Abstract
Adrenocortical carcinoma is a very rare cancer that commonly presents with hormonal abnormalities or, more rarely, as an incidental finding of an adrenal mass. Following optimal surgical management, ideally in the form of open adrenalectomy, meta-analyses show that adjuvant mitotane significantly increases recurrence-free and overall survival (HR 0.62 and 0.69 respectively) and tumour bed radiotherapy reduces locoregional recurrence and overall survival for higher risk cancers by at least 40-50%. Those with recurrent or metastatic cancers can be considered for the combination of etoposide, doxorubicin, cisplatin and mitotane (EDP-M) on the basis of results of a single randomised trial. There are significant pharmacological interactions within this regime that have yet to be satisfactorily addressed. Patients of borderline performance status may be treated with various modifications of this regime. More recent approaches with immune checkpoint inhibitors (ICI) and targeted therapy (TT), either alone or in combination, show some promise, but progression-free survival for the majority of regimes does not exceed 6 months. Cabozantinib or lenvatinib alone or in combination, show the greatest promise with disease control rates of 50% or greater, and progression-free survival in excess of 6 months. Studies combining ICIs and TT as a means of overcoming the immunosuppressive environment are ongoing. There are several ongoing clinical trials in this area although only a small proportion of patients may be able to access these. Local therapies with radiotherapy, thermal ablation or arterial embolisation may be helpful for selected patients, particularly those with oligometastatic disease or those with symptomatic metastases.