durable. Approximately 80% of treated patients with
functioning tumors will show substantial diminution in hormone production. The
drug is not usually used unless either radiologically evaluable metastases are
present or the residual tumor is producing measurable levels of hormone.[2][3]
Currently, no apparent role exists for mitotane as adjuvant therapy if the
patient has undergone complete resection of the tumor.[3][4]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage III adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Percarpio B, Knowlton AH: Radiation therapy of adrenal cortical carcinoma. Acta Radiol Ther Phys Biol 15 (4): 288-92, 1976.
Lubitz JA, Freeman L, Okun R: Mitotane use in inoperable adrenal cortical carcinoma. JAMA 223 (10): 1109-12, 1973.
Luton JP, Cerdas S, Billaud L, et al.: Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 322 (17): 1195-201, 1990.
Vassilopoulou-Sellin R, Guinee VF, Klein MJ, et al.: Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. Cancer 71 (10): 3119-23, 1993.
Top
Stage IV Adrenocortical Carcinoma
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Temporary palliation of disseminated adrenocortical carcinomas can sometimes be
achieved with the chemotherapeutic agent mitotane. Although measurable partial
remissions are unusual and are reported in only 19% to 34% of cases, excellent
palliation of hormone symptoms is commonly observed.[1] Prolonged treatment
with mitotane, however, is often limited by gastrointestinal and neurologic
toxicity. Local recurrences and selected sites of metastatic disease can
sometimes be palliated surgically.[2]
Clinical trials such as ECOG-1879 and SWOG-8325 are appropriate and should be considered whenever possible,
especially phase I and II trials that evaluate newer chemotherapeutic and
biologic agents.[3][4][5][6] Palliative chemotherapy with cisplatin-based regimens
has produced objective responses in approximately 30% of patients
treated.[4][5][7][8] One study reported that doxorubicin produced objective
responses in 3 of 16 patients with poorly differentiated, nonhormone-producing
tumors but no responses in 15 patients whose disease did not respond to
mitotane.[3]
Use of both platinum-based chemotherapy and mitotane achieved a 48.6% objective response and median time-to-progression of 18 months in responders.[9][Level of evidence: 3iiDiv] In 10 of 72 patients, subsequent surgical resection was possible.
Standard treatment options:
- Chemotherapy with mitotane.[1]
- Radiation therapy to bone metastases.[10]
-
Surgical removal of localized metastases, particularly those that are
functioning.[2]
Treatment options under clinical evaluation:
- Cisplatin has been reported to produce beneficial effects in some selected
patients with metastatic disease.[7][8][11]
- Clinical trials of other chemotherapy regimens.[3][4][5][6]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage IV adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Lubitz JA, Freeman L, Okun R: Mitotane use in inoperable adrenal cortical carcinoma. JAMA 223 (10): 1109-12, 1973.
Pommier RF, Brennan MF: An eleven-year experience with adrenocortical carcinoma. Surgery 112 (6): 963-70; discussion 970-1, 1992.
Decker RA, Elson P, Hogan TF, et al.: Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma. Surgery 110 (6): 1006-13, 1991.
Bukowski RM, Wolfe M, Levine HS, et al.: Phase II trial of mitotane and cisplatin in patients with adrenal carcinoma: a Southwest Oncology Group study. J Clin Oncol 11 (1): 161-5, 1993.
Hesketh PJ, McCaffrey RP, Finkel HE, et al.: Cisplatin-based treatment of adrenocortical carcinoma. Cancer Treat Rep 71 (2): 222-4, 1987.
Schlumberger M, Ostronoff M, Bellaiche M, et al.: 5-Fluorouracil, doxorubicin, and cisplatin regimen in adrenal cortical carcinoma. Cancer 61 (8): 1492-4, 1988.
Tattersall MH, Lander H, Bain B, et al.: Cis-platinum treatment of metastatic adrenal carcinoma. Med J Aust 1 (9): 419-21, 1980.
Chun HG, Yagoda A, Kemeny N, et al.: Cisplatin for adrenal cortical carcinoma. Cancer Treat Rep 67 (5): 513-4, 1983.
Berruti A, Terzolo M, Sperone P, et al.: Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer 12 (3): 657-66, 2005.
Percarpio B, Knowlton AH: Radiation therapy of adrenal cortical carcinoma. Acta Radiol Ther Phys Biol 15 (4): 288-92, 1976.
Haq MM, Legha SS, Samaan NA, et al.: Cytotoxic chemotherapy in adrenal cortical carcinoma. Cancer Treat Rep 64 (8-9): 909-13, 1980 Aug-Sep.
Top
Recurrent Adrenocortical Carcinoma
The question and selection of further treatment for patients with adrenocortical carcinoma
depends on many factors, including previous treatment and site of recurrence as
well as individual patient considerations. Local recurrence and selected sites
of metastatic disease can sometimes be palliated by surgery. Although none of
these patients can be considered curable, palliation of hormonal symptoms and
occasional 5-year survivals can be achieved.[1][2] Substantial morbidity,
however, is associated with resection of these recurrent tumors.[2] Clinical
trials, such as ECOG-1879 and SWOG-8325, are appropriate and should be considered whenever possible, especially
phase I and II trials that evaluate newer chemotherapeutic and biological
agents.[3][4][5][6][7]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
recurrent adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Pommier RF, Brennan MF: An eleven-year experience with adrenocortical carcinoma. Surgery 112 (6): 963-70; discussion 970-1, 1992.
Jensen JC, Pass HI, Sindelar WF, et al.: Recurrent or metastatic disease in select patients with adrenocortical carcinoma. Aggressive resection vs chemotherapy. Arch Surg 126 (4): 457-61, 1991.
Decker RA, Elson P, Hogan TF, et al.: Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma. Surgery 110 (6): 1006-13, 1991.
Bukowski RM, Wolfe M, Levine HS, et al.: Phase II trial of mitotane and cisplatin in patients with adrenal carcinoma: a Southwest Oncology Group study. J Clin Oncol 11 (1): 161-5, 1993.
Hesketh PJ, McCaffrey RP, Finkel HE, et al.: Cisplatin-based treatment of adrenocortical carcinoma. Cancer Treat Rep 71 (2): 222-4, 1987.
Schlumberger M, Ostronoff M, Bellaiche M, et al.: 5-Fluorouracil, doxorubicin, and cisplatin regimen in adrenal cortical carcinoma. Cancer 61 (8): 1492-4, 1988.
Berruti A, Terzolo M, Sperone P, et al.: Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer 12 (3): 657-66, 2005.
Top
More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Top
This information is provided by the National Cancer Institute.
This information was last updated on May 16, 2008.