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Incidence and Mortality
Adrenocortical carcinoma (ACC) is a rare tumor that affects only 0.72 persons per one million population. Although it mainly occurs in adults, children can be affected, too. The median age at diagnosis is 46 years. Historically, only about 30% of these malignancies are confined to the adrenal gland at the time of diagnosis. However, recently, more ACCs have been diagnosed at early states, most likely due to the widespread use of high-quality imaging techniques.
Retrospective studies have identified the following three important prognostic factors:
Patients who have low-grade tumors without evidence of invasion into local tissues or spread to lymph nodes have an improved prognosis. The role of other prognostic indicators is controversial.
In approximately 60% of patients, symptoms related to excessive hormone secretion are the main reasons for seeking medical attention. Biochemical hormone testing reveals that up to 80% of tumors are functioning. The second most common symptoms at time of initial presentation are unspecific abdominal symptoms, such as abdominal pain or fullness. A small percentage of ACCs is incidentally discovered by imaging studies conducted for reasons other than potential adrenal disease.
Initial evaluation should include careful endocrine studies to reveal any excessive hormone production by the tumor, which can serve as a tumor marker during therapy. Staging should include imaging of the primary site by computed tomography (CT) and/or magnetic resonance imaging of the abdomen. In addition, a CT of the chest is necessary to assess potential lung metastasis. Although the use of positron emission tomography may be effective in identifying unsuspected sites of metastases, its role as a staging tool is unclear. The detection of metastatic lesions may allow effective palliation of both functioning and nonfunctioning lesions.
Prognosis and Survival
The most common sites of metastases are the lung, liver, peritoneum, and less commonly, the bones and major veins. 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 adrenolytic therapy with mitotane antihormonal drugs (i.e., ketoconazole and metyrapone), systemic chemotherapy, and/or radiation therapy. However, 5-year survival for patients with stage IV tumors is usually less than 20%.
Although several studies have shown partial or even complete remission, there is no convincing evidence to date that systemic therapy will improve the survival duration of patients with adrenal cancer. Radical open 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 is approximately 38% to 46%.[1,2]
Adrenocortical carcinoma (ACC) can be classified into functioning and nonfunctioning tumors by clinical and biochemical assessment. Approximately 60% of ACCs produce hormones. The associated clinical syndromes include the following:
Biochemical assessment aims to detect increased levels of cortisol (24-hour urine, 1 mg dexamethasone suppression test, serum adrenocorticotropic hormone and cortisol), androgens (dehydroepiandrosterone sulfate, testosterone), estrogens (estradiol) and mineralocorticoids (renin, aldosterone).
Pathology can differentiate high-grade and low-grade tumors according to the mitotic activity of the tumor. The differentiation of benign and malignant adrenocortical tumors can be achieved by determination of the Weiss score, which scores several histopathological criteria, including the following:
Several staging systems for adrenocortical carcinoma (ACC) are in use. The American Joint Committee on Cancer (AJCC) staging system for  is based on the following assessment:
The stage of ACC 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. Proper staging should include computed tomography (CT) of the abdomen and chest. Magnetic resonance imaging (MRI) may add specificity to CT evaluation of an adrenal mass. In-phase and out-of-phase T1-weighted imaging may be the most effective noninvasive method to differentiate benign from malignant adrenal masses. MRI may suggest 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.
In addition to the above-mentioned AJCC staging, the European Network for the Study of Adrenal Tumors (ENSAT) staging system is widely used internationally. The ENSAT staging system is essentially the same as the AJCC system, but reserves stage IV only for tumors with distant metastasis. Other staging systems include the classical Macfarlane system, modified by Sullivan, and the Union Internationale Contre le Cancer staging system, published by the World Health Organization.
AJCC Stage Groupings and TNM Definitions
The AJCC has designated staging by TNM (tumor, node, metastasis) to define ACC.
Standard treatment options for stage I adrenocortical carcinoma (ACC)
Standard treatment options for stage I ACC include the following:
Treatment options under clinical evaluation for stage I ACC:
Although adjuvant mitotane has shown some progression-free or disease-free survival advantage, no overall survival advantage has been demonstrated thus far.[1,2,3]
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Standard treatment options for stage II adrenocortical carcinoma (ACC)
Standard treatment options for stage II ACC include the following:
Treatment options under clinical evaluation for stage II ACC
Standard treatment options for stage III adrenocortical carcinoma (ACC)
Standard treatment options for stage III ACC include the following:
Treatment options under clinical evaluation for stage III ACC
Treatment options under clinical evaluation for stage III ACC include the following:
Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:
Furthermore, a substantial number of treated patients with functioning tumors will show diminution in hormone production. In cases of increased hormone production, antisteroidogenic drugs such as ketoconazole and metyrapone, and steroid receptor antagonists, such as spironolactone and mifepristone, should be considered.
The role of mitotane as adjuvant therapy after complete tumor resection is still a matter of debate but should be discussed with the patient. In the case of complete resection, the role for adjuvant mitotane and radiation therapy is the same as for stage I and stage II ACC.
Temporary palliation of disseminated adrenocortical carcinomas (ACCs) can sometimes be achieved with the chemotherapeutic agent mitotane. Although measurable partial remissions are unusual and are reported in only 20% to 30% of cases, palliation of hormone symptoms is commonly observed. 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 or with radiation therapy.[1,2]
Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:
Furthermore, a substantial number of treated patients with functioning tumors will show diminution in hormone production. In cases of increased hormone production, antisteroidogenic drugs, such as ketoconazole and metyrapone, and steroid receptor antagonists, such as spironolactone and mifepristone, should be considered.
Clinical trials are appropriate and should be considered whenever possible because phase I and II trials evaluate newer chemotherapeutic and biologic agents.
Standard treatment options for stage IV ACC
Standard treatment options for stage IV ACC include the following:
Treatment options under clinical evaluation for stage IV ACC
Treatment options under clinical evaluation for stage IV ACC include the following new agents for unresectable ACC:
Trials of other chemotherapy regimens are also ongoing.
The question of whether to further treat patients with adrenocortical carcinoma (ACC), and the selection of treatment to use, 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 or radiation therapy. Although patients with recurrent ACC cannot be considered curable, palliation of hormonal symptoms and occasional 5-year survivals can be achieved. Substantial morbidity, however, is associated with resection of these recurrent tumors.
Clinical trials are appropriate and should be considered whenever possible because phase I and II trials evaluate newer chemotherapeutic and biological agents.
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Stage Information for Adrenocortical Carcinoma
Editorial changes were made to this section.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adrenocortical carcinoma. It 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.
Reviewers and Updates
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PDQ® Adult Treatment Editorial Board. PDQ Adrenocortical Carcinoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/adrenocortical/hp/adrenocortical-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389393]
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Last Revised: 2018-10-19
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