Adrenocortical Carcinoma

Adrenocortical carcinomas (ACCs) are rare cancers with an incidence of one to two per million population. Although 60–70% of adult patients with ACC present with clinical findings of hormone excess, the disease is often diagnosed late and in advanced stage and 5-year survival is less than 15%. Computed tomography (CT) is widely used in the diagnosis and size and CT attenuation may help differentiation of benign from malignant lesions. The only definitive criterion for malignant adrenal tumors is the presence of local invasion or distant metastases. After complete hormonal assessment to determine the secretory activity of the tumor, complete surgical resection is the only potentially curative treatment. Surgery might also have a role in patients with advanced disease for debulking to control hormone hypersecretion. Adjuvant mitotane is recommended in patients at high risk of recurrence (intraoperative tumor spillage, high ki67 index, size >8 cm or invasion of tumor capsule or blood vessels) after surgery. Adjuvant radiotherapy may reduce local recurrence, particularly in patients with incompletely resected ACC. Mitotane is the treatment of choice in advanced disease. Response rates are higher when mitotane is used in combination with cytotoxic chemotherapy, and should be preferred if there is extensive, rapidly progressive, high-grade disease. Insulin-like growth factor type 2 inhibitors and vascular endothelial growth factor (VEGF) inhibitors showed limited efficacy. Recently immune checkpoint inhibitors either alone or in combination with other agents are being tested in clinical trials and results so far showed activity in a subgroup of patients. There is a huge unmet need in the treatment of this rare and aggressive disease and international collaboration is needed to design translational research and prospective clinical trials.