Contemporary management of adrenocortical carcinoma.

CONTEXT

Adrenocortical carcinoma (ACC) is a rare and typically aggressive malignancy. Available recommendations are based primarily on retrospective series or expert opinions, and only few prospective clinical studies have yet been published.

OBJECTIVE

To combine the available evidence for diagnostic work-up and treatment of ACC to a contemporary recommendation on the management of this disease.

EVIDENCE ACQUISITION

We conducted a systematic literature search for studies conducted on humans and published in English using the Medline/PubMed database up to 31 January 2011. In addition, we screened published abstracts at meetings and several Web sites for recommendations on ACC management.

EVIDENCE SYNTHESIS

In patients with suspected localised ACC, a thorough endocrine and imaging work-up is followed by complete (R0) resection of the tumour by an expert surgeon. In experienced hands, laparoscopic adrenalectomy is probably as effective and safe for localised and noninvasive ACC as open surgery. Most clinicians agree that mitotane should be used as adjuvant therapy in the majority of patients, as they have a high risk for recurrence. An international panel has suggested using tumour stage, resection status, and the proliferation marker Ki67 as guidance for or against adjuvant therapy. In patients with advanced disease at presentation or recurrence not amenable to complete resection, a surgical approach is frequently inadequate. In these cases, mitotane alone or in combination with cytotoxic drugs is the treatment of choice. The most promising regimens (etoposide, doxorubicin, cisplatin plus mitotane, and streptozotocin plus mitotane) are currently compared in an international phase 3 trial, and results should be available by the end of 2011. Several targeted therapies are under investigation and may lead to new treatment options. Management of endocrine manifestations with steroidogenesis inhibitors is required in patients suffering uncontrolled hormone excess.

CONCLUSIONS

Detailed recommendations are provided to guide the management of patients with ACC.