Contemporary management of adrenocortical carcinoma: A narrative review

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy arising from the adrenal cortex, characterized by local invasion and frequent distant metastases. Tumor size is a key predictor of malignancy, with lesions larger than 4 cm carrying a high likelihood of being malignant. Subsets of ACCs are functional, secreting excess glucocorticoids, sex steroids, or mineralocorticoids, leading to characteristic clinical syndromes. Diagnosis is often delayed due to nonspecific presentations, and management remains challenging because of limited effective systemic therapies, high recurrence rates, and the rarity of the disease, which restricts large-scale clinical trials. This review provides an overview of the current strategies in the diagnosis, staging, and treatment of ACC, and discusses the evolving therapeutic modalities. A narrative literature review was conducted using relevant publications from PubMed, Scopus, and recent international guidelines. Data from key trials and consensus statements were incorporated. Complete surgical resection, which entails adrenalectomy with local lymph node dissection, is the mainstay of curative treatment. Adjuvant mitotane and radiation therapy are currently the cornerstone of treatment post-surgery in those with high-risk features. High-risk tumors are those with incomplete resection, high grade, and Ki67>10%. Studies are ongoing to determine the role of chemotherapy in the adjuvant setting. The etoposide-doxorubicin-cisplatin (EDP) regimen, combined with mitotane, is the current standard of care for advanced disease. New therapies targeting tumor genomics or the immune microenvironment are under investigation. Adrenocortical carcinoma management requires a multidisciplinary and individualized approach. Further research into molecular and immunotherapeutic strategies is needed to improve patient outcomes.