European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Abstract

Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

Early Postoperative Circulating miR-483-5p Is a Prognosis Marker for Adrenocortical Cancer

“…The main limitations of our study are the small size of the cohort and a single-center population. While the prognostic values of the ENSAT stage and Ki67 index have been largely validated for ACC management [16], we found here in this cohort that ENSAT stage II and III or Ki67 > 10% did not predict recurrence risk or death. This is likely due to the limited number of patients analyzed in this study.…”

Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series

“…An adjuvant treatment with mitotane is recommended. In patients with advanced disease, systemic chemotherapy with etoposide, doxorubicin and cisplatin is added [5].…”

Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells

“…Clinical manifestations of ACC can be consequences of adrenal hormone excess (functional tumors) or growing abdominal masses. Standard systemic therapies for patients with advanced ACC are mitotane and chemotherapy [2]. The dichlorodiphenyl trichloroethane derivative mitotane represents the only drug that has been approved for the treatment of ACC for many decades, although its mechanism of antineoplastic activity is not fully understood [3] Clinical evidence shows that the efficacy of mitotane is strictly dependent on the attainment and the maintenance over time of circulating blood levels within the 14-20 mg/dL range [2].…”

“…Standard systemic therapies for patients with advanced ACC are mitotane and chemotherapy [2]. The dichlorodiphenyl trichloroethane derivative mitotane represents the only drug that has been approved for the treatment of ACC for many decades, although its mechanism of antineoplastic activity is not fully understood [3] Clinical evidence shows that the efficacy of mitotane is strictly dependent on the attainment and the maintenance over time of circulating blood levels within the 14-20 mg/dL range [2]. Due to the pharmacokinetic characteristics of mitotane, this value is usually reached in about 2-3 months [4], and this long latency could impair, at least, in part, the efficacy of the treatment.…”