Spanish consensus on the diagnosis and management of adrenocortical carcinoma

Abstract

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an estimated incidence of 0.7-2 cases per million/year. The rarity of this disease, coupled with limited preclinical models and clinical trials, has hindered progress, resulting in poor outcomes, with a 5-year survival rate of approximately 35%. Currently, the only available curative treatment is complete surgical resection of the adrenal tumor. For unresectable or metastatic ACC, the current standard therapeutic modalities are mitotane, chemotherapy, radiotherapy and locoregional treatments; however, these are noncurative. Mitotane has an adrenolytic and anti-steroidogenic effect, and it is used in the adjuvant setting for high-risk patients, as systemic therapy for metastatic disease, and/or to control hormonal secretion. While key pathways in ACC pathogenesis have been identified as potential therapeutic targets, results with targeted therapies remain modest, showing that there is a clinical unmet need for novel treatments or new combinations of exiting drugs. Effective management requires a multidisciplinary team of experts to optimize outcomes for patients. This article presents a multidisciplinary consensus on the diagnosis, management, prognosis and follow-up of patients with ACC, and the approach to two special contexts, ACC in pregnant women and hormone-producing ACC. The consensus was coordinated by the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE), with contribution from experts from related societies including the Spanish Association of Surgeons (AEC), Spanish Society of Urology (AEU), Anatomic-Pathology (SEAP), Nuclear Medicine (SEMNIM), Medical Oncology (SEOM) and Radiotherapeutic Oncology (SEOR).

Keywords: ENSAT; adrenal tumor; adrenalectomy; adrenocortical carcinoma; mitotane.

Figure 1

Radiological features of an ACC. CT of the abdomen with intravenous iodinated contrast with abdominal acquisition in arterial and portal phases: solid left adrenal mass with heterogeneous enhancement (8.2 × 9 × 9.3 cm, CCxTxAP). It displaces the tail of the pancreas cranially and caudally to the ipsilateral kidney. It does not show macroscopic fat foci or calcifications. The findings suggest adrenal carcinoma or pheochromocytoma as the first possibility. Pathological retroperitoneal lymphadenopathy (left paraaortic and interaortocaval) and in the hepatic hilum.

Figure 2

Surgery in localized ACC (stage I–III ENSAT). ACC, adrenocortical carcinoma. *Adjuvant chemotherapy may be considered in selected patients with very high risk for recurrence.

Figure 3

Surgery in advanced ACC (stage IV ENSAT). ACC, adrenocortical carcinoma.

Figure 4

Comparison of response rates in non-randomized chemotherapy trials with and without mitotane in patients with ACC. A full color version of this figure available at https://doi.org/10.1530/ERC-25-0034.

Figure 5

Lollipop plot of clinical trials with immunotherapy. PFS, progression-free survival; OS, overall survival. A full color version of this figure available at https://doi.org/10.1530/ERC-25-0034.

Figure 6

Recommendations for ACC follow-up. Based on Fassnacht et al. (2010), (2018), Gaujoux & Brennan (2012). Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; FDG PET, fluorodeoxyglucose positron-emission tomography/computed tomography.