Management of adrenocortical carcinoma

Abstract

Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Patients present with signs of steroid hormone excess (e.g. Cushing's syndrome, virilization) or an abdominal mass. Tumour size at presentation (mean diameter at diagnosis > 10 cm) is the most important indicator of malignancy. In addition, computed tomography (CT) typically demonstrates an inhomogeneous adrenal lesion with irregular margins and variable enhancement of solid components after intravenous contrast media. Magnetic resonance imaging (MRI) is equally effective as CT and is particularly helpful to visualize invasion into large vessels. Complete tumour removal (R0 resection) offers by far the best chance for long-term survival and therefore surgery is the treatment of choice in stage I-III ACC. Despite tumour resection for cure most patients will eventually develop local recurrence or distant metastases. Thus adjuvant treatment options need to be evaluated in high-risk patients (e.g. radiation therapy of the tumour bed and/or chemotherapy). In tumour recurrence re-operation should always be considered. In metastatic disease (stage IV ACC) not amenable to surgery mitotane (o,p'DDD) remains the first-line therapy. Drug monitoring is needed for effective treatment aiming at concentrations between 14 and 20 mg/l. Patients not responding to mitotane may benefit from cytotoxic chemotherapy (23% partial remissions, 4% complete remissions). Only large prospective multicentre trials comparing different treatment options will allow to make systematic progress in the management of ACC.

Cushing Syndrome Caused by Adrenocortical Tumors and Hyperplasias (Corticotropin- Independent Cushing Syndrome)

“…Malignant neoplasias of the adrenal cortex account for 0.05-0.2% of all cancers, with an approximate prevalence of two new cases per million of population per year; adrenal cancer occurs at all ages, from early infancy to the eighth decade of life [21,22]. A bimodal age distribution has been reported, with the first peak occurring before age of 5 years, and the second in the fourth to fifth decade.…”

Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial

“…ACC patients often present with clinical syndromes secondary to the production of corticosteroids, although some patients bear non-functioning neoplasms (Allolio et al 2004). The stage of the disease at diagnosis and complete surgical resection are recognized as the strongest predictors of long-term survival (Allolio et al 2004). In two large multicenter European series, it was found that approximately 20% of patients have metastatic disease at the time of presentation (Crucitti et al 1996, Icard et al 2001, one out of four patients is left with residual disease after operation and half of those who had an apparently radical resection eventually relapse, often with distant metastases (Crucitti et al 1996, Icard et al 2001.…”

“…ACC patients often present with clinical syndromes secondary to the production of corticosteroids, although some patients bear non-functioning neoplasms (Allolio et al 2004). The stage of the disease at diagnosis and complete surgical resection are recognized as the strongest predictors of long-term survival (Allolio et al 2004).…”

Immunohistochemistry of a Proliferation Marker Ki67/MIB1 in Adrenocortical Carcinomas: Ki67/MIB1 Labeling Index Is a Predictor for Recurrence of Adrenocortical Carcinomas

“…The prognosis of patients with ACC depends largely on surgical resectability [4]. An increasing number of adrenal tumors have been discovered because of technological advances in imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) [5], suggesting the possibility that an increasing number of smaller ACCs can be detected as adrenal incidentalomas.…”