No abstract

Adrenocortical carcinoma (ACC) is a devastating tumor for either patients or their families because of short life expectancy and severe impact on quality of life. Due to the rarity of ACC, with a reported annual incidence of 0.5-2 cases per million population, progress in the development of treatment options beyond surgery has been limited. Up to now, no personalized approach of ACC therapy has emerged, apart from plasma level -guided mitotane therapy, and no simple targetable molecular event has been identified from preclinical studies. Complete surgical removal of ACC is the only potentially curative approach and has the most important impact on patient's prognosis.Despite the limits of the available evidence, adjuvant mitotane therapy is currently recommended in many expert centers whenever the patients presents an elevated risk of recurrence. The management of patients with recurrent and metastatic disease is challenging and the prognosis if often poor.Mitotane monotherapy is indicated in the management of patients with a low tumor burden and/or more indolent disease while patients whose disease show an aggressive behavior need cytotoxic chemotherapy. The treatment of patients with advanced ACC may include loco-regional approaches such as surgery and radiofrequency ablation in addition to systemic therapies. The present review provides an updated overview of the management of ACC patients following surgery and of the management of ACC patients with advanced disease.

Adrenocortical carcinoma (ACC) is an aggressive cancer characterized by poor survival. Apart from radical surgery, there is a limited range of therapeutic options and mitotane remains the cornerstone of medical treatment of ACC in either adjuvant or palliative settings. The aim of adjuvant mitotane therapy is to reduce the risk of ACC recurrence following surgical removal of the tumor. Use of mitotane in an adjuvant setting is off-label, but the recent guidelines endorsed by the European Society of Endocrinology (ESE) and the European Network for the Study of Adrenal Tumors (ENSAT) recommend it in ACC patients at high risk of recurrence. The palliative use of mitotane for treatment of advanced ACC aims at controlling tumor progression and, when present, hormone secretion. In this clinical setting, mitotane is used in association with chemotherapy to treat the more aggressive forms, while mitotane monotherapy is reserved for less progressive ACC. Many years after its introduction in clinical practice, there are still uncertainties surrounding the use of this old drug and the derived benefits. Moreover, physicians who use mitotane should recognize and manage the systemic effects of the drug that need a complex supporting therapy.